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 ◽  
...  

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.

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Yunqiang He ◽  
Ziqiang Xu ◽  
Mingshi Zhou ◽  
Minmin Wu ◽  
Xuehai Chen ◽  
...  

Objective. Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus, and insulin therapy has many side effects in the treatment of DN. Islet transplantation has emerged as a promising therapy for diabetic patients. This study was established to investigate its advantageous effects in a rat model of early DN.Methods. Streptozotocin was administered to the rats to induce diabetes. Twelve weeks later, the diabetic rats were divided into 3 groups: the islet-transplanted group (IT group), the insulin-treated group (IN group), and the untreated group (DN group). Renal injury and kidney structure were assessed by urinalysis and transmission electron microscopy (TEM) detection. Immunohistochemical staining and western blotting were performed to assess renal fibrosis levels.Results. The early DN features were reversed and the glomerular filtration barrier and basement membrane structures were improved at 4 weeks after islet transplantation. The urine microalbumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, and mean thickness of the glomerular basement membrane (GBM) were significantly decreased in the IT group. The expression of renal fibrotic factors was also significantly decreased.Conclusions. These data suggest that early DN can be reversed after islet transplantation, and they may facilitate the development of a clinical therapeutic strategy for human diabetes mellitus.


Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 740-747
Author(s):  
Jiangning Yin ◽  
Jun Jiang ◽  
Huajun Wang ◽  
Guoyuan Lu

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.


2020 ◽  
Vol 319 (4) ◽  
pp. F697-F711 ◽  
Author(s):  
Guang Liu ◽  
Courtney M. Shea ◽  
Juli E. Jones ◽  
Gavrielle M. Price ◽  
William Warren ◽  
...  

Praliciguat, a clinical-stage soluble guanylate cyclase (sGC) stimulator, increases cGMP via the nitric oxide-sGC pathway. Praliciguat has been shown to be renoprotective in rodent models of hypertensive nephropathy and renal fibrosis. In the present study, praliciguat alone and in combination with enalapril attenuated proteinuria in the obese ZSF1 rat model of diabetic nephropathy. Praliciguat monotherapy did not affect hemodynamics. In contrast, enalapril monotherapy lowered blood pressure but did not attenuate proteinuria. Renal expression of genes in pathways involved in inflammation, fibrosis, oxidative stress, and kidney injury was lower in praliciguat-treated obese ZSF1 rats than in obese control rats; fasting glucose and cholesterol were also lower with praliciguat treatment. To gain insight into how tubular mechanisms might contribute to its pharmacological effects on the kidneys, we studied the effects of praliciguat on pathological processes and signaling pathways in cultured human primary renal proximal tubular epithelial cells (RPTCs). Praliciguat inhibited the expression of proinflammatory cytokines and secretion of monocyte chemoattractant protein-1 in tumor necrosis factor-α-challenged RPTCs. Praliciguat treatment also attenuated transforming growth factor-β-mediated apoptosis, changes to a mesenchyme-like cellular phenotype, and phosphorylation of SMAD3 in RPTCs. In conclusion, praliciguat improved proteinuria in the ZSF1 rat model of diabetic nephropathy, and its actions in human RPTCs suggest that tubular effects may contribute to its renal benefits, building upon strong evidence for the role of cGMP signaling in renal health.


2016 ◽  
Vol 57 (3) ◽  
pp. 664 ◽  
Author(s):  
Bo Hwan Kim ◽  
Eun Soo Lee ◽  
Ran Choi ◽  
Jarinyaporn Nawaboot ◽  
Mi Young Lee ◽  
...  

Renal Failure ◽  
2015 ◽  
Vol 38 (1) ◽  
pp. 124-130 ◽  
Author(s):  
Qing Zhang ◽  
Yongqiang Ji ◽  
Wei Lv ◽  
Tianwei He ◽  
Jianping Wang

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jang Hyun Koh ◽  
Eun Soo Lee ◽  
Miri Hyun ◽  
Hong Min Kim ◽  
Yoon Jung Choi ◽  
...  

The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10), OLETF rats as diabetic control group (n=10), and OLETF rats treated with taurine group (n=10). We treated taurine (200 mg/kg/day) for 20 weeks and treated high glucose (HG, 30 mM) with or without taurine (30 mM) in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS) levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.


2018 ◽  
Vol 2018 ◽  
pp. 1-13
Author(s):  
Jun Jiang ◽  
Jiangning Yin ◽  
Xiang Liu ◽  
Huajun Wang ◽  
Guoyuan Lu

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.


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