Rat Model Of Syndrome Research Articles

Calycosin ameliorates albuminuria in nephrotic syndrome by targeting Notch1/Snail pathway

BackgroundHeavy proteinuria is an important hallmark for kidney disease including nephrotic syndrome. Astragali Radix, a traditional Chinese herb, holds the potential to alleviate nephrotic syndrome; however, the underlying mechanism has not been completely clarified. The study aimed to explore the role of calycosin (C16H12O5), a major active component of Astragali Radix, in regulating adriamycin-induced proteinuria.MethodsA rat model of nephrotic syndrome was established through two adriamycin injections within two weeks (4 mg/kg for the first week and 2 mg/kg for the second week). After the induction of renal injury, 10 mg/kg or 20 mg/kg calycosin was intraperitoneally injected into rats for four weeks. Before euthanasia of rats, urine and blood samples were collected, and body weight was recorded. Then, 24 h urine protein content, kidney index, total cholesterol (TC), triglyceride (TG), as well as renal function indicators including blood urea nitrogen (BUN), serum creatinine (SCR), and urine albumin excretory rate (UAE) were measured. Hematoxylin-eosin staining for renal cortex tissues was performed to evaluate glomerular structural damage. TUNEL assay was performed to evaluate renal cell apoptosis. Western blotting was conducted to measure protein levels of podocyte-specific markers (podocin and nephrin), Notch1, and Snail in rat renal tissues.ResultsCalycosin reversed adriamycin-induced increase in proteinuria content, kidney index, and concentrations of renal function indicators. Calycosin ameliorated glomerular structural damage, inflammatory cell infiltration, and basement membrane thickening in model rats. In addition, calycosin rescued the suppressive impact of adriamycin on renal cell apoptosis and protein levels of podocyte markers. The activated Notch1/Snail signaling in model rats was suppressed by calycosin intervention.ConclusionCalycosin exerts a protective role against adriamycin-induced nephrotic syndrome via inhibition of the Notch1/Snail signaling.Clinical trial detailsNot applicable.

A blocking antibody against anti-Müllerian hormone restores ovulation and normal androgen levels in a spontaneous rat model of polycystic ovary syndrome.

A blocking antibody against anti-Müllerian hormone restores ovulation and normal androgen levels in a spontaneous rat model of polycystic ovary syndrome.

2062 A Rat Model of Second Impact Syndrome: Evidence of Facial Pain, Neurological Changes, and Tissue Alterations

2062 A Rat Model of Second Impact Syndrome: Evidence of Facial Pain, Neurological Changes, and Tissue Alterations

Resveratrol Protects Against Letrozole-Induced Renal Damage in a Rat Model of Polycystic Ovary Syndrome: A Biochemical, Histological, and Immunohistochemical Study

Resveratrol Protects Against Letrozole-Induced Renal Damage in a Rat Model of Polycystic Ovary Syndrome: A Biochemical, Histological, and Immunohistochemical Study

Protective Effects of Physalis angulata on Podocythopathies Through B-Cell-Activating Factor Inhibition in Doxorubicin-Induced Nephrotic Syndrome Rat Model.

Background/Objectives: Nephrotic syndrome, a glomerular disease caused by podocyte dysfunction, is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Current treatment relies on corticosteroids, which carry the risk of long-term side effects. Physalis angulata has potential as an adjunct therapy for immune-mediated kidney injury. This study aims to evaluate the effects of Physalis angulata extracts on anti-nephrin IgG, IL-4, and podocytopathy through BAFF inhibition in a doxorubicin-induced nephrotic syndrome rat model. Methods: This experimental study involved 36 Sprague-Dawley rats divided into control and treatment groups. The treatment groups received Physalis angulata extract at doses of 500 mg/kgBW, 1500 mg/kgBW, and 2500 mg/kgBW, or in combination with prednisone, alongside a group receiving prednisone monotherapy. Podocytopathy was assessed using proteinuria, nephrin, podocalyxin, and GLEPP-1. Proteinuria was measured using spectrophotometry. Serum BAFF levels, renal IL-4, urinary nephrin, and urinary podocalyxin were analyzed using ELISA. Renal nephrin, renal podocalyxin, GLEPP-1, and BAFF expression were evaluated by immunofluorescence microscopy. The data were analyzed using SPSS 25. Results: The results showed significant reductions in proteinuria, serum BAFF levels, renal BAFF expression, anti-nephrin IgG, IL-4, urinary nephrin, and urinary podocalyxin, along with significant increases in GLEPP-1, renal nephrin, and renal podocalyxin expression, in all treatment groups compared to the nephrotic syndrome control group. The combination of Physalis angulata at 2500 mg/kgBW with prednisone demonstrated the best effects. Conclusions: Physalis angulata shows promise as an adjuvant therapy for nephrotic syndrome by improving podocytopathy through BAFF inhibition. Further research is needed to evaluate its long-term safety, optimize dosing, and explore clinical applications in humans.

Effects of Lactococcus cremoris PS133 in 5-Hydroxytryptophan-Induced Irritable Bowel Syndrome Model Rats.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder marked by abdominal pain and irregular bowel habits. Recently, more and more evidence supports gut microbiota imbalance in IBS and highlights the potential of probiotics in restoring gut health and reducing symptoms. In this study, we explored the effects of Lactococcus cremoris PS133 (PS133) on an IBS-like condition in rats triggered by 5-hydroxytryptophan (5-HTP), a serotonin precursor. Eight-week-old Sprague Dawley rats received either PS133 or saline for 14 days, followed by 5-HTP to induce IBS-like symptoms. Colorectal distension tests showed that PS133 reduced visceral hypersensitivity. PS133 also protected intestinal mucin against 5-HTP-induced degradation, as seen in alcian blue staining, and increased the levels of tight junction proteins (occludin and zonula occludens-1) in the colon, indicating improved gut barrier integrity. Additionally, PS133 normalized the levels of substance P (a neuropeptide) in the spinal cord and altered 5-hydroxyindoleacetic acid (a serotonin metabolite) in the brain. Gut microbiota analysis revealed PS133 regulated specific bacterial groups, including [Eubacterium]_coprostanoligenes_group and Lactococcus. Overall, PS133 improved gut function, reduced IBS-like symptoms, and modulated gut microbiota, neurotransmitters, and intestinal barrier health in this IBS model.

The Effects of Methylprednisolone and Hyaluronic Acid on the Endometrium in Experimentally Induced Asherman Syndrome Rat Models: A Prospective Laboratory Study.

Background and Objectives: The current study was designed as a prospective laboratory investigation to evaluate the histopathological effects and VEGF (vascular endothelial growth factor) expression in uterine tissue following treatment with a combination of methylprednisolone and hyaluronic acid in a rat model of experimentally induced Asherman Syndrome. Materials and Methods: Twenty-six female Sprague-Dawley rats were used. Trichloroacetic acid was applied to the right uterine horns of all the groups to induce adhesion formation. First, we induced the Asherman model in two rats (Group 1). The remaining rats were divided into the following three groups: Group 2 received intrauterine hyaluronic acid treatment, Group 3 received oral methylprednisolone treatment, and Group 4 received both treatments. Inflammation, gland count, and fibrosis levels were assessed histopathologically. VEGF levels were analyzed immunohistochemically. Results: Hyaluronic acid treatment increased the uterine lumen diameter and vascularization. Methylprednisolone treatment increased the gland count and uterine wall thickness while decreasing the inflammation and fibrosis scores. Combined treatment provided a statistically significant advantage over single treatments. In particular, the combined treatment group exhibited significantly lower fibrosis (p = 0.184) and inflammation scores (p = 0.071), as well as higher gland counts (p = 0.849) and VEGF expression (p = 0.114), compared to the groups receiving only methylprednisolone or hyaluronic acid. These differences indicate that the synergistic effect of the two agents results in more effective endometrial healing than when either treatment is applied alone. Conclusions: Methylprednisolone treatment significantly prevented adhesion formation and reduced the inflammation and fibrosis scores compared to hyaluronic acid treatment alone. The combined treatment adds to the effects of the hyaluronic acid treatment alone and provides better healing.

Vitamin D and Dapagliflozin Alleviate Renal Injury and Insulin Resistance in a Diet-Induced Metabolic Syndrome Rat Model.

Metabolic syndrome, primarily driven by high-fat/high-sugar (HF/HS) diets, is closely linked to insulin resistance and renal injury, leading to serious complications such as type 2 diabetes mellitus and diabetic nephropathy. This study explored the combined effects of Vitamin D (VD) and dapagliflozin (Dap) on metabolic and renal complications in an HF/HS diet-induced rat model of metabolic syndrome. The combination therapy significantly improved insulin sensitivity, reduced fasting blood glucose levels, and alleviated renal injury markers such as blood urea nitrogen and creatinine. It also attenuated inflammation, lipid accumulation, and endoplasmic reticulum stress in renal tissues, as evidenced by reduced levels of inflammatory cytokines and key stress markers (GRP78 and CHOP). Importantly, the study highlights the novel synergistic potential of VD and Dap in addressing these complications through complementary mechanisms. These findings suggest that this combination therapy offers promising clinical potential for managing metabolic syndrome and its progression to severe complications.

Dissection of the Potential Activity Materials and Mechanism of Cortex Moutan Based on In Vivo Substances Profiling

ABSTRACTThis study aimed to identify the main chemical components of Moutan Cortex (MC) using Ultra‐High‐performance liquid chromatography and quadrupole time‐of‐flight (TOF) mass spectrometry and explore its therapeutic targets for hemorrhagic fever with renal syndrome complications through network pharmacology. A total of 28 compounds were identified in MC, including 7 gallic acylglucoses, 10 monoterpenoids, 6 paeonol compounds, 2 organic acids, and 3 flavonoids. In addition, after the rats ingested MC, six prototype substances were clearly identified in the rat plasma. Using VENNY and STRING databases, 161 intersection targets between MC and hemorrhagic fever with renal syndrome were identified, with key targets including VACM‐1, PIK3R1, PIK3CA, EGFR, MAPK1, TP53, and AKT1. These targets are involved in PI3K‐AKT and other signaling pathways, influencing cell survival, apoptosis, and inflammatory responses. Experimental validation showed that MC significantly reduced blood glucose, creatinine, and urea nitrogen levels in hemorrhagic fever with renal syndrome model rats and improved kidney function. Additionally, qRT‐PCR analysis demonstrated that high‐dose MC intervention effectively decreased the expression of VCAM‐1 and IL‐1β, both in serum and at the mRNA level in renal tissue, indicating its potent anti‐inflammatory effects. These findings suggest that MC exerts multifaceted therapeutic effects on HFRS through multicomponent, multitarget, and multipathway mechanisms, providing a theoretical basis for its clinical application.

Investigating the Effects of Chasteberry and Green Tea Extract on Polycystic Ovarian Syndrome Rat Models

Investigating the Effects of Chasteberry and Green Tea Extract on Polycystic Ovarian Syndrome Rat Models

A longitudinal rat forelimb model for assessing in vivo neuromuscular function following extremity reperfusion injury.

Rhabdomyolysis following revascularization of the ischemic upper extremity can lead to life- & limb-threatening sequelae. In the context of replantations and vascularized composite allografting, a reconstructive procedure usually reserved for upper limb amputees, prolonged tissue ischemia is detrimental to extremity functional recovery. Currently, validated survival small animal models of extremity reperfusion injury that permit longitudinal assessment of limb function are lacking. To date, studies that evaluated reperfusion injury-induced neuromuscular impairment rely on terminal ex vivo procedures and do not provide clinically translatable measurements. Furthermore, it is unclear if upper extremity musculature exhibits a different ischemic threshold compared to the lower limb given the relatively rare incidence of upper limb ischemia. Here, we present a reliable rat model of extremity post-reperfusion syndrome (PRS) that comprehensively recapitulates the biochemical hallmarks of rhabdomyolysis secondary to upper extremity reperfusion injury and allows for monitoring in vivo upper limb function using clinically relevant electrodiagnostic and kinematic metrics. In addition to inducing severe metabolic derangements, our forelimb PRS provided insights on gross motor and electrophysiological alterations upper-extremity reperfusion injury. We identify gait coordination parameters such as stride frequency and forelimb-hindlimb coordination index and electrophysiological metrics including compound muscle action potential amplitude as objective, non-invasive outcome measures for limb function assessment in small animal models of extremity PRS. This comprehensive, validated functional model can serve as an invaluable tool to evaluate therapeutics or preconditioning regimens to attenuate PRS and mitigate resulting neuromuscular dysfunction.

Assessing the therapeutic potential of Banana blossom extract in ameliorating Mifepristone-Induced Polycystic Ovarian Syndrome in Rat Model

Assessing the therapeutic potential of Banana blossom extract in ameliorating Mifepristone-Induced Polycystic Ovarian Syndrome in Rat Model

Docosahexaenoic and Eicosapentaenoic Acid Supplementation Could Attenuate Negative Effects of Maternal Metabolic Syndrome on Liver Lipid Metabolism and Liver Betacellulin Expression in Male and Female Rat Offspring.

Background/Objectives: This study investigated the effects of maternal metabolic syndrome during pregnancy on hepatic fatty acid metabolism and betacellulin expression in rat offspring. A rat model of maternal metabolic syndrome was created with a high-fructose diet (15% fructose in drinking water for six months). Methods: The females with metabolic syndrome were divided into the CON group, the HF group, which received fructose in drinking water, and the HF-DHA group, which received fructose in water and increased amounts of DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) in the diet (2.5% fish oil in the diet). The male and female offspring were killed at birth and their liver tissue was analyzed for the fatty acid profile and expression of Δ-9-desaturase and betacellulin. Results: When the rat offspring were exposed in utero to maternal fatty acids altered by the high-fructose diet, this resulted in a similarly altered fatty acid profile in the liver, with the most significant changes being Δ-9 desaturation and a dramatic increase in monounsaturated fatty acids. The offspring also showed an overexpression of hepatic betacellulin. Supplementation with DHA and EPA increased the DHA content and normalized the fatty acid composition of oleic acid, saturated fatty acids, linoleic acid and n3-docosapentaenoic acid in the offspring of mothers on a high-fructose diet. In addition, the DHA/EPA supplementation of fructose-fed mothers normalized hepatic Δ-9-desaturase and betacellulin overexpression in the offspring, suggesting that DHA/EPA supplementation affects not only the fatty acid content but also the liver function. Conclusions: The changes observed in this study suggest that DHA/EPA supplementation may modulate the effects of maternal programming on disorders of the lipid metabolism in the offspring.

Serum inflammation-related proteins in a acute compartment syndrome rat model

We aim to explore variations of serum inflammation-related proteins in an acute compartment syndrome (ACS) rat model. We collected serum from 25 healthy Sprague-Dawley rats (control group, CG) and 50 rats with tibial fractures, including 25 rats with ACS (ACS group, AG), and 25 rats without ACS (fracture group, FG). Ten samples per group were randomly chosen for proximity extension assay analysis of 92 inflammation-related proteins, and all samples were verified by enzyme-linked immunosorbent assays. Receiver-operating characteristic curve analysis was used to identify the diagnostic ability and cut-off values. Our findings showed that the levels of Il6 and Prdx5 in the FG and Il6, Prdx5, Dctn2, and Plin1 in the AG, were significantly higher than those in the CG. Notably, compared with the FG, high expression of Prdx5, Dctn2, and Plin1 was observed in the AG. Additionally, we identified 58.8764, 14.023, and 31.8730 pg/ml as the cut-off values of Prdx5, Dctn2, and Plin1 to predict ACS in rats. Similarly, the cut-off values of Il6, Prdx5, Dctn2, and Plin1 to predict ACS in healthy rats were 10.6783, 766.5879, 12.5627, and 14.3623 pg/ml, respectively. Furthermore, the combination of these proteins had the highest diagnostic accuracy. We identified Prdx5, Dctn2, and Plin1 as potential biomarkers of ACS compared with fracture in rats and revealed that combination of Il6, Prdx5, Dctn2, and Plin1 had the highest diagnostic accuracy to predict ACS compared with the healthy condition. Furthermore, the cut-off values for these biomarkers were determined, providing a new method to rapidly assess the risk of ACS and manage early targeted interventions.

Cardiomyocyte T-System Remodeling in a Rat Model of Metabolic Syndrome

Cardiomyocyte T-System Remodeling in a Rat Model of Metabolic Syndrome

Establishment and evaluation of a rat model of cervical spondylosis with Yin deficiency syndrome.

To establish and evaluate a rat model of cervical spondylosis (CS) with yin deficiency syndrome. Thirty-six male Sprague-Dawley rats were randomly assigned to the control group, CS group, and CS with Yin deficiency syndrome (YCS) group (n = 12 per group). The control group underwent daily routine care for 37 days. The CS group underwent induction of cervical static-dynamic imbalance, followed by 30 days of standard care. The YCS group underwent cervical static-dynamic imbalance induction, followed by 7 days of sleep deprivation to model Yin deficiency cervical spondylosis. Behavioral performance, heart rate, blood pressure, mechanical pain thresholds, serum cAMP, cGMP, cAMP/cGMP levels, and the expression of collagen-II, Bcl-2, Bax, and Bcl-2/Bax in cervical intervertebral discs were analyzed at various time points. Following CS induction, modeled rats exhibited significant changes in intervertebral disc structure, including misalignment of the annulus fibrosus, atrophy of the nucleus pulposus, rough cartilaginous endplate boundaries, and disc degeneration. Mechanical pain thresholds decreased. In the YCS group, compared with the CS and control groups, rats showed heightened excitability, dull fur, reddish mouth, lips, nose, paws, and tail, resistance to handling, slower weight gain, initial heart rate elevation followed by decline, and progressive blood pressure reduction. Serum cAMP and cAMP/cGMP ratios were significantly elevated, while cGMP levels were reduced. Collagen-II, Bcl-2, and Bcl-2/Bax levels decreased, and Bax levels increased. The established rat model of Yin deficiency syndrome aligns with clinical and traditional Chinese medicine characteristics, making it a promising model for studying Yin deficiency syndrome.

Targeting IL-20 alleviates inflammatory mechanical allodynia and reduces epidural fibrosis in post-laminectomy syndrome rat model.

Targeting IL-20 alleviates inflammatory mechanical allodynia and reduces epidural fibrosis in post-laminectomy syndrome rat model.

Adropin/Tirzepatide Combination Mitigates Cardiac Metabolic Aberrations in a Rat Model of Polycystic Ovarian Syndrome, Implicating the Role of the AKT/GSK3β/NF-κB/NLRP3 Pathway.

Polycystic ovarian syndrome (PCOS) is a multifaceted metabolic and hormonal disorder in females of reproductive age, frequently associated with cardiac disturbances. This research aimed to explore the protective potential of adropin and/or tirzepatide (Tirze) on cardiometabolic aberrations in the letrozole-induced PCOS model. Female Wistar non-pregnant rats were allotted into five groups: CON; PCOS; PCOS + adropin; PCOS + Tirze; and PCOS + adropin+ Tirze. The serum sex hormones, glucose, and lipid profiles were securitized. Cardiac phosphorylated levels of AKT(pAKT), glycogen synthase kinase-3 beta (pGSK-3β), NOD-like receptor family pyrin domain containing 3 (NLPR3), IL-1β and IL-18 were assayed. The cardiac redox status and endoplasmic reticulum stress (ER) parameters including relative glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) gene expressions were detected. Finally, the immunoreactivity of cardiac NF-κB, Bcl2, and BAX were assessed. Our results displayed that adropin and/or Tirze intervention successfully alleviated the PCOS-provoked cardiometabolic derangements with better results recorded for the combination treatment. The synergistic effect of adropin and Tirze is mostly mediated via activating the cardiac Akt, which dampens the GSK3β/NF-κB/NLRP3 signaling pathway, with a sequel of alleviating oxidative damage, inflammatory response, ER stress, and related apoptosis, making them alluring desirable therapeutic targets in PCOS-associated cardiac complications.

Establishment of an inflammation-related acute lung injury/acute respiratory distress syndrome rat model supported by venovenous extracorporeal membrane oxygenation.

The major concerns for patients who have acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 or sepsis and undergone successful venovenous extracorporeal membrane oxygenation (VV ECMO) include a low survival rate and an uncontrollable inflammatory response. This study aimed to introduce an inflammation-related ALI/ARDS rat model supported by VV ECMO that is more suitable for clinical application to assess the immune response and thereby further improve survival after VV ECMO. Rats were randomly divided into three groups: the sham group, the lipopolysaccharide (LPS) group, and the LPS + ECMO group. ALI/ARDS was induced via intratracheal instillation of LPS in rats. A 5.5 F specially designed bicaval cannulation was placed in the external jugular vein for drainage and reflux. Femoral artery cannulation was used to monitor blood pressure during surgery. Arterial blood gas was measured at baseline and 3 h after VV ECMO support. Finally, lung tissue, bronchoalveolar lavage fluid (BALF) and blood samples were harvested for further evaluation. All LPS-induced ALI/ARDS rats were successfully supported by VV ECMO. The rats survived during the supporting process and maintained effective blood pressure and electrocardiogram (ECG) activity. Compared with the LPS group, VV ECMO support provided oxygen supply to restore lung function and reduced lung injury. We successfully established an inflammation-related ALI/ARDS rat model supported by VV ECMO, in which VV ECMO support alleviated lung injury. Our rat model provides a new tool for immunological research on inflammation-related ALI/ARDS during VV ECMO.

Metformin activates SIRT2 to improve insulin resistance and promote granulosa cell glycolysis in a rat model of polycystic ovary syndrome.

Metformin activates SIRT2 to improve insulin resistance and promote granulosa cell glycolysis in a rat model of polycystic ovary syndrome.