mTOR信号通路调控糖尿病肾病肾小球肥大的机制及中药的干预作用  

Regulative mechanisms of mammalian target of rapamycin signaling pathway in glomerular hypertrophy in diabetic nephropathy and interventional effects of Chinese herbal medicine

作　　者：杨晶晶[1] 黄燕如 万毅刚[3] 沈山梅[4] 毛志敏[1] 吴薇[1] 姚建 

机构地区：[1]南京中医药大学中西医结合鼓楼临床医学院,江苏南京210029 [2]Department of Molecular,Signaling University of Yamanashi [3]南京大学医学院附属鼓楼医院中医科,江苏南京210008 [4]南京大学医学院附属鼓楼医院内分泌科,江苏南京210008

出　　处：《中国中药杂志》2015年第16期3125-3131,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81374030);南京市卫生青年人才培养工程项目

摘　　要：肾小球肥大(glomerular hypertrophy)是糖尿病肾病(diabetic nephropathy,DN)早期阶段最主要的病理特征,其调控机制与哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)信号通路活性密切相关。m TOR包括m TORC1和m TORC2,其中,m TORC1上游信号通路是磷脂酰肌醇3激酶(phosphatidylinositol-3-kinase,PI3K)/丝氨酸-苏氨酸激酶(serinethreonine kinase,Akt)/5-单磷酸腺苷活性蛋白激酶(adenosine monophosphate activated protein kinase,AMPK),其代表性的下游信号分子是4E结合蛋白(4E-binding proteins,4EBP)和70 k D核糖体S6激酶(phosphoprotein 70 S6Kinase,p70S6K)。一些中药提取物可以在体外通过干预PI3K/Akt/m TOR信号通路关键上、下游信号分子的表达而改善细胞增殖。对于肾小球系膜细胞和足细胞,m TOR通过调节细胞周期、能量代谢以及相关的基质蛋白合成等多种途径对肾小球固有细胞发挥着重要的调控作用。对于DN动物模型,m TOR抑制剂——雷帕霉素可抑制肾小球固有细胞肥大、增殖以及相应的肾小球基底膜增厚和系膜基质沉积。一些中药提取物在体内外可以通过干预DN肾组织或肾脏固有细胞m TOR信号通路的活性而减轻相应的肾小球病变。Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy（DN） , and its regulatory mechanism is closely related to mammalian target of rapamycin（mTOR） signaling pathway activity, mTOR includes mTORcomplex 1 （ mTORC1 ） and mTOR complex 2 （ mTORC2）, in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase （PI3K）/serine-threonine kinase（Akt）/adenosine monophosphate activated protein kinase（AMPK）, and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins （4EBP）and phosphoprotein 70 S6Kinase （p70S6K）. Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or down- stream of PI3K/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells（MC） and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamy- cin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane （GBM） thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular le- sions by intervening roTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.

关 键 词：糖尿病肾病 中药 肾小球肥大 MTOR信号通路 

分 类 号：R285[医药卫生—中药学]