Pitavastatin Exhibits Protective Effects on Podocytes Accompanied by BMP-7 Up-Regulation and Rho Suppression
Pitavastatin Exhibits Protective Effects on Podocytes Accompanied by BMP-7 Up-Regulation and Rho Suppression
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DOI：
10.1159/000444397
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发表时间：
2016-02
期刊：
影响因子：
3.1
通讯作者：
Makoto Ohigashi;Nobuyoshi Imai;H. Toba;M. Kobara;T. Nakata
中科院分区：
文献类型：
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作者：
Makoto Ohigashi;Nobuyoshi Imai;H. Toba;M. Kobara;T. Nakata
背景/目的：足细胞损伤参与糖尿病肾病的发生发展。本研究旨在证实匹伐他汀对糖尿病大鼠肾脏和足细胞的保护作用，并阐明其作用机制。方法：将Wistar大鼠随机分为4组：对照组、链脲佐菌素(STZ；55 mg/kg)诱导的糖尿病组、STZ+匹拉伐他汀(10 mg/kg/d)组、STZ+丹参酚(1 mm o l/L)组。结果：链脲佐菌素诱导的糖尿病大鼠尿蛋白排泄量增加，血肌酐升高，内生肌酐清除率降低。匹伐他汀在不降低胆固醇水平的情况下显著改善了这些参数，而坦泊尔则没有。链脲佐菌素可促进肾间质纤维化、系膜细胞增殖、转化生长因子-β、单核细胞趋化蛋白-1的表达，抑制Rho蛋白的表达，同时减少肾皮质骨形态发生蛋白-7的表达。此外，STZ还降低了足细胞相关因子、足细胞中的podocin和neparin以及BMP-7。匹伐他汀可显著改善上述指标。而坦普尔仅对转化生长因子-β、单核细胞趋化蛋白-1和组织学改变有改善作用。结论：匹伐他汀具有肾脏和足细胞保护作用，并伴有BMP-7的保护和Rho的抑制。
Background/Aims: Podocytes injury is involved in the development of diabetic nephropathy. This study was designed to confirm the reno- and podocyte-protective effects of pitavastatin in diabetic rats and clarify its mechanisms. Methods: Wistar rats were divided into 4 treatment groups: control, streptozotocin (STZ; 55 mg/kg)-induced diabetes, STZ with pitavastatin (10 mg/kg/day), and STZ with tempol (1 mmol/l). Results: STZ-induced diabetic rats exhibited increases in urinary protein excretion and plasma creatinine, and a decrease in creatinine clearance. Pitavastatin significantly improved these parameters without reducing cholesterol levels, whereas tempol did not. The treatment with STZ-enhanced renal fibrosis, mesangial proliferation, transforming growth factor (TGF)-β, MCP-1 and suppressed Rho in association with decrement of bone morphogenetic protein (BMP)-7 expression in renal cortex. Moreover, STZ decreased podocyte related factors, podocin and nephrin, and BMP-7 in podocytes. Pitavastatin significantly ameliorated all these indices. On the other hand, improvement by tempol was found only in TGF-β, MCP-1 and histological changes. Conclusion: Pitavastatin exhibited reno- and podocyte-protective effects accompanied by BMP-7 preservation and Rho suppression.