糖尿病肾病足细胞损伤病理机制及中药干预作用.doc

糖尿病肾病足细胞损伤病理机制及中药干预作用 　　[摘要] 在糖尿病肾病（diabetic nephropathy，DN）进程中，足细胞损伤与蛋白尿密切相关。足细胞损伤的病理特征主要是指足细胞形态和功能的改变，包括足突融合、足细胞数量和密度减少、足细胞凋亡、足细胞上皮-间充质转分化以及足细胞肥大等。这些病理性损伤受控于肾组织内多条信号调控途径，如哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）/自噬通路、转化生长因子（transforming growth factor，TGF）-β1通路以及Notch通路等。以雷公藤制剂为代表的一些中药提取物，如雷公藤多苷（multiglycoside of Tripterygium wilfordii，GTW）、雷公藤甲素（triptolide，TP）、黄芪多糖（astragalus polysaccharide，APS）、黄芪甲苷（astragaloside IV，AS-IV）以及三七总皂苷（Panax notoginseng saponins，PNS）在体内外对DN模型鼠足细胞病变或高糖诱导的足细胞损伤都具有一定的保护作用。国内的初步研究表明，GTW很可能通过调控DN模型鼠肾组织mTORC1信号通路活性而改善足细胞损伤。因此，基于DN足细胞损伤的信号调控途径而探讨中药干预作用的研究是今后的发展方向。 　　[关键词] 糖尿病肾病；中药；足细胞；病理机制；mTOR/自噬信号通路 　　[Abstract] Podocyte injury is closely related to proteinuria in the progress of diabetic nephropathy（DN）. The pathological characters of podocyte injury mainly refer to the change of podocyte form and function， including foot process effacement， reduction of podocyte number and density， podocyte apoptosis， podocyte epithelial-mesenchymal transdifferentiation（EMT）and podocyte hypertrophy. These pathological damages are controlled by multiple signaling pathways in the kidney， such as mammalian target of rapamycin（mTOR）/autophagy pathway， transforming growth factor（TGF）-β1 pathway and Notch pathway. For podocyte injuries induced by high glucose or in murine models of DN， some Chinese herbal medicine（CHM）extracts， such as multiglycoside of Tripterygium wilfordii（GTW）， triptolide（TP）， astragaloside IV（AS-IV）， astragalus polysaccharide（APS）and Panax notoginseng saponins（PNS）， have the protective effects in vivo or in vitro. The preliminary studies in China showed that GTW improves podocyte injury in the DN model rats probably through regulating the activity of mTORC1 signaling pathway in the kidney. Therefore， it is the developmental direction for the further study to clarify the interventional effects of CHM based on podocyte injury-related signaling pathway in DN. 　　[Key words] diabetic nephropathy；Chinese herbal medicine；podocyte；path