α-硫辛酸通过激活腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白通路改善糖尿病肾脏疾病的研究  

α-lipoic acid ameliorates diabetic kidney disease via activating AMPK/mTOR pathway

作　　者：邱轩[1] 季虹 陈雅洁 田思宇 阎红伶 刘宽芝[1] QIU Xuan;JI Hong;CHEN Yajie(Department of Endocrinology,Third Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第三医院内分泌科,石家庄050000 [2]沧州市中心医院糖尿病内分泌四科 [3]河北医科大学研究生学院

出　　处：《中国糖尿病杂志》2021年第12期916-922,共7页Chinese Journal of Diabetes

基　　金：河北省自然科学基金(H2020206490);河北省医学科学研究课题计划项目(20190640);河北省政府资助省级临床医学优秀人才项目(2019年)。

摘　　要：目的探讨α-硫辛酸(LA)通过激活腺苷酸活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)通路改善T2DM大鼠肾脏病变。方法 40只大鼠分为正常对照组(Con)、T2DM组、LA组、复合物C组(Comp C)和LA+Comp C组,每组各8只。检测各组大鼠FPG、24 h尿蛋白水平,计算肾脏肥大指数,光镜和电镜观察大鼠肾脏病理变化,Weatern blot检测大鼠肾脏相关蛋白表达水平。结果与NC组比较,T2DM组FPG、肾脏肥大指数、24 h尿蛋白升高(P<0.01),光镜和电镜下均可见肾脏组织病变严重,p-AMPK、哺乳动物ATG6同源蛋白(Beclin-1)、微管相关蛋白1轻链3B(LC3B)II蛋白表达降低(P<0.01),p-mTOR、p62蛋白表达升高(P<0.05或P<0.01)。与T2DM组比较,LA组肾脏肥大指数、24 h尿蛋白降低(P<0.01),肾脏病理学改变有所改善,p-AMPK、Beclin-1、LC3BII蛋白表达增加(P<0.05或P<0.01),p-mTOR、p62蛋白表达减少(P<0.05或P<0.01)。与LA组比较,LA+Comp C组p-AMPK、Beclin-1、LC3BII水平降低(P<0.05或P<0.01),p-mTOR、p62水平升高(P<0.05或P<0.01)。结论 T2DM大鼠肾脏组织中AMPK/mTOR通路受抑制,应用LA可激活此通路,延缓DKD进展。Objective To assess the effect of α-lipoic acid(LA)in ameliorating kidney injury in diabetic rats via activating adenosine 5’-monophosphate-activate protein kinase(AMPK)/mammalian target of rapamycin(m TOR)pathway.Methods Forty rats were divided into normal control group(Con),T2 DM group,LA group,Compound C treatment group(Comp C)and LA+Comp C group,with 8 rats in each group.The levels of FPG,24-hour urine protein were detected.The kidney hypertrophy index was calculated.The expression levels of related proteins in rat kidney were detected by light and electron microscopy.Results Compared with NC group,FPG,renal hypertrophy index and 24-hour urinary protein in T2 DM group increased(P<0.01),and renal tissue lesions were serious under light and electron microscope.The expressions of p-AMPK,Beclin-1 and LC3 BII protein decreased(P<0.01).The expressions of p-m TOR and p62 protein increased(P<0.05 or P<0.01).Compared with T2 DM group,renal hypertrophy index and24-hour urinary protein in LA group decreased(P<0.01),renal pathological changes improved,and theexpressions of p-AMPK,Beclin-1 and LC3 BII increased(P<0.05 or P<0.01),while the expressions of p-m TOR and p62 decreased(P<0.05 or P<0.01).Compared with LA group,the levels of p-AMPK,Beclin-1 and LC3 BII in LA + Comp C group decreased(P<0.05 or P<0.01),while the levels of p-m TOR and p62 increased(P<0.05 or P<0.01).Conclusion AMPK/m TOR pathway was inhibited in the kidney of rats with T2 DM.LA could activate AMPK/m TOR pathway and delay the progression of diabetic nephropathy.

关 键 词：Α-硫辛酸 糖尿病 2型 糖尿病肾脏疾病 腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白通路 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]