Vasoactive Intestinal Peptide Concentrations Research Articles

Динаміка показників нейровегетативної регуляції в дітей із рекурентними захворюваннями респіраторного тракту і зниженим функціональним резервом міокарда після реабілітаційної програми

Актуальність. Останнім часом проблеми з рівнем дитячого здоров’я викликають побоювання з боку як медичної, так і педагогічної громадськості. Інтенсивна програма шкільної освіти, високе інфекційне навантаження на організм молодшого школяра і підвищений інтерес до засобів масової електронної комунікації — все це призводить до напруження функціонування вегетативної нервової системи (ВНС) і, як результат, зниження функціонального резерву міокарда. У зв’язку з цим було запропоновано проведення оздоровчих літніх заходів, метою яких було надати відновлюваний вплив на функціонування ВНС і стан функціонального резерву міокарда молодшого школяра. Мета роботи: проаналізувати клінічну ефективність реабілітаційної програми в дітей із рекурентними захворюваннями респіраторного тракту і зниженим функціональним резервом міокарда. Матеріали та методи. 30 дітям раннього шкільного віку проведена протягом 1 літнього місяця реабілітаційна програма. Здійснена оцінка клінічної ефективності реабілітаційної програми за даними стану ВНС, показників активності регуляторних систем (ПАРС), рівнів концентрації нейротрансмітерів у сироватці крові. Проведено оцінку функціонального резерву міокарда. Результати. За підсумками реабілітаційної програми отримані вірогідні результати поліпшення функціонування ВНС: знизилися прояви симпатикотонії і зменшилася реєстрація порушеного ПАРС і зривів процесів адаптації (p < 0,05). Звертають на себе увагу статистично значуще зниження сироваткової концентрації субстанції Р і кінцевих стабільних метаболітів NO (KCM NO) і підвищення сироваткової концентрації вазоактивного інтестинального пептиду. Дана позитивна динаміка супроводжувалася значним зниженням реєстрації симпатикотонії, ригідного ритму, порушеного ПАРС, зриву процесів адаптації (p < 0,05). Проведена річна реабілітаційна програма привела до поліпшення результатів проби Руф’є на 4 бали порівняно з показниками наприкінці навчального року. Висновки. Здійснення реабілітаційної програми в дітей із рекурентними захворюваннями респіраторного тракту і зниженим функціональним резервом міокарда поліпшило показники функціонального стану ВНС і ПАРС. Поліпшення функціонального стану ВНС і ПАРС супроводжувалося: зниженням рівня концентрації субстанції Р, КСМ NO в сироватці крові та підвищенням вазоактивного інтестинального пептиду. Проведення оздоровчого курсу в дітей із рекурентними гострими респіраторними захворюваннями та зниженим функціональним резервом міокарда дозволило знизити показник проби Руф’є на 4 бали, що свідчить про підвищення функціонального резерву міокарда.

Neurotransmitter serum levels in children with recurrent upper respiratory tract infections

Background. Schoolchildren are prone to frequent respiratory tract diseases. In the structure of general morbidity, this pathology ranks first. Its prevalence is more than 60 %, which leads to frequent school absenteeism, lack of active games and outdoor walks. So, there is an increase in the amount of time that a child spent on means of mass electronic communication and electronic games, resulting in high affection and addiction, forming hypodynamia, which in aggregate has a negative impact on the regulatory systems functioning. Recurrent upper respiratory tract infections (URTI) contribute to the strain of neuro-endocrine-immune regulation, causing an imbalance of neuropeptides — mediators of neurogenic inflammation. The purpose of this work is to study the neurogenic inflammation parameters in schoolchildren with functional disorders of the cardiovascular system and recurrent respiratory tract diseases. Materials and methods. We surveyed 130 children with URTI aged 6 to 9 years in the somatic well-being period. The analysis of the contents of vasoactive intestinal peptide (VIP), substance P and final stable metabolites of nitric oxide (FSM NO) in serum was carried out. An increase in substance P level in children with recurrent URTI was found, which had statistically significant differences with the healthy children indices (p < 0.05). Results. It has been found that high concentration of substance P increases the risk of recurrent URTI. It has been proved that in children with recurrent URTI due to increased FSM NO serum content that has a pro-inflammatory orientation, there is an increased neurogenic inflammation activity. It was found that the reliable reduction in the content of VIP as an anti-inflammatory transmitter in children with recurrent URTI can not suppress the activity of neurogenic inflammation, resulting in its excessive stimulation. Conclusions. Children with recurrent URTI in the somatic well-being period have increased serum levels of substance Р and FSM NO. In the somatic well-being period in schoolchildren with recurrent URTI, a decrease in the concentration of anti-inflammatory neuropeptide VIP is observed.

Inulin and isomalto-oligosaccharide alleviate constipation and improve reproductive performance by modulating motility-related hormones, short-chain fatty acids, and feces microflora in pregnant sows.

Constipation in gestating and lactating sows is common and the inclusion of dietary fiber may help to alleviate this problem. We investigated the effects of inulin (INU) and isomalto-oligosaccharide (IMO), two sources of soluble dietary fiber, on gastrointestinal motility-related hormones, short-chain fatty acids (SCFA), fecal microflora, and reproductive performance in pregnant sows. On day 64 of gestation, 30 sows were randomly divided into three groups and fed as follows: a basal diet, a basal diet with 0.5% INU, and a basal diet with 0.5% IMO. We found that INU and IMO significantly modulated the levels of gastrointestinal motility-related hormones, as evidenced by an increase in substance P (P < 0.05), and a decrease in the vasoactive intestinal peptide concentrations (P < 0.05), indicating the capacity of INU and IMO to alleviate constipation. Furthermore, IMO enhanced the concentrations of acetic, propionic, isobutyric, butyric, isovaleric, and valeric acids in the feces (P < 0.05). High-throughput sequencing showed that IMO and INU increased the fecal microflora α- and β-diversity (P < 0.05). Methanobrevibacter was more abundant (P < 0.05), whereas the richness of Turicibacter was lower in the INU and IMO groups than in the control group (P < 0.05). In addition, IMO significantly increased litter size (P < 0.05). Overall, our findings indicate that INU and IMO can relieve constipation, optimize intestinal flora, and promote reproductive performance in pregnant sows.

VIP reduction in the pancreas of F508del homozygous CF mice and early signs of Cystic Fibrosis Related Diabetes (CFRD)

Vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide with potent anti-inflammatory, bronchodilatory and immunomodulatory functions, is secreted by intrinsic neurons innervating all exocrine glands, including the pancreas, in which it exerts a regulatory function in the secretion of insulin and glucagon. Cystic fibrosis-related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF), impacting approximately 50% of adult patients. We recently demonstrated a 50% reduction of VIP abundance in the lungs, duodenum and sweat glands of C57Bl/6 CF mice homozygous for the F508del-CFTR disease-causing mutation. VIP deficiency resulted from a reduction in VIPergic and cholinergic innervation, starting before signs of CF disease were observed. As VIP functions as a neuromodulator with insulinotropic effect on pancreatic beta cells, we sought to study changes in VIP in the pancreas of CF mice. Our goal was to examine VIP content and VIPergic innervation in the pancreas of 8- and 17-week-old F508del-CFTR homozygous mice and to determine whether changes in VIP levels would contribute to CFRD development. Our data showed that a decreased amount of VIP and reduced innervation are found in CF mice pancreas, and that these mice also exhibited reduced insulin secretion, up-regulation of glucagon production and high random blood glucose levels compared to same-age wild-type mice. We propose that low level of VIP, due to reduced innervation of the CF pancreas and starting at an early disease stage, contributes to changes in insulin and glucagon secretion that can lead to CFRD development.

Attenuated serum vasoactive intestinal peptide concentrations are correlated with disease severity of non-traumatic osteonecrosis of femoral head

Background and objectiveThe neuropeptide vasoactive intestinal peptide is a 28-amino acid neuropeptide that has been shown to stimulate bone repair and angiogenesis. The purpose of this study was to explore the potential role of serum VIP concentration in osteonecrosis of femoral trauma (ONFH).MethodsOne hundred five patients diagnosed with non-traumatic ONFH and 103 healthy individuals were enrolled in our study. Serum VIP, tumor necrosis factor-α (TNF-α), interluekin-1 beta (IL-1β), and macrophage colony-stimulating factor (M-CSF) levels also were detected using the commercial ELISA kit. Radiographic progression was evaluated using FICAT classification. The clinical severity of ONFH was assessed by visual analog score (VAS) and Harris Hip Score (HHS). Receiver-operating characteristic (ROC) curve was performed to test the potential diagnostic value of VIP in radiographic progression.ResultsThe serum VIP level of patients with non-traumatic ONFH was significantly lower than that of healthy controls. There was no significant difference between the alcohol group, the steroid-induction group, and the idiopathic group. Serum VIP levels were significantly higher in ONFH patients with femoral head pre-collapse stage than collapse stage. Serum VIP levels were significantly lower. FICAT 4 non-traumatic ONFH patients had significantly lower serum concentrations of VIP when compared with FICAT 3 and FICAT 2. Moreover, serum VIP levels were significantly lower in ONFH patients with FICAT 3 than FICAT 2. Serum VIP levels were negatively related to FICAT stage. In addition, serum VIP levels were negatively associated with VAS score and positively associated with HHS score. Last, we found serum VIP levels were negatively associated with serum TNF-α and IL-1β levels. ROC curve analysis indicated that decreased serum VIP could serve as a decent biomarker with regard to the diagnosis of radiographic progression.ConclusionAttenuated serum VIP concentrations are correlated with disease severity of non-traumatic ONFH. Decreased serum VIP may serve as a potential indicator of non-traumatic ONFH.

Adoption of computerized tomography images in detection of lung nodules and analysis of neuropeptide correlative substances under deep learning algorithm

To solve the problems of low sensitivity and high false positive rate of current lung nodule detection technology, and to explore the correlation between neuropeptide correlative substances and lung nodules, in the study, the deep learning-based computerized tomography (CT) images were used to detect lung nodules. Specifically, a multi-scale three-dimensional convolutional neural network (CNN) was established for lung nodule detection. First, high-quality candidate nodules were obtained by a two-dimensional CNN. Then, three-dimensional CNNs of different scales were constructed for candidate nodules of different sizes, and the fused model was used to classify candidate nodules. Finally, the detection results of the single network, the two-dimensional CNN, and the fused network were compared. Meanwhile, the serum levels of vasoactive intestinal peptide (VIP) and substance P (SP) were detected in patients with lung injury caused by lung nodules, so as to analyze the correlation between neuropeptide correlative substances and lung nodules. The results showed that the detection sensitivity of the fused network was 85.8% and 92.9% when the number of false positives was 1 and 4, respectively, which were higher than that of the single network and two-dimensional CNN. However, the content of VIP in the serum of patients with pulmonary nodules was significantly reduced, while the content of SP was significantly increased. Therefore, the algorithm proposed in this study can effectively improve the sensitivity of the pulmonary nodule detection system and reduce false positive rate; at the same time, neuropeptide correlative substances may be correlated with the lung injury caused by pulmonary nodules.

Vasoactive intestinal peptide in canine portosystemic shunt in the absence of portal hypertension

Background:The congenital portosystemic shunt (PSS) is a common vascular anomaly in dogs. Vasoactive intestinal peptide (VIP) is produced in various organs (including the small intestine, large intestine, and pancreas), leading to abdominal vasodilation, increased blood flow, increased pancreatic blood flow, and promotion of pancreatic endocrine and exocrine secretions. However, there have been no reports on the concentration of VIP in the portal and peripheral veins in canine PSS.Aim:The aim of this pilot study was to evaluate whether dogs with PSS have a different VIP concentration in their portal system in general.Methods:Six dogs with an extrahepatic portosplenic shunt were included in the study. Blood samples were taken from the saphenous and portal veins during PSS ligation surgery with an amerid constrictor, to evaluate and compare the VIP concentration in both samples. VIP was measured using a commercial canine enzyme-linked immunosorbent assay kit.Results:The breeds included Mongrels (n = 2), Norfolk Terriers (n = 1), Miniature Dachshunds (n = 1), and Maltese (n = 2), and their ages were 9.3 ± 6.5 months; the bodyweight was 3.3 ± 0.8 kg. The concentration of VIP in the saphenous vein was 17.75 ± 13.88 pg/ml; on the contrary, the concentration of VIP in the portal vein was 29.7 ± 20.29 pg/ml. There was no significant difference in the VIP concentration between veins.Conclusion:There was no difference in the VIP concentration between the portal and saphenous veins, suggesting a non-association between VIP and the PSS, in the absence of portal hypertension.

Vasoactive Intestinal Peptide Changes the Frequency and Force of Myocardial Contraction in Rats.

We studied the effect of non-selective agonist of VIP receptors of vasoactive intestinal polypeptide in different concentrations on the frequency, force, and duration of isometric contraction of myocardial strips of the right atrium under conditions of spontaneous activity, as well as the force and duration of contractions of the right ventricle in rats. It was found that the agonist produced a positive inotropic and chronotropic effect that depended on its concentration. The maximum effect was observed at vasoactive intestinal peptide concentration of 10-11 M.

Effects of ethyl acetate extract of Salsola collina on brain-gut peptides and interstitial cells of gastric Cajal in rats with diabetic gastroparesis.

Objective(s):Effects of ethyl acetate extract of Salsola collina (EES) on brain-gut peptides and interstitial cells of gastric Cajal in rats with diabetic gastroparesis were explored. Materials and Methods:Rats were divided into six groups: normal control group (NC), diabetic gastroparesis model group (DGP), low, medium, and high dose of EES groups (LES, MES, and HES, respectively), and metoclopramide positive group (MPG). DGP rats were induced by streptozotocin (STZ) combined with a high-sugar-high-fat diet. The gastric emptying was measured by the phenol red labeling method. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the concentrations of serum ghrelin, gastrin (GAS), somatostatin (SS), and vasoactive intestinal peptide (VIP). The expressions of c-Kit and its natural ligand stem cell factor (SCF) in gastric tissues were determined by Western blot and immunofluorescence. Results:Gastric emptying rate increased in a different degree after intervention by EES, among which MES and HES groups showed a significant effect (compared with DGP, P<0.01) and the HES group was equivalent to the MPG group; serum ghrelin and content of serum GAS increased while SS and VIP decreased (compared with the DGP group, P<0.05 or P<0.01); c-Kit and SCF protein expressions in gastric tissue increased (compared with DGP group, P<0.05 or P<0.01). Conclusion:EES significantly improved gastric emptying by regulating gastrointestinal hormone excretion and c-Kit/SCF signaling pathway. Our study provides a pharmacological basis for the use of the EES in the treatment of DGP. However, the detailed molecular mechanism remains to be clarified.

Total glucosides of paeony (TGP) alleviates constipation and intestinal inflammation in mice induced by Sjögren's syndrome

Ethnopharmacological relevanceSjögren's syndrome (SS) is an autoimmune disease and can cause gastrointestinal disorders such as constipation and intestinal inflammation. As a kind of medicinal material, Paeonia lactiflora Pall has a variety of pharmacological effects, and it is also an indispensable component in many pharmaceutical preparations, which has been widely concerned by the medical and pharmaceutical circles. Total glucosides of paeony (TGP) is a mixture of biologically active compounds extracted from the root of Paeonia lactiflora Pall and has therapeutic effects on a variety of autoimmune diseases. Aim of the studyTo investigate the therapeutic effect of TGP on constipation and intestinal inflammation in mice modeled by SS, and to provide a basis for clinical research. Materials and methodsThe SS model was set up by submandibular gland (SMG) immune induction method and then treated with TGP for 24 weeks. The fecal characteristics were observed and the fecal number and moisture content were measured. Colonic pathology was observed by H&E staining. The levels of serum P substance (SP), vasoactive intestinal peptide (VIP), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, nitric oxide (NO), and nitric oxide synthase (NOS) were determined by enzyme linked immunosorbent assay (ELISA) and microplate method, respectively. Reverse transcription polymerase chain reaction (RT-PCR) was employed to analyze the mRNA expression of c-kit and stem cell factor (SCF) in colon. ResultsCompared with the model group, the dry and rough condition of the feces was improved, and the fecal gloss, number and moisture content significantly increased after the administration of TGP capsules. Meanwhile, TGP treatment improved colonic pathological damage, inhibited the serum concentrations of NO, NOS, IL-1β, TNF-α, NF-κB and SP, increased serum VIP concentration, and up-regulated mRNA expression of SCF and c-kit in colon. ConclusionsTGP could obviously attenuate SS-mediated constipation and intestinal inflammation in mice by acting on some intestinal motility related factors and inflammatory factors.

Pituitary adenylate cyclase activating polypeptide concentrations in the sheep mammary gland, milk, and in the lamb blood plasma after suckling.

Pituitary adenylate cyclase activating polypeptide (PACAP) is involved in development and reproduction. We previously described elevated PACAP levels in the milk compared to the plasma, and the presence of its specific PAC1 receptor in the mammary gland. This study aimed to determine PACAP and vasoactive intestinal peptide (VIP) levels in female suckling lambs compared to ewe plasma and mammary gland, as well as their age-dependent alterations. mRNA expressions of PACAP, VIP, PAC1 receptor and brain-derived neurotrophic factor (BDNF) were quantified in the milk whey and mammary gland. PACAP38-like immunoreactivity (PACAP38-LI) was measured in plasma, milk whey and mammary gland by radioimmunoassay, VIP-LI by enzyme-linked immunoassay. PACAP38-LI was 5, 6 times higher in the milk compared to the plasma of lactating sheep. It significantly increased in the lamb plasma 1 h, but returned to basal level 2 h after suckling. However, VIP mRNA was not present in the mammary gland, we detected the VIP protein in the milk whey. BDNF mRNA significantly decreased with age to approximately 60% and 25% in the 3- and 10-year-old sheep respectively, compared to the 3-month-old lambs. No differences were found between mammary and jugular vein plasma PACAP and VIP concentrations, or during the daily cycle. We propose a rapid absorption of PACAP38 from the milk and/or its release in suckling lambs. PACAP accumulated in the milk might be synthesized in the mammary gland or secreted from the plasma of the mothers. PACAP is suggested to have differentiation/proliferation promoting and immunomodulatory effects in the newborns and/or a local function in the mammary gland.

Effect of moxibustion on respiratory function and cutaneous histamine and neuropeptide contents of "Feishu" (BL13) in asthmatic rats

To observe the effect of moxibustion on respiratory function and contents of histamine and neuropeptides in skin tissue of "Feishu" (BL13) in asthmatic rats, so as to explore its mechanisms underlying improvement of asthma. Thirty-six SD rats were randomly divided into normal control, model and moxibustion groups, with 12 rats in each group. The asthma model was established by subcutaneous injection (at the back and groin, 0.5 mL) and i．p. injection (1 mL)of mixture solution of ovalbumin (OVA), Aluminium Hydroxide gel and 0.9% sodium chloride solution, and repeated nasal drip of 1% OVA. Moxibustion was applied to bilateral BL13 for 15 min, once daily for 14 days. The inspiratory and expiratory resistance, and pulmonary ventilation compliance were detected by using a small animal pulmonary function tester under anesthesia. The contents of histamine, vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in the local skin tissue of the left BL13 were assayed by using enzyme-linked immunosorbent assay (ELISA). After modeling, the inspiratory and expiratory resistance were significantly increased (P<0.01), and the lung ventilation compliance was significantly decreased in the model group relevant to the normal control group (P<0.01). Outcomes of ELISA showed that the content of VIP was significantly lower (P<0.01), and those of histamine, SP and CGRP in the skin of left BL13 were significantly increased in the model group relevant to the normal control group (P<0.01). Following the intervention, the inspiratory and expiratory resis-tance, cutaneous histamine, SP and CGRP contents were significantly decreased (P<0.01), while the lung ventilation compliance and cutaneous VIP level were significantly increased in the moxibustion group in contrast to the model group (P<0.01, P<0.05). Moxibustion of BL13 can improve pulmonary function in asthma rats, which may be related to changes of levels of histamine and neuropeptides as VIP, SP and CGRP in the local skin tissues of BL13.

Maillard Reaction Products of Stir Fried Hordei Fructus Germinatus Are Important for Its Efficacy in Treating Functional Dyspepsia.

Hordei Fructus Germinatus (HFG) has been used as a traditional medicine to treat functional dyspepsia (FD) in China. Stir fried HFG (F-HFG) containing Maillard reaction products (MRPs) is used more widely than the raw HFG (R-HFG). However, the exact mechanisms in its functionality remain unclear. This article investigated the effect of R-HFG, F-HFG, and MRPs on brain-gut peptides, gut microbiota, and digestive enzymes using an FD animal mode. After administration of R-HFG, F-HFG, and MRPs, higher mRNA expression level of gastrin (GAS) and lower mRNA expression level of vasoactive intestinal peptide (VIP) were exhibited in F-HFG and MRPs rats than R-HFG rats (P < .05). Furthermore, compared with the R-HFG group, the contents of motilin (MTL) and GAS showed an upward tendency, whereas the contents of VIP and chokcystokinin (CCK) showed a downward tendency in the F-HFG group. In addition, bacterial communities in the control, F-HFG, and MRPs groups clustered closely to one another, and bacterial communities in the model and recovery groups clustered together, whereas the bacterial communities in the R-HFG group were clustered into a category. Moreover, there were no apparent differences in brain-gut peptides and gut microbiota between the F-HFG and MRPs groups. However, after the oral administration of R-HFG, F-HFG, and MRPs, the level of digestive enzyme did not show a significant change as compared with the recovery group. These results indicated that the stronger effect of F-HFG could be attributed to the MRPs produced during stir frying, and MRPs possessed the effect of regulating brain-gut peptides and gut microbiota.

Effect of Artemisia rupestris L. Extract on Gastrointestinal Hormones and Brain-Gut Peptides in Functional Dyspepsia Rats.

Artemisia rupestris L. is the perennial herb of rupestris belonging to Artemisia (Compositae), which is wildly distributed in Xinjiang (China), middle Asia, and Europe. It is known to have anti-inflammatory, hepatoprotective, immune function regulation, and gastrointestinal function regulation effects. AR is used to treat digestive diseases, but the effects of AR on antifunctional dyspepsia (FD) activity have not yet been reported. In this study, we aimed to investigate the therapeutic effects of Artemisia rupestris L. extract (ARE) on gastrointestinal hormones and brain-gut peptide in functional dyspepsia (FD) rats. Sixty Sprague-Dawley rats were randomly divided into 6 groups. An FD rat model was established by irregular tail clamp stimulation for 14 days except the blank group. After FD rat models, the blank group and model group were given menstruum, and the medicated rats were given corresponding medicine for 14 days. The general observations, bodyweight, and food intake were observed, and the content of serum gastrin (GAS), plasma motilin (MTL), plasma vasoactive intestinal peptide (VIP), and plasma somatostatin (SS) by the enzyme-linked immunosorbent assay was observed. The content of plasma VIP and plasma SS in the ARE group was significantly lower than in the model group, and the content of serum GAS and plasma MTL was increased in the ARE group; the GAS expression of antrum and hypothalamus was increased in the ARE group, and SS expression of antrum and hypothalamus was decreased in the ARE group by immunohistochemical detection; the results of semiquantitative reverse transcription polymerase chain reaction (RT-PCR) indicate that ARE inhibits the mRNA expression of VIP. Our results suggest that ARE can recover gastrointestinal hormone levels and regulation of the peripheral and central nervous system and alter gut peptide levels, which confirm the therapeutic effect of ARE on functional dyspepsia.

Metabolomic study of raw and bran-fried Atractylodis Rhizoma on rats with spleen deficiency

Atractylodis Rhizoma, a classical Chinese medicine, exhibits unambiguous therapeutic effect on spleen deficiency in China for decades. The aim of the present study was to explore the different effects on the composition and level of endogenous metabolites in rats with spleen deficiency after oral administration of raw and bran-fired Atractylodis Rhizoma, and to explain the mechanism of pharmacodynamic enhancement of the bran-fried Atractylodis Rhizoma from the perspective of metabolomics. With this purpose, spleen deficiency model was established by diet, excessive fatigue and bitter cold diarrhea. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of vasoactive intestinal peptide (VIP), Somatostatin (SS), substance P (SP) and succinodehydrogenase (SDH) in rats of each group, and to compare the contents of VIP, SS, SP and SDH among groups. UHPLC-Q-TOF-MS based metabolomics was adopted to analyze the plasma from spleen deficiency rats and control rats. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the control group and the model group；The OPLS-DA were used to analyze the effects of raw and bran-fried Atractylodis Rhizoma on the same metabolites. The results showed that compared with the control group, the contents of VIP, SS, SP and SDH in the plasma of model group decreased, which proved the success of the model group. Compared with model group, the contents of VIP, SS, SP and SDH in the plasma of raw and bran-fried Atractylodis Rhizoma increased, and the effect of bran-fried Atractylodis Rhizoma was better than that of raw Atractylodis Rhizoma. Metabolomics results showed that seventeen different metabolites of spleen deficiency were screened out in the plasma of rats with spleen deficiency compared with the control group. Among them, Nicotinic acid, Dihydrofolic acid, Pantetheine 4′-phosphate and Photophatidylcholine (PC) were the metabolites significantly associated with spleen deficiency, and bran-fried Atractylodis Rhizoma had better intervention and regulation. Through the analysis of metabolic pathways related to these different metabolites of spleen deficiency, and primarily involved in glucosamine metabolism, one carbon pool by folate and so on. This study showed that Atractylodis Rhizoma could provide satisfactory therapeutic effects on spleen deficiency and metabolomics study can be utilized to further understand the molecular mechanisms.

Changes in plasma levels of cholecystokinin, neurotensin, VIP and PYY in gastric and colorectal cancer – Preliminary results

Physiological roles of enterohormones such as secretion, absorption and digestion were supported by clinical data. Overexpression of cholecystokinin (CCK), neurotensin (NT) and vasoactive intestinal peptide (VIP) receptors occur in gastrointestinal (GI) malignancies. The aim of the paper was to compare plasma levels of CCK, peptide YY (PYY), VIP and NT in patients with gastrointestinal malignancies and healthy controls. The study included 80 patients (37 men and 43 women) with GI malignancies (20 with gastric and 60 with colorectal cancers). Median age of the patients was 62.9 years (range: 40–85 years). Control group was comprised of 30 healthy persons with median age 59.8 years (range: 40–82 years). Fasting plasma concentrations of CKK, PYY, NT, and VIP were determined at rest, using ELISA kits for automated systems. Comparative analysis of enterohormone levels in patients with various types of gastrointestinal malignancies demonstrated presence of some cancer-specific alterations. Patients with gastric cancers presented with lower plasma concentrations of CCK than healthy controls and individuals from colorectal cancers (p = 0.02). The highest plasma concentrations of neurotensin was found in colorectal cancer patients in comparison to gastric (p = 0.02). The plasma levels of VIP observed in gastric cancer group were lower than in colorectal cancer patients (p = 0.01). Patients with GI malignancies may present with tumor-specific alterations in plasma enterohormone levels.

Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat

Congestive cardiac failure has become one of the major health challenges of the 21st century and new therapies are needed to address this problem. The concentration of vasoactive intestinal peptide (VIP) in the heart has been shown to decrease as fibrosis (the pathology leading to heart failure) increases and to become undetectable in end stage cardiomyopathy. We sought to determine whether replenishment of myocardial VIP might treat myocardial fibrosis and therefore represent a new therapeutic target.Wistar Kyoto rats on a high (4.4%) salt diet were randomised to zero time control, 4 week infusion of VIP (5 pmol/kg/min) or vehicle control infusion. Myocardial VIP concentration was measured by radioimmunoassay, fibrosis was quantitated by computerised histomorphometry and changes in pro-fibrotic mediators were measured by quantitative rt-PCR.Myocardial VIP increased significantly in VIP treated rats compared with vehicle treated controls (P < 0.01) while fibrosis in the VIP treated rats was significantly lower than in both the zero time control (P < 0.05) and the vehicle infused control (P < 0.0005). Although all six profibrotic mediators which were measured increased over the 4 week experimental period VIP infusion only affected angiotensinogen (Agt) and angiotensin receptor type 1a (AT1a) expression. In both instances VIP caused a significant decrease in messenger rna expression (Agt P < 0.01 and At1a P < 0.01) compared with vehicle infused controls.We conclude that VIP infusion increased myocardial VIP concentration and was able to reverse existing myocardial fibrosis suggesting a possible therapeutic role for a VIP based therapy in cardiac failure.

Efficacy of High Specific Volume Polysaccharide - A New Type of Dietary Fiber - On Molecular Mechanism of Intestinal Water Metabolism in Rats With Constipation.

BackgroundThe aim of this study was to evaluate the effects of a new type of dietary fiber – high specific volume polysaccharide (HSVP) – on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway.Marerial/MethodsCompound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression.ResultsThe constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression.ConclusionsHSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.

The Neuropeptide Vasoactive Intestinal Peptide Levels in Serum are Inversely Related to Disease Severity of Postmenopausal Osteoporosis: A Cross-Sectional Study.

Background: The neuropeptide vasoactive intestinal peptide (VIP) has been identified as inhibiting osteoclastogenesis and suppressing inflammation. Objective: This study was conducted to examine serum VIP levels in postmenopausal osteoporosis (PMOP) patients and explore the correlation of serum VIP levels with disease severity of PMOP. Methods: A total of 106 postmenopausal women diagnosed as osteoporotic were enrolled in the study and 102 postmenopausal women with normal bone mineral density (BMD) were enrolled as controls. BMD at the femoral neck (FN), lumbar spine 1-4, and total hip were examined using dual-energy X-ray absorptiometry. Genant semiquantitative grading was used for vertebral morphometry and fracture. Serum VIP levels were tested using enzyme-linked immunosorbent assay. Serum inflammatory factor interleukin-1β (IL-1β), osteoclastic activity marker tartrate-resistant acid phosphatase 5b (TRACP-5b), and estrogen-2 (E2) were also examined. Receiver operating characteristic (ROC) analyses was performed to determine the diagnostic values of serum VIP, IL-1β, TRCAP-5, and E2 with regard to Genant grade. Results: Our findings demonstrated a reduction in the serum level of VIP expressed in PMOP patients compared with controls. In the PMOP group, patients with lumbar fracture had significantly lower serum VIP concentrations in comparison with healthy controls. Serum VIP concentrations were positively associated with BMD at the FN, lumbar spine 1-4, and total hip. We also observed that serum VIP levels were positively correlated with E2 levels but negatively correlated with IL-1β and TRCAP-5 levels. In addition, ROC analysis found that reduction of serum VIP in combination with elevation of TRACP-5b may serve as an indicator of a severe Genant grade. Conclusions: Attenuated serum VIP levels were linked to disease severity of PMOP and may act as a protective marker for PMOP.

A17270 He neuroendocrine peculiarities of essential arterial hypertension development

Objectives: To investigate the potential role of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) in the pathogenesis of essential arterial hypertension (EAH). Methods: 25 patients with I-III stages of EAH and 14 practically healthy volunteers aged from 22 to 70 years were examined. The content of VIP and NPY in the blood plasma was determined by immuno-enzymatic methods using the Bachem Peninsula Laboratories, Inc. sets. Results: We found a significant initial decrease in the levels of NPY in the plasma of all the examined patients with EAH. Depending on stage of the disease, it was shown that as EAH progressed, the plasma NPY level decreased from 1,532 ± 0,386 ng/ml to 1,054 ± 0,148 ng/ml. Level of activity of NPY was found to be inversely proportional to the degree of BP increase. Consequently, a decrease in the level of NPY stipulates higher figures of BP in patients with EAH, contributing to the further progression of the disease. However, the activity of this neuropeptide in plasma of patients with stage II was comparable to that of healthy volunteers and was 0,843 ± 0,191 ng/ml, which was significantly higher than in patients with stage III (0,404 ± 0,043 ng/ml). That is, in the course of hypertension, compensatory normalization of VIP activity was observed at the stage of development of lesions of target organs, with the depletion of which irreversible disturbances of their function develop. The content of VIP in patients with “moderate” arterial hypertension (0,393 ± 0,057 ng/ml) was significantly lower than in healthy volunteers. Conclusion: We detected a dynamic decrease in the activity of NPY and VIP in patients with EAH which indicates the involvement of these regulatory peptides in the development of arterial hypertension.