scholarly journals Erzhi Formula Extracts Reverse Renal Injury in Diabetic Nephropathy Rats by Protecting the Renal Podocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-13
Author(s):  
Jun Jiang ◽  
Jiangning Yin ◽  
Xiang Liu ◽  
Huajun Wang ◽  
Guoyuan Lu
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Renal Tubule ◽  
Rat Kidney ◽  
Inflammatory Factors ◽  
Model Group ◽  
Urine Protein ◽  
Sod Activity ◽  
Pas Staining ◽  
Glomerular Morphology

Podocytes injury was a crucial factor resulting in diabetic nephropathy (DN). Erzhi formula extract (EZF) was a clinical effective Chinese medicine on DN, but its mechanism was unclear. In this study, the main compounds of EZF and their pharmacokinetics in rat were detected by HPLC-MS/MS. And then, blood glucose, urine protein, renal index, renal microstructural (HE/PAS staining), inflammatory factors (IL-β, TNF-α, IL-6), and protein/mRNA expression related to the function of podocyte (CD2AP and Podocin) in DN rats were investigated after the oral administration of EZF. The concentrations of specnuezhenide and wedelolactone in rat kidney were 7.19 and 0.057 mg/kg, respectively. The Tmax of specnuezhenide and wedelolactone were 2.0 and 1.50 h, respectively. Their Cmax were, respectively, 30.24 ± 2.68 and 6.39 ± 0.05 μg/L. Their AUC(0-∞) were 123.30 ± 2.68 and 16.56 ± 0.98 μg/L⁎h, respectively. Compared with the model group, the blood glucose and the 24-hour urinary protein were significantly decreased (P < 0.05) after 16 weeks’ treatment of EZF. The expressions of Podocin and CD2AP protein/mRNA were increased (P < 0. 05). The deteriorate of glomerular morphology was alleviated under the treatment of EZF. EZF prominently decreased the levels of inflammatory factors (P < 0.05). MDA was significantly decreased (P < 0.05) with the significant increase of SOD activity (P < 0.05) in EZF groups. All the results proved that EZF repaired glomerular mesangial matrix, protected renal tubule, and improved renal function in DN rats by upregulating the expression of Podocin and CD2AP protein/mRNA in podocytes.

scholarly journals Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 890-898 ◽  
Author(s):  
Chen Jihua ◽  
Chen Cai ◽  
Bao Xubin ◽  
Yu Yue
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Rat Kidney ◽  
Diabetic Rats ◽  
Immunohistochemical Method ◽  
Model Group ◽  
Protein Expressions ◽  
Masson Staining

AbstractObjectiveTo investigate the effects and mechanisms of dexmedetomidine (Dex) on model rats of diabetic nephropathy (DN).MethodsRats were divided into NC, model, Dex-L (1μg/ kg), Dex-M (5μg/kg) and Dex-H (10μg/kg) groups. Rats in all groups except in the NC group were injected with streptozotocin (STZ) combined with right nephrectomy. Rats in Dex (1, 5 and 10μg/kg) groups received gavage with Dex (1, 5 and 10μg/kg). After 4 weeks, rats were sacrificed and kidneys were collected. HE staining was performed for a renal injury. Masson staining was applied to detect the fibrotic accumulation in rat kidney. Radioimmunoassay was used to test the renal function. Immunohistochemical method was used to detect protein expressions of RhoA, p-MYPT and Nox4 in rat kidney.ResultsCompared with the NC group, the levels of urine microalbumin in protein, α1-MG and β2-MG, renal fibrotic accumulation, RhoA, p-MYPT, Nox4 and α-SMA in model group increased significantly (P＜0.001, respectively). Compared with the model group, Dex low, medium and high groups improved the deposition of renal fiber in rats, inhibited the expression levels of microalbumin, α1-MG and β2-MG in urine and decreased expression of RhoA, p-MYPT, Nox4 and α-SMA proteins (P＜0.05, P＜0.01).ConclusionDex is possible to inhibit the expression of α-SMA and renal fibrous substance deposition in rat kidney via RhoA/ROCK/Nox4 signaling pathway, thereby reducing early kidney damage in model rats.

scholarly journals Berberine Reduces Renal Cell Pyroptosis in Golden Hamsters with Diabetic Nephropathy through the Nrf2-NLRP3-Caspase-1-GSDMD Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Baozhu Ding ◽  
Songyan Geng ◽  
Xiaojie Hou ◽  
Xuelian Ma ◽  
Huazhou Xu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Blood Lipids ◽  
Kidney Tissue ◽  
Inflammatory Factors ◽  
Control Group ◽  
Model Group ◽  
Golden Hamsters ◽  
Caspase 1 ◽  
Tnf Α ◽  
Nrf2 Expression

Objective. To observe the effect of berberine (BBR) on kidney cell pyroptosis in golden hamsters with diabetic nephropathy (DN) and to explore the molecular mechanism of its renal protection. Methods. Fifty clean-grade male golden hamsters were randomly divided into a control group (10) and a model building group (40). The DN model was established by high-sugar and high-fat feeding and injection of a small amount of STZ. After successful establishment of the model, they were randomly divided into a model group, western medicine group, and berberine high- and low-dose groups. The western medicine group was given irbesartan 13.5 mg/kg, and the berberine high- and low-dose groups were given BBR 200 mg/kg and 100 mg/kg, respectively, for 8 consecutive weeks. An automatic biochemical analyser was used to measure blood glucose, blood lipids, kidney function, MDA, and other indicators; radioimmunoassay was used to assess serum insulin; enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1β, IL-6, IL-18, TNF-α; HE, PAS, and Masson staining were used to observe kidney pathological tissue morphology; western blot and real-time fluorescent quantitative PCR were used to assess protein and mRNA expression of molecules, such as Nrf2, NLRP3, Caspase-1, and GSDMD; and TUNEL staining was used to detect DNA damage. SPSS statistical software was used for the data analysis. Results. The kidney tissues of golden hamsters in the control group were normal; Nrf2 was highly expressed, serum MDA level was low, NLRP3 expression in kidney tissue was not obvious, Caspase-1 and GSDMD were weakly expressed, and only a few TUNEL-positive cells were observed. Compared with the control group, the golden hamsters in the model group had obvious renal pathological damage; blood glucose, blood lipids, renal function-related indexes, insulin, and inflammatory factors IL-1β, IL-6, IL-18, and TNF-α were increased ( P < 0.05 ); NLRP3, Caspase-1, and GSDMD expression was increased; Nrf2 expression was decreased; MDA level was increased ( P < 0.05 ); and the number of TUNEL-positive cells was increased. Compared with the model group, the pathological morphology of the kidney tissue of golden hamsters in the three treatment groups was significantly improved; blood glucose, blood lipids, renal function, and the expression of inflammatory factors IL-1β and IL-6 were reduced ( P < 0.05 ); NLRP3, Caspase-1, GSDMD, and other molecular proteins and mRNA expression were decreased; Nrf2 expression was increased; MDA level was decreased ( P < 0.05 ); and the number of TUNEL-positive cells was decreased. Conclusion. DN golden hamster kidney NLRP3-Caspase-1-GSDMD signalling was enhanced. BBR can reduce oxidative stress damage by regulating antioxidative Nrf2 and then regulating NLRP3-Caspase-1-GSDMD signalling to inhibit pyroptosis, antagonizing DN inflammation-induced damage.

scholarly journals Psoriasis-Like Inflammation Induced Renal Dysfunction through the TLR/NF-κB Signal Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Fang Ren ◽  
Min Zhang ◽  
Caiyun Zhang ◽  
Hong Sang
Keyword(s):  
Renal Injury ◽  
Periodic Acid ◽  
Severity Index ◽  
Skin Lesions ◽  
Signal Pathway ◽  
Inflammatory Factors ◽  
Urine Protein ◽  
Periodic Acid Schiff ◽  
Associated Proteins ◽  
Pas Staining

Pathological studies have shown an association between psoriasis and renal injury (RI), but the mechanism between RI and psoriasis was still unclear. This paper was designed to investigate the relationship and mechanism between psoriasis-like inflammation and renal injury in BALB/C mice. Mice were topically smeared imiquimod followed by various analyses in skin lesions, urine protein, kidney/serum inflammatory cytokines, kidney function, podocyte membrane proteins, and toll-like receptors/nuclear factor kappa-b (TLR/NF-κB) pathway-associated proteins. Meanwhile, lipopolysaccharide (LPS) and dexamethasone (DEX) were intraperitoneally injected to promote and inhibit inflammation accompanied by imiquimod to elaborate the relevance between inflammatory levels and RI. In the model group, the Psoriasis Area and Severity Index (PASI) scores of scaly and erythema obviously increased (p<0.01), creatinine and blood urea nitrogen significantly increased (p<0.01), the positive area of hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining in kidney increased (p<0.01), malondialdehyde significantly increased with superoxide dismutase (SOD) decreased (p<0.01), 24-hour urine protein increased and the expressions of podocin and CD2 associate protein (CD2AP) decreased (p<0.01), and kidney/serum inflammatory factors (IL-17, IL-1β, IL-6, TNF-α, and IL-22) and TLR/NF-κB-related expression (TLR2, TLR4, MyD88, and NF-κBp65) all increased (p<0.01). The RI was aggravated with the TLR/NF-κB related expression being upregulated by LPS (p<0.05). On the contrary, the RI was alleviated by DEX (p<0.05). Our data showed that psoriasis-like inflammation damaged the renal function via the TLR/NF-κB signal pathway. Inhibiting TLR/NF-κB-related protein expression may be effective for the treatment of RI caused by psoriasis.

scholarly journals Protective effects of specneuzhenide on renal injury in rats with diabetic nephropathy

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 740-747
Author(s):  
Jiangning Yin ◽  
Jun Jiang ◽  
Huajun Wang ◽  
Guoyuan Lu
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Low Dose ◽  
High Dose ◽  
Protective Effects ◽  
Model Group ◽  
Urine Protein ◽  
Tnf Α ◽  
Glomerular Lesions

AbstractBackgroundWe aim to investigate the protective effects and potential mechanisms in specneuzhenide (SPE) on renal injury in rats with diabetic nephropathy (DN).ResultsSPE could inhibit the decrease of body weight compared with the model group (P<0.05), and trigger improvement in the renal index (P<0.05). High dose and low dose SPE could trigger a significant decrease in serum IL1β, IL-6 and TNF-α compared with the model group (P<0.05). SPE could attenuate the glomerular lesions in DN rats. SPE induced up-regulation of podocin and CD2AP (P<0.05).ConclusionSPE showed protective effects on renal injury through attenuating the pathological injury and urine protein. This process may be closely related to the modulation of CD2AP and podocin expression.

scholarly journals Combined Microencapsulated Islet Transplantation and Revascularization of Aortorenal Bypass in a Diabetic Nephropathy Rat Model

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yunqiang He ◽  
Ziqiang Xu ◽  
Hongxing Fu ◽  
Bin Chen ◽  
Silu Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Islet Transplantation ◽  
Rat Model ◽  
Good Control ◽  
Protective Effects ◽  
Urine Protein ◽  
Monocyte Chemoattractant Protein 1 ◽  
Filtration Barrier ◽  
Combined Strategy

Objective.Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS) in diabetic nephropathy (DN) patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model.Methods.A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group. The levels of blood glucose and urine protein were measured, and changes in renal pathology were observed. The expression of monocyte chemoattractant protein-1 (MCP-1) in graft vessels was assessed by immunohistochemical staining. Histopathological staining was performed to assess the pathological changes of glomeruli and tubules.Results.The levels of urine protein and the expression of MCP-1 in graft vessels were decreased after islet transplantation. The injury of glomerular basement membrane and podocytes was significantly ameliorated.Conclusions.The combined strategy of revascularization and microencapsulated islet transplantation had multiple protective effects on diabetic nephropathy, including preventing atherosclerosis in the graft vessels and alleviating injury to the glomerular filtration barrier. This combined strategy may be helpful for DN patients with RAS.

scholarly journals Protective Effects of Adiponectin Against Diabetic Renal Injury in a Mouse Model of Diabetes

2017 ◽  
Vol 43 (2) ◽  
pp. 870-878 ◽  
Author(s):  
Jiacai Hu ◽  
Junjun Dong ◽  
Zhijie Yang ◽  
Hao Wu ◽  
Na Yang
Keyword(s):  
Blood Glucose ◽  
Renal Injury ◽  
Fasting Blood Glucose ◽  
Kidney Cortex ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Model Group ◽  
Β Cells ◽  
Sod Activity

Background/Aims: Adiponectin (Apn) has shown anti-diabetic and anti-inflammatory potential. In the study, we studied and tested the protective effects of Apn against diabetic renal injury and the possible mechanism of these effects. Methods: After 1 week of adaptive feeding, 30 mice were randomly divided into 5 groups: the control group, the model group, the Apn (L) group, the Apn (M) group and the Apn (H) group. All mice were marked and weighed. Following 4 weeks of a pro-diabetic high-fat diet, the model group and Apn groups were injected intraperitoneally with a high dose of STZ (85 mg/kg), while the normal control group was injected with sodium citrate. Fasting blood glucose was measured daily, starting 3 days after STZ injection. After confirming the success of the diabetic model by measuring blood glucose of more than 16.7 nM for 3 successive days, we observed the animal models for an additional 4 weeks. After body weights were measured, urinary albumin, urinary protein, SOD activity and malondialdehyde (MDA) were measured by ELISA, BCA and biochemical assay respectively . Moreover, plasma insulin was assayed by radioimmunoassay, insulin expression in pancreatic β cells was assayed by immunohistochemistry and receptor for advanced glycation end products (RAGE) and corresponding PKC and PKA signaling in the kidney cortex were also assayed by Western blot and Real-time PCR. Results: The results showed that Apn can significantly reduce MDA and enhance SOD activity. Moreover, Apn promoted the synthesis and secretion of insulin by islet β-cells and reduced RAGE accumulation in the kidney, which was associated with down-regulated PKC expression and upregulated PKA expression. Conclusion: Apn has protective effects against hyperglycemia and can effectively enhance antioxidation, promote the secretion of insulin and reduce the accumulation of glycosylated products in T2DM mice; these effects were associated with inhibition of PKC and promotion of PKA signaling.

PENGARUH PEMBERIAN KOMBINASI EKSTRAK BUAH MENGKUDU (Morinda citrifolia L.) DAN KUNYIT (Curcuma longa) TERHADAP HISTOPATOLOGI GINJAL TIKUS WISTAR YANG DIINDUKSI ALLOXAN

2020 ◽  
Vol 5 (2) ◽  
pp. 319-327
Author(s):  
Pelastri Rahayu ◽  
◽  
Retno Hestiningsih ◽  
Martini Martini ◽  
Dwi Sutiningsih ◽  
...  
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Curcuma Longa ◽  
Morinda Citrifolia ◽  
Control Group ◽  
Type I ◽  
Turmeric Extract ◽  
Measurement Results ◽  
Diabetes Nephropathy

The prevalence of DM in Riskesdas in 2018 according to the Perkeni consensus in 2015 is higher than according to the Perkeni consensus in 2011, the prevalence was10.9%. The disease can develop into diabetes nephropathy, Increased prevalence of diabetic nephropathy directly proportional with an increase in diabetes prevalence. Diabetic nephropathy is a microvascular complication in diabetics that develops around 30% in patients with type I DM and about 40% in patients with type II DM. Turmeric extract has antioxidant and anti-inflammatory effects to prevent the bad development of diabetes nephropathy. This study looked at the effect of giving a combination of noni and turmeric extract on histopathology of alloxan-induced renal rats. A total of 25 mice were divided into 5 treatment groups, namely the PI group (250 mg / kgBB extract dose), PII group (500 mg / kgBB extract dose), PIII group (750 mg / kgBB extract dose), positive control group (glibenklamid) and negative control group (without extract and glibenklamid). The study used Post Test Only Group. The highest percentage decrease in blood glucose in the PI group was 56.11% and the lowest decrease in the PIII group was 24.12% with p = 0.012. The results of the study were not based on the number of extract doses. The measurement results of rat body weight and glomerular diameter were not affected by blood glucose level with p = 0.700 for body weight and p = 0.187 for glomerular measurement results.

Theaflavin Enriched Black Tea Extract Alleviates Diabetic Nephropathy by Suppressing Hyperglycaemia-Mediated Oxidative Stress and Inflammation in Streptozotocin-Induced Rats

2020 ◽  
Vol 10 ◽  
Author(s):  
Dhrubajyoti Sarkar ◽  
Sekhar Kumar Bose ◽  
Tania Chakraborty ◽  
Souvik Roy
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Blood Urea Nitrogen ◽  
Phenolic Content ◽  
Black Tea ◽  
Total Phenolic ◽  
Urea Nitrogen ◽  
Black Tea Extract ◽  
Tea Extract

Background: Diabetic nephropathy (DN), a microvascular complication of diabetes has been a significant health issue globally. However, theaflavin enriched black tea extract (BTE-TF) could restrain DN. Objective: The main objective of this exploration was to elucidate the effect of BTE-TF on DN, though the underlying mechanism remains unclear and requires further investigation. Method: The tea leaves were fermented to get black tea extract. Total phenolic content and HPLC were carried out to determine the phenolic content and theaflavin in the extract. Streptozotocin induced diabetic rats were treated with 100, 200, and 400 mg/kg/day BTE-TF extract for 12 weeks. Biochemical parameters like blood glucose, creatinine, blood urea nitrogen (BUN), triglyceride and antioxidant parameters of kidney tissue were measured. Histology, immunohistochemistry and TUNEL assay were performed to observe the effect of the extract with comparison to the standard drug (Metformin 200mg/kg/day). Result: Treated animals exhibited reduced blood glucose levels, blood urea nitrogen (BUN), creatinine, and serum triglycerides. Further, BTE-TF restored the histological alterations in the kidney. Chronic hyperglycaemia resulted in a significant increase in oxidative stress and pro-inflammatory cytokines of NF-kβ pathway. BTE-TF attenuated oxidative stress (p<0.01), inflammation (p<0.05) and apoptosis (p<0.05). Conclusion: This study suggests that BTE-TF exerts a protective role against diabetes-induced renal injury by ameliorating oxidative stress, inflammation, and apoptosis.

Sequoyitol ameliorates diabetic nephropathy in diabetic rats induced with a high-fat diet and a low dose of streptozotocin

2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Low Dose ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
High Fat

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.

scholarly journals Aerobic Exercise Inhibits CUMS-Depressed Mice Hippocampal Inflammatory Response via Activating Hippocampal miR-223/TLR4/MyD88-NF-κB Pathway

2020 ◽  
Vol 17 (8) ◽  
pp. 2676 ◽  
Author(s):  
Honglin Qu ◽  
Ruilian Liu ◽  
Jiaqin Chen ◽  
Lan Zheng ◽  
Rui Chen
Keyword(s):  
Inflammatory Response ◽  
Aerobic Exercise ◽  
Exercise Group ◽  
Inflammatory Factors ◽  
Control Group ◽  
Mild Stress ◽  
Hippocampal Function ◽  
Model Group ◽  
Mice Model ◽  
Protein Levels

Objective: To investigate the role of aerobic exercise in inhibiting chronic unpredictable mild stress (CUMS) depressed mice hippocampal inflammatory response and its potential mechanisms. Methods: Fifty-four male eight-week-old C57BL/6 mice were divided as control group (CG) (18 mice) and model group (36 mice). Model group mice were treated with 13 chronic stimulating factors for 28 days to set up the CUMS depression model. Neurobehavioral assessment was performed after modeling. The mice in the model group were randomly divided into the control model group (MG) and the aerobic exercise group (EG), with 18mice in each group. The EG group carried out the adaptive training of the running platform: 10 m/min, 0° slope, and increased by 10 minutes per day for 6 days. The formal training was carried for 8 weeks with 10 m/min speed, 0° slope, 60 min/d, 6 d/Week. After the training, a neurobehavioral assessment was performed, and hippocampus IL-1β and IL-10 protein levels were detected by ELISA. RT–PCR was used to detect the expression of miR-223 and TLR4, MyD88, and NF-κB in the hippocampus. Western blot was used to detect the expression of TLR4 and phosphorylated NF-κBp65 protein in the hippocampus. Results: The hippocampus function of CUMS depression model mice was impaired. The forced swimming and forced tail suspension time were significantly prolonged, and inflammatory factors IL-1β were significantly increased in the hippocampus. Aerobic exercise significantly improves CUMS-depressed mice hippocampal function, effectively reducing depressive behavior and IL-1β levels, and increasing IL-10 levels. Besides, aerobic exercise significantly upregulates the expression level of miR-223 and inhibits the high expression of TLR4, MyD88, and NF-κB. Conclusion: Aerobic exercise significantly increases the CUMS-depressed mice hippocampus expression of miR-223, and inhibits the downstream TLR4/MyD88-NF-κB signaling pathway and the hippocampal inflammatory response, which contributes to the improvement of the hippocampal function.

Sign in / Sign up

Export Citation Format

Share Document