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首页> 外文期刊>Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association >Selective phosphodiesterase-5 (PDE-5) inhibitor vardenafil ameliorates renal damage in type 1 diabetic rats by restoring cyclic 3',5' guanosine monophosphate (cGMP) level in podocytes.
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Selective phosphodiesterase-5 (PDE-5) inhibitor vardenafil ameliorates renal damage in type 1 diabetic rats by restoring cyclic 3',5' guanosine monophosphate (cGMP) level in podocytes.

机译:选择性磷酸二酯酶5(PDE-5)抑制剂伐地那非可通过恢复足细胞中的环状3',5'鸟苷单磷酸(cGMP)水平来改善1型糖尿病大鼠的肾脏损害。

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摘要

Diabetic nephropathy (DN) is characterized by podocyte damage and increased phosphodiesterase-5 (PDE-5) activity-exacerbating nitric oxide (NO)-cyclic 3',5' guanosine monophosphate (cGMP) pathway dysfunction. It has been shown that PDE-5 inhibition ameliorates DN. The role of podocytes in this mechanism remains unclear. We investigated how selective PDE-5 inhibition influences podocyte damage in streptozotocin (STZ) diabetic rats.Male Sprague-Dawley rats (250-300 g) were injected with STZ and divided into two groups: (i) STZ control (non-treated, STZ, n=6) and (ii) STZ+vardenafil treatment (10 mg/kg/day, STZ-Vard, n=8). Non-diabetic rats served as negative controls (Control, n=7). Following 8 weeks of treatment, immunohistochemical and molecular analysis of the kidneys were performed.Diabetic rats had proteinuria, increased renal transforming growth factor (TGF)-β1 expression and podocyte damage when compared with controls. Vardenafil treatment resulted in preserved podocyte cGMP levels, less proteinuria, reduced renal TGF-β1 expression, desmin immunostaining in podocytes and restored both nephrin and podocin mRNA expression. Diabetes led to increased glomerular nitrotyrosine formation and renal neuronal nitric oxide synthase and endothelial nitric oxide synthase mRNA expression, but vardenafil did not influence these parameters.Our data suggest that a dysfunctional NO-cGMP pathway exacerbates podocyte damage in diabetes. In conclusion, vardenafil treatment preserves podocyte function and reduces glomerular damage, which indicates therapeutic potential in patients with DN.
机译:糖尿病肾病(DN)的特征是足细胞损伤和磷酸二酯酶5(PDE-5)活性增强,加剧一氧化氮(NO)-环3',5'鸟苷单磷酸(cGMP)途径功能障碍。已经显示,PDE-5抑制可改善DN。足细胞在这种机制中的作用尚不清楚。我们研究了选择性PDE-5抑制作用如何影响链脲佐菌素(STZ)糖尿病大鼠的足细胞损伤。向雄性Sprague-Dawley大鼠(250-300 g)注射STZ并分为两组:(i)STZ对照(未经治疗, STZ,n = 6)和(ii)STZ + vardenafil治疗(10 mg / kg /天,STZ-Vard,n = 8)。非糖尿病大鼠用作阴性对照(对照,n = 7)。治疗8周后,对肾脏进行免疫组织化学和分子分析。与对照组相比,糖尿病大鼠具有蛋白尿,肾转化生长因子(TGF)-β1表达增加和足细胞损伤。伐地那非治疗可导致足细胞cGMP含量保持不变,蛋白尿减少,肾脏TGF-β1表达降低,足细胞中结蛋白免疫染色并恢复了肾素和Podocin mRNA的表达。糖尿病导致肾小球硝基酪氨酸形成增加,肾神经元一氧化氮合酶和内皮型一氧化氮合酶mRNA表达增加,但伐地那非并未影响这些参数。我们的数据表明,功能异常的NO-cGMP途径加剧了糖尿病足细胞的损害。总之,伐地那非治疗可保留足细胞功能并减少肾小球损害,这表明对DN患者具有治疗潜力。

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