Rate In Rats Research Articles

Effect of superfine pulverization on physicochemical and medicinal properties of Qili Powder

Qili Powder, a preparation from Traditional Chinese Medicine, commonly used to treat in-juries from falling or stumbling, pain caused by bruising, and traumatic hemorrhage. The aim of the present work was to investigate the application of the superfine pulverization on Qili Powder properties. The physicochemical and medicinal properties of fine Qili Powder with D90 particle size of 164.5μm, and superfine Qili Powder with D90 particle size of 32.2μm were investigated. The results showed that with decreasing particle size, the specific surface area and pore volume increased, the fluidity decreased, and the percentage of moisture absorption and the balanced moisture content decreased. Analysis HPLC, XRD and FTIR results indicated that superfine pulverization didn’t influence dracorhodin content, nor the molecular structure and crystal form of Qili Powder. The percentage of dissolution of dracorhodin was significantly improved after superfine pulverization. Pharmacokinetics results confirmed that superfine pulverization increases the absorption rate in rats and dracorhodin content of Qili Powder.

Hyaluronic acid-coated solid lipid nanoparticles for targeted delivery of vorinostat to CD44 overexpressing cancer cells

Hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) were developed for tumor-targeted delivery of vorinostat (VRS), a histone deacetylase inhibitor. HA, a naturally occurring polysaccharide, which specifically binds to the CD44 receptor, was coated on a cationic lipid core through electrostatic interaction. After the optimization process, HA-coated VRS-loaded SLNs (HA-VRS-SLNs) were spherical, core-shell nanoparticles, with small size (∼100nm), negative charge (∼−9mV), and narrow size distribution. In vitro release profile of HA-VRS-SLNs showed a typical bi-phasic pattern. In addition, the intracellular uptake of HA-VRS-SLNs was significantly enhanced in CD44 overexpressing cells, A549 and SCC-7 cells, but reduced when HA-VRS-SLNs were incubated with SCC-7 cells pretreated with HA or MCF-7 cells with low over-expressed CD44. Of particular importance, HA-VRS-SLNs were more cytotoxic than the free drug and VRS-SLNs in A549 and SCC-7 cells. In addition, HA shell provided longer blood circulation and reduced VRS clearance rate in rats, resulting in enhanced higher plasma concentration and bioavailability. These results clearly indicated the potential of the HA-functionalized lipid nanoparticle as a nano-sized drug formulation for chemotherapy.

The intraspecies relationship between tissue turnover and metabolic rate in rats

AbstractEcologists interested in studying fluctuating relationships between consumers and nutrient sources are increasingly involved in modeling the rate at which consumers incorporate dietary components. In mammals a correlation between resting metabolic rate (RMR) and tissue turnover may exist across a range of species. Less is known about the variation of tissue turnover rate within a species, and how that correlates with RMR. Here we examine two strains of rats (Rattus norvegicus) with different RMR to test whether variation in RMR is positively correlated with tissue turnover rate within a species. If RMR, a relatively simple measurement, can be correlated with tissue turnover, then this relationship could be used to better interpret ecological functions, including impact of migratory or seasonally available nutrient sources. Here, the changing isotope signature in rat whole blood was modeled using a modified exponential decay equation and a reaction progress variable model. The modeled rate of turnover, metabolic rate (O2 consumed), and mass were then compared between strains of rats. The mass and RMRs (conditions during which RMRs were determined modified from the ideal, as outlined in the Methods) were significantly different between strains, but half‐life and the metabolic tissue replacement component of turnover (as opposed to turnover from mass gain) were not. No significant correlation was found between RMR and metabolic tissue replacement between the strains. Results suggest that within a species showing a range of RMRs, blood tissue turnover should not vary significantly.

Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in rats with fulminant hepatic failure

The mechanism of renal failure during fulminant hepatic failure (FHF) or end-stage of liver disease is not fully understood. The present study aims to delineate the mechanisms of decreased glomerular filtration rate (GFR) in acute hepatic failure. A rat model of renal insufficiency in severe liver injury was established by lipopolysaccharide (LPS) plus D-galactosamine (GalN) exposure. GFR was evaluated by continuous infusion of fluorescein isothiocyanate–inulin with implanted micro-osmotic pumps. GalN/LPS intoxication resulted in severe hepatocyte toxicity as evidenced by liver histology and biochemical tests, whereas renal morphology remained normal. GFR was reduced by 33% of the controls 12 h after GalN/LPS exposure, accompanied with a decreased serum sodium levels, a marked increase in serum TNF-α and ET-1 levels as well as significantly upregulated renal type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression. The upregulated IP3R1 expression was abrogated by the treatment of anti-TNF-α antibodies, but not by 2-aminoethoxydiphenylborate (2-APB), which blocks the inositol 1,4,5-trisphosphate signaling pathway. Treatments with either TNF-α antibodies or 2-APB also significantly improved the compromised GFR, elevated serum urea nitrogen and creatinine levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. The extent of acute liver injury as reflected by serum ALT levels was much more attenuated by anti-TNF-α antibodies than by 2-APB. Liver histology further confirmed that anti-TNF-α antibodies conferred better protection than 2-APB in GalN/LPS-exposed rats. LPS-elicited TNF-α over-production is responsible for decreased GFR through IP3R1 overexpression, and the compromised GFR resulted in the development of acute renal failure in rats with FHF.

Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine.

It has been demonstrated that carbon nanotubes (CNTs) associated with sodium hyaluronate (HY-CNTs) accelerate bone repair in the tooth sockets of rats. Before clinical application of HY-CNTs, it is important to assess their biocompatibility. Moreover, cardiac toxicity may be caused by the translocation of these particles to the blood stream. The aim of this study was to evaluate possible changes in cardiovascular function in male Wistar rats whose tooth sockets were treated with either CNTs or HY-CNTs (100 μg/mL, 0.1 mL). Blood pressure and heart rate were monitored in conscious rats 7 days after treatment. Cardiac function was evaluated using the Langendorff perfusion technique. The data showed no changes in blood pressure or heart rate in rats treated with either CNTs or HY-CNTs, and no significant changes in cardiac function were found in any of the groups. To confirm these findings, experiments were conducted in rats injected intraperitoneally with a high concentration of either CNTs or HY-CNTs (0.75 mg/kg). The same parameters were analyzed and similar results were observed. The results obtained 7 days following injection indicate that the administration of low concentrations of CNTs or HY-CNTs directly into tooth sockets did not cause any significant change in cardiovascular function in the rats. The present findings support the possibility of using these biocomposites in humans.

C9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway

Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis9,trans11 (9,11-CLA) and trans10,cis12 (10,12-CLA) isomers enhanced the antioxidant/detoxifying mechanism via the activation of nuclear factor E2-related factor-2 (Nrf2) and improved mitochondrial function, but less is known about the actions of specific isomers. The differential ability of individual CLA isomers to modulate these pathways was explored in Wistar rats fed for 4 weeks with a lard-based high-fat diet (L) or with control diet (CD), and, within each dietary treatment, two subgroups were daily administered with 9,11-CLA or 10,12-CLA (30 mg/day). The 9,11-CLA, but not 10,12-CLA, supplementation to CD rats improves the GSH/GSSG ratio in the liver, mitochondrial functions, and Nrf2 activity. Histological examination reveals a reduction of steatosis in L-fed rats supplemented with both CLA isomers, but 9,11-CLA downregulated plasma concentrations of proinflammatory markers, mitochondrial dysfunction, and oxidative stress markers in liver more efficiently than in 10,12-CLA treatment. The present study demonstrates the higher protective effect of 9,11-CLA against diet-induced pro-oxidant and proinflammatory signs and suggests that these effects are determined, at least in part, by its ability to activate the Nrf2 pathway and to improve the mitochondrial functioning and biogenesis.

Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats.

The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents.

Influence neurotransplantation on the enzymatic activity of cells of the cerebral cortex of rats resuscitated different gender and age (729.1)

The objectives of the research included:Study the comparative aspects of the dynamics of enzyme activity of the cerebral cortex reanimated rats of different age and sex using fetal nerve cells;Experiments have been performed on 43 rats of both sex, who turned 1,5 months and 12 months by the research beginning. A 4 minute clinical death from acute mechanical asphyxia was simulated. At the time of cardiac activity restoration we performed intraperitoneal injection of fetal cells of the nervous tissue in a dose of 1mm per 25g of the animal. Repeated injection of the cells was carried out on 14th day of the postresuscitational period. The rate of rats’ survival was determined in the postresuscitational period. For the purposes of research of the kinetics of enzymatic reactions in the homogenate of the cerebral cortex the content of the following enzymes was determined (Tell L.Z.): lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase, cholinesterase (ChE). As a result of the single neurotransplantation the males has improvement in an enzymatic activity of the cerebral cortex, whereas enzymatic activity of the females get worse. Repeated neurotransplantation is accompanied by reduction in activity Che in young reanimated males, young females have declined enzymatic activity of LDH and increase ‐ CK. In adult females, along with decreased activity of creatine kinase increases the enzymatic activity cholinesterase.

Vagal modulation of resting heart rate in rats: the role of stress, psychosocial factors, and physical exercise

In humans, there are large individual differences in the levels of vagal modulation of resting heart rate (HR). High levels are a recognized index of cardiac health, whereas low levels are considered an important risk factor for cardiovascular morbidity and mortality. Several factors are thought to contribute significantly to this inter-individual variability. While regular physical exercise seems to induce an increase in resting vagal tone, chronic life stress, and psychosocial factors such as negative moods and personality traits appear associated with vagal withdrawal. Preclinical research has been attempting to clarify such relationships and to provide insights into the neurobiological mechanisms underlying vagal tone impairment/enhancement. This paper focuses on rat studies that have explored the effects of stress, psychosocial factors and physical exercise on vagal modulation of resting HR. Results are discussed with regard to: (i) individual differences in resting vagal tone, cardiac stress reactivity and arrhythmia vulnerability; (ii) elucidation of the neurobiological determinants of resting vagal tone.

STUDY CARDIOTOXIC PROPERTIES OF NATIVE PEAT HUMIC ACIDS

The earlier pathomorphological studies of toxic properties of peat humic acids (PHAs) at intraperitoneal injection revealed that one of the causes of lethality is the direct cardiotoxic action of PHAs. For the further study of the mechanism of cardiotoxic action, electrocardiogram was recorded and ventricular fibrillation threshold was determined in male rats after intraperitoneal injection of humic acids in knowingly lethal dose – 480 mg/kg bwt. A single intraperitoneal injection of PHA to rats in knowingly lethal dose caused a significant decrease of the ventricular fibrillation threshold in comparison with intact animals. It was found that the PHA injection exerted no significant effect on the heart rate in rats and change of the PQ, QT, and QTc intervals. At the same time, the significant shortening of the QRS complex in comparison with intact animals was observed. Judging from the results obtained, the single injection of humic acids in the lethal dose induced a decrease in the electrical stability of heart, as evidenced by the drop of the ventricular fibrillation threshold. This decrease of the electrical stability of heart can be a cause of sudden cardiac death of trial rats. Disorder of the heart electrical stability is likely connected with the ionophoric action of humic acids and change of electrophysiological properties of cell membranes.

Evaluation of attenuated Salmonella choleraesuis-mediated inhibin recombinant DNA vaccine in rats.

DNA vaccination has been studied intensively as a potential vaccine technology. We evaluated the effect of an attenuated Salmonella choleraesuis-mediated inhibin DNA vaccine in rats. First, 15 rats were treated with different doses of an inhibin vaccine to evaluate vaccine safety. Next, 30 rats were divided into 3 groups and injected intramuscularly with the inhibin vaccine two (T1) or three times (T2) or with control bacteria (Con) at 4-week intervals. The inhibin antibody levels increased [positive/negative well (P/N) value: T1 vs Con = 2.39 ± 0.01 vs 1.08 ± 0.1; T2 vs Con = 2.36 ± 0.1 vs 1.08 ± 0.1, P < 0.05] at week 2 and were maintained at a high level in T1 and T2 until week 8, although a small decrease in T2 was observed at week 10. Rats in the T1 group showed more corpora lutea compared with the Con group (10.50 ± 0.87 vs 7.4 ± 0.51, P < 0.05). Estradiol (0.439 ± 0.052 vs 0.719 ± 0.063 ng/mL, P < 0.05) and progesterone (1.315 ± 0.2 vs 0.737 ± 0.11 ng/mL, P < 0.05) levels differed significantly at metestrus after week 10 between rats in the T1 and Con groups. However, there were no significant differences in body, ovary, uterus weights, or pathological signs in the ovaries after immunization, indicating that this vaccine is safe. In conclusion, the attenuated S. choleraesuis-mediated inhibin vaccine may be an alternative to naked inhibin plasmids for stimulating ovarian follicular development to increase the ovulation rate in rats.

Intravital Video Microscopy Measurements of Retinal Blood Flow in Mice

Alterations in retinal blood flow can contribute to, or be a consequence of, ocular disease and visual dysfunction. Therefore, quantitation of altered perfusion can aid research into the mechanisms of retinal pathologies. Intravital video microscopy of fluorescent tracers can be used to measure vascular diameters and bloodstream velocities of the retinal vasculature, specifically the arterioles branching from the central retinal artery and of the venules leading into the central retinal vein. Blood flow rates can be calculated from the diameters and velocities, with the summation of arteriolar flow, and separately venular flow, providing values of total retinal blood flow. This paper and associated video describe the methods for applying this technique to mice, which includes 1) the preparation of the eye for intravital microscopy of the anesthetized animal, 2) the intravenous infusion of fluorescent microspheres to measure bloodstream velocity, 3) the intravenous infusion of a high molecular weight fluorescent dextran, to aid the microscopic visualization of the retinal microvasculature, 4) the use of a digital microscope camera to obtain videos of the perfused retina, and 5) the use of image processing software to analyze the video. The same techniques can be used for measuring retinal blood flow rates in rats.

Intravital Video Microscopy Measurements of Retinal Blood Flow in Mice

Alterations in retinal blood flow can contribute to, or be a consequence of, ocular disease and visual dysfunction. Therefore, quantitation of altered perfusion can aid research into the mechanisms of retinal pathologies. Intravital video microscopy of fluorescent tracers can be used to measure vascular diameters and bloodstream velocities of the retinal vasculature, specifically the arterioles branching from the central retinal artery and of the venules leading into the central retinal vein. Blood flow rates can be calculated from the diameters and velocities, with the summation of arteriolar flow, and separately venular flow, providing values of total retinal blood flow. This paper and associated video describe the methods for applying this technique to mice, which includes 1) the preparation of the eye for intravital microscopy of the anesthetized animal, 2) the intravenous infusion of fluorescent microspheres to measure bloodstream velocity, 3) the intravenous infusion of a high molecular weight fluorescent dextran, to aid the microscopic visualization of the retinal microvasculature, 4) the use of a digital microscope camera to obtain videos of the perfused retina, and 5) the use of image processing software to analyze the video. The same techniques can be used for measuring retinal blood flow rates in rats.

Abstract 84: Effects of Edaravone on Brain Apoptotic Gene in CA/CPR Rats

Edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one), a strong novel free radical scavenger, is used in clinically as a novel neuroprotective agent for the treatment of patients with acute ischemic stroke. We assessed the hypothesis that the neuroprotective effect of edaravone corresponding with brain apoptosis could improvethe survival outcomes in a rat model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Adult male Sprague-Dawley rats were divided into saline, edaravone groupssubjected to sham group (sham surgery, n=10), saline group (CA for 5 min following CPR and intravenous ejection of saline 1.5 ml/kg, n=20), edaravone (CA for 5 min following CPR and intravenous ejection of edaravone 3 mg/kg, n=20)groups. The resuscitated animals were observed for 72 h after the restoration of spontaneous circulation. The rat survival time, survival rate was assessed and the expression of caspase-3, caspase-8, Bax and Bcl-2mRNA at 12, 24, 48 and 72 hours in hippocampus was measured by real time-PCR. Edaravone markedly enhanced the survival time and rate of rats (Kaplan-Meier analysis) after CA/CPR compared to saline group [(70.00±26.69) h, 95% CI (17.67-122.33)] vs[(23.00±3.91) h, 95% CI (15.33-30.67)] and (45% vs. 25%, χ2=4.900, P=0.027). The expression of apoptotic gene mRNA was significant upregulation (except caspase-8 and Bax in edaravone group at 72 h) in both the saline and edaravone groups (P&lt;0.05) compared to sham group. Edaravone significantly decreased the expression of caspase-3, caspase-8 and Bax mRNA (P&lt;0.05) and facilitate Bcl-2 expression (P&lt;0.05) compared to saline group (Tab1-4). This study suggests that (i)CA/CPR results in upregulation of pro-and anti-apoptosis; (ii)edaravone suppresses the up-regulation of the pro-apoptotic gene expression and facilitates the expression of anti-apoptotic gene in the hippocampus, involved in the improvement of the survival outcomes after CPR.

The long-term effects of phase advance shifts of photoperiod on cardiovascular parameters as measured by radiotelemetry in rats

Cardiovascular parameters, such as blood pressure and heart rate, exhibit both circadian and ultradian rhythms which are important for the adequate functioning of the system. For a better understanding of possible negative effects of chronodisruption on the cardiovascular system we studied circadian and ultradian rhythms of blood pressure and heart rate in rats exposed to repeated 8 h phase advance shifts of photoperiod. The experiment lasted 12 weeks, with three shifts per week. Spectral power as a function of frequency for both circadian and harmonic ultradian rhythms was expressed as the circadian–ultradian power ratio. The circadian rhythms of blood pressure, heart rate and locomotor activity were recorded during the control light:dark (LD) regimen with higher values during the D in comparison with the L. Phase advance shifts resulted in a diminished circadian–ultradian power ratio for blood pressure, heart rate and locomotor activity indicating suppressed circadian control of these traits greater in heart rate than blood pressure. In conclusion, rats kept under irregular LD conditions have suppressed circadian control of heart rate, blood pressure and locomotor activity and rely more on an acute response to the LD regime. Their ability to anticipate regular loads can be weakened and in this way chronodisruption can contribute to the pathogenesis of cardiovascular diseases.

Effects of electrical stimulation of autonomic nerves to the ovary on the ovarian testosterone secretion rate in rats

Previously, we demonstrated that electrical stimulation of the superior ovarian nerve (SON), but not the ovarian nerve plexus (ONP), reduces the secretion rate of estradiol from the ovary via activation of alpha 2-adrenoceptors in rats. The inhibitory effect of SON on estradiol secretion may be due to reduced production of testosterone, a direct precursor of estradiol. Here, we examined the effects of electrical stimulation of the SON and the ONP on ovarian testosterone secretion in rats. On the day of estrous, ovarian venous blood samples were collected intermittently from the ovarian vein. The secretion rate of testosterone from the ovary was calculated from the difference in the testosterone concentration between ovarian venous plasma and systemic arterial blood plasma, and the rate of ovarian venous plasma flow. Stimulation of either the SON or ONP reduced the secretion rate of testosterone from the ovary. The reduction of the testosterone secretion rate by SON stimulation was not influenced by an alpha 2-adrenoceptor antagonist (yohimbine), but it was abolished by an alpha 1-adrenoceptor antagonist (prazosin). Our results show that ovarian nerves have an inhibitory role in ovarian testosterone secretion, via activation of alpha 1-adrenoceptors, but not alpha 2-adrenoceptors. This, therefore, indicates that the reduction of estradiol secretion by SON stimulation is independent of the reduction of testosterone secretion.

Reflex modulation of ovarian estradiol secretion via the superior ovarian nerve by somatosensory stimulation in rats

Our previous study demonstrated that electrical stimulation of the superior ovarian nerve in rats reduces the ovarian estradiol secretion rate. In the present study, we examined the effect of noxious mechanical afferent stimulation (pinching) of a hindpaw on the ovarian estradiol secretion rate in rats. The rats were anesthetized on the day of estrus, and the ovarian venous blood was collected intermittently. The secretion rate of estradiol from the ovary was calculated from differences in the estradiol concentration between ovarian venous plasma and systemic arterial blood plasma, and from the flow rate of ovarian venous plasma.

Naringin Exhibits in vivo Prokinetic Activity via Activation of Ghrelin Receptor in Gastrointestinal Motility Dysfunction Rats

Background and Purpose: Poncirus fructus (PF), also known as the dried immature fruit of Poncirus trifoliata (L.) Raf., has long been used as a cure for the treatment of various gastrointestinal disorders in eastern Asia. Recently, it was reported that naringin, a flavonoid constituent of the PF extract, causes the activation of ghrelin receptor in vitro. Although the ghrelin receptor is involved in the enhancement of intestinal motility, there are no studies as yet involving in vivo action of naringin. Therefore, the purpose of the present study is to investigate whether naringin exhibits a prokinetic effect in vivo. Methods: We measured the intestinal transit rate in rats with gastrointestinal motility dysfunction (GMD) and performed a pharmacokinetic analysis of naringin to investigate the effect of naringin on prokinetic activity in vivo. Results: The results of this study show that the aqueous extract of PF and its constituent naringin have a strong prokinetic activity in GMD rats via activation of the ghrelin receptor. Surprisingly, pharmacokinetic analysis revealed that naringin has low bioavailability (11%), implying that the prokinetic effect of naringin was largely due to the local activation of ghrelin receptor in the intestine rather than a systemic effect after absorption. Indeed, it turned out that intravenous administration of naringin led to a lower prokinetic effect than when administrated orally to rats, indicating that naringin prefers to act on the intestinal wall rather than getting absorbed into the systemic circuit. This local mode of action might be advantageous for preventing possible systemic side effects since naringin is not well absorbed into the system circuit. Conclusions: Naringin exhibits an in vivo prokinetic activity by a preferable local activation of ghrelin receptor. Moreover, we propose that naringin could play a role as a leading compound for the development of ghrelin receptor-based prokinetic agents.

Effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) pretreatment on septic rats

To evaluate the effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) injection on the survival rate of rats post cecal ligation and puncture (CLP), Sprague-Dawley (SD) rats were subcutaneously injected with 0.125 ml, 0.25 ml or 0.5 ml PA-MSHA for 8 days or 16 days before CLP. The survival rate and physiological appearance of rats in each group were monitored daily post CLP. The expression of Toll-like receptor 4 (TLR4) and cytokines related to inflammation was evaluated. We found that the 0.5 ml-8d (0.5 ml PA-MSHA injected for 8 days) group had the highest 7-day survival rate (91.7%), which was significantly improved compared with the CLP-only group (33.3%). Furthermore, our results showed that PA-MSHA effectively increased serum pro-inflammatory mediators (TNF-α, IL-1β and IL-6) at the early stage (8 days) but increased anti-inflammatory mediators (IL-4 and IL-10) at the late stage (16 days). PA-MSHA significantly up-regulated the mRNA expression of TLR4 at 8 and 16 days. After PA-MSHA pretreatment, CLP had no marked effect on the levels of most inflammatory factors. To explore potential protective mechanisms of PA-MSHA against CLP, we examined the effect of PA-MSHA on murine macrophage-like RAW264.7 cells and found that PA-MSHA induced endotoxin tolerance. In conclusion, this study suggested that precisely controlling the dosage and time of PA-MSHA administration can effectively increase the rat survival rate post CLP, which may be mediated through regulating inflammatory mediators and inducing endotoxin tolerance.

Pyruvate Ringer's Solution Corrects Lactic Acidosis and Prolongs Survival during Hemorrhagic Shock in Rats

BackgroundLactic acidosis is a life-threatening complication of hemorrhagic shock. There is no ideal therapy for it in the clinical setting. ObjectiveThis study was designed to investigate whether pyruvate Ringer's solution could treat hypoxic lactic acidosis associated with lethal hemorrhagic shock in rats. MethodsA total of 54 rats were subjected to hemorrhagic shock with mean arterial pressure (MAP) of 40 mm Hg for 1 h. They were then randomly divided into three groups (n = 18 each): Group N had no fluid resuscitation; Group L received lactated Ringer's solution infusion; and Group P received pyruvate Ringer's solution infusion. The survival rate was investigated after 24 h. In addition, a second set of 54 rats was selected for blood sampling, with identical methods for shock and resuscitation being followed, to determine arterial pH, blood gas analysis, lactate, pyruvate, and organs' enzyme activities at various time points. The MAP was monitored for 6 h in both populations. ResultsPyruvate Ringer's solution significantly increased the survival rate of rats subjected to fatal shock and receiving pyruvate Ringer's solution (Group P) by 1.5 times the survival rate in Group L at 24 h after fluid resuscitation (55.6% vs. 22.2%, respectively; p < 0.05). Pyruvate infusion maintained a higher MAP and fully corrected severe acidosis 1 h after resuscitation in comparison to the lactated infusion, and markedly decreased blood lactate levels and the lactate-to-pyruvate ratio 4 h after resuscitation. It also significantly improved serum markers of organ dysfunction. ConclusionPyruvate Ringer's solution efficiently treated hypoxic lactic acidosis and significantly increased the survival rate in rats with lethal hemorrhagic shock. Pyruvate Ringer's solution is potentially applicable to clinical resuscitation in humans.