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阿魏酸对链脲佐菌素诱导的糖尿病大鼠肾病的保护作用。

Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats.

机构信息

Institution of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.

出版信息

Food Funct. 2020 Apr 1;11(4):3706-3718. doi: 10.1039/c9fo02398d. Epub 2020 Apr 20.

Abstract

Diabetic nephropathy (DN) is a major and severe complication of diabetes mellitus. Ferulic acid (FA), a phenolic compound widespread in fruits and plants, displays a variety of pharmacological activities including regulating blood glucose and lipids, anti-oxidation, anti-inflammation and anti-fibrosis. The study was aimed to investigate the renal protective effects of FA on diabetic rats and elucidate the underlying mechanisms. FA (100 mg kg, i.g., once a day) was administered to DN rats for 8 weeks. The organ coefficient of kidneys was calculated. Levels of UP, BUN, Cr, FBG, TC and TG in serum were measured. Activities of SOD, CAT and GPx and the content of MDA in renal tissues were assayed. Pathological changes in renal tissues were observed by HE staining, PAS staining, PASM staining, Masson staining and transmission electron microscopy. p-NF-κB p65, TNF-α, TGF-β1, collagen IV, nephrin and podocin protein expressed in renal tissues were determined by immunohistochemistry and western blotting. Results showed that FA significantly improved the kidney organ coefficient, decreased the UP, BUN, Cr, FBG, TC and TG levels in serum, increased SOD, CAT and GPx activities, reduced MDA content in renal tissues and alleviated pathological injury of the renal tissues. What's more, long-term treatment with FA considerably down-regulated the expressions of p-NF-κB p65, TNF-α, TGF-β1 and collagen IV proteins, and up-regulated the expressions of nephrin and podocin proteins in renal tissues. FA could be a renoprotective agent by attenuating oxidative stress, inflammation, and fibrosis, as well as improving podocyte injury in STZ-induced DN rats.

摘要

糖尿病肾病(DN)是糖尿病的一种主要且严重的并发症。阿魏酸(FA)是一种广泛存在于水果和植物中的酚类化合物,具有多种药理活性,包括调节血糖和血脂、抗氧化、抗炎和抗纤维化。本研究旨在探讨 FA 对糖尿病大鼠的肾脏保护作用,并阐明其潜在机制。FA(100mg/kg,ig,每天一次)给予 DN 大鼠 8 周。计算肾脏器官系数。测定血清中 UP、BUN、Cr、FBG、TC 和 TG 水平。测定肾组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的活性以及丙二醛(MDA)的含量。通过 HE 染色、PAS 染色、PASM 染色、Masson 染色和透射电镜观察肾组织的病理变化。通过免疫组化和 Western blot 测定肾组织中 p-NF-κB p65、TNF-α、TGF-β1、胶原 IV、nephrin 和 podocin 蛋白的表达。结果表明,FA 显著改善了肾脏器官系数,降低了血清中 UP、BUN、Cr、FBG、TC 和 TG 水平,提高了 SOD、CAT 和 GPx 的活性,降低了肾组织中 MDA 的含量,减轻了肾组织的病理损伤。此外,长期给予 FA 可显著下调 p-NF-κB p65、TNF-α、TGF-β1 和胶原 IV 蛋白的表达,上调肾组织中 nephrin 和 podocin 蛋白的表达。FA 可能通过减轻氧化应激、炎症和纤维化以及改善 STZ 诱导的 DN 大鼠足细胞损伤来发挥肾脏保护作用。

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