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紫杉醇通过下调 TGF-β1/Smad 通路改善糖尿病肾病。

Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF-β1/Smad pathway.

机构信息

Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.

Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.

出版信息

Chin J Nat Med. 2018 Feb;16(2):90-96. doi: 10.1016/S1875-5364(18)30034-7.

Abstract

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.

摘要

糖尿病肾病(DN)是糖尿病常见的微血管并发症之一。肾纤维化与肾功能恶化密切相关。本研究旨在探讨紫杉醇对高脂饮食/链脲佐菌素诱导的大鼠糖尿病肾病的保护作用及其作用机制。通过 4 周高脂饮食喂养和随后腹腔注射链脲佐菌素(30mg·kg 体重)建立大鼠糖尿病肾病模型。选择血糖水平高于 16.8mmol·L 的大鼠进行实验。DN 大鼠每天口服紫杉醇(0.32、0.64 和 1.28g·kg)一次,持续 8 周。紫杉醇显著改善了肾脏损伤,表现为 24 小时尿白蛋白排泄率、血清肌酐和血尿素氮降低。组织病理学检查证实了紫杉醇的保护作用。肾小球基底膜厚度降低,系膜细胞和足细胞增殖以及系膜基质增加得到抑制。进一步的实验表明,紫杉醇处理下调了 TGF-β1 和 α-SMA 的表达,抑制了 Smad2 和 Smad3 的磷酸化。这些结果表明,紫杉醇减轻了糖尿病肾病大鼠的肾脏损伤,这可能与抑制 TGF-β1/Smad 信号通路有关。

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