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京尼平抑制线粒体解偶联蛋白 2 的表达并改善糖尿病小鼠的足细胞损伤。

Genipin inhibits mitochondrial uncoupling protein 2 expression and ameliorates podocyte injury in diabetic mice.

机构信息

Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

PLoS One. 2012;7(7):e41391. doi: 10.1371/journal.pone.0041391. Epub 2012 Jul 19.

DOI:10.1371/journal.pone.0041391
PMID:22848482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3405128/
Abstract

Diabetic nephropathy (DN) is one of the most common causes of end stage renal disease (ESRD) in China, which requires renal replacement therapy. Recent investigations have suggested an essential role of podocyte injury in the initial stage of DN. This study investigated the potential therapeutic role of genipin, an active extract from a traditional Chinese medicine, on progression of DN in diabetic mice induced by intraperitoneally injection of streptozocin (STZ). In diabetic mice, orally administration of genipin postponed the progression of DN, as demonstrated by ameliorating body weight loss and urine albumin leakage, attenuating glomerular basement membrane thickness, restoring the podocyte expression of podocin and WT1 in diabetic mice. The protective role of genipin on DN is probably through suppressing the up-regulation of mitochondrial uncoupling protein 2 (UCP2) in diabetic kidneys. Meanwhile, through inhibiting the up-regulation of UCP2, genipin restores podocin and WT1 expression in cultured podocytes and attenuates glucose-induced albumin leakage through podocytes monolayer. Therefore, these results revealed that genipin inhibited UCP2 expression and ameliorated podocyte injury in DN mice.

摘要

糖尿病肾病 (DN) 是中国终末期肾病 (ESRD) 最常见的原因之一，需要肾脏替代治疗。最近的研究表明，足细胞损伤在 DN 的初始阶段起着重要作用。本研究探讨了京尼平，一种中药有效提取物，对链脲佐菌素 (STZ) 腹腔注射诱导的糖尿病小鼠 DN 进展的潜在治疗作用。在糖尿病小鼠中，京尼平的口服给药延缓了 DN 的进展，表现为改善体重减轻和尿白蛋白漏出，减轻肾小球基底膜厚度，恢复糖尿病小鼠足细胞中 podocin 和 WT1 的表达。京尼平对 DN 的保护作用可能是通过抑制糖尿病肾脏中线粒体解偶联蛋白 2 (UCP2) 的上调。同时，京尼平通过抑制 UCP2 的上调，恢复了培养足细胞中 podocin 和 WT1 的表达，并通过足细胞单层减轻葡萄糖诱导的白蛋白漏出。因此，这些结果表明，京尼平抑制了 UCP2 的表达，改善了糖尿病小鼠的足细胞损伤。

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