基于IRS1/PI3K/Akt通路探究黄蜀葵花总黄酮改善糖尿病肾脏疾病胰岛素抵抗和足细胞转分化的作用和机制  

Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway

作　　者：王玉[1,2,3] 曹东维[4] 万毅刚[2] 穆耕林 吴薇[2] 房其军 李雅静[1] 察思雨[1] 涂玥 WAN Zi-yue WANG Yu;CAO Dong-wei;WAN Yi-gang;MU Geng-lin;WU Wei;FANG Qi-jun;LI Ya-jing;CHA Si-yu;TU Yue;WAN Zi-yue(Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine,Nanjing 210008,China;Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University,Nanjing 210008,China;Institute of Chinese Medicine,Nanjing University,Nanjing 210008,China;Department of Nephrology,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Acupuncture,Moxibustion and Massage College,Health Preservation and Rehabilitation College,Nanjing University of Chinese Medicine,Nanjing 210032,China;Graduate School of Social Sciences,Faculty of Social Sciences,Hitotsubashi University,Tokyo 186-8601,Japan)

机构地区：[1]南京中医药大学鼓楼临床医学院中医科,江苏南京210008 [2]南京大学医学院附属鼓楼医院中医科,江苏南京210008 [3]南京大学中医研究院,江苏南京210008 [4]上海中医药大学附属市中医医院肾病科,上海200071 [5]南京中医药大学针灸推拿学院·养生康复学院,江苏南京210023 [6]Graduate School of Social Sciences,Faculty of Social Sciences,Hitotsubashi University,Tokyo,186-8601,Japan

出　　处：《中国中药杂志》2023年第10期2646-2656,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(82174472、81573903);江苏省自然科学基金面上项目(BK20211298);江苏省中医药科技发展计划项目(MS2021037);江苏省研究生科研与实践创新计划项目(KYCX22_2065);南京中医药大学自然科学基金项目(XZR2021087);南京市医学科技发展项目(YKK20085);南京市名中医专家工作室建设项目。

摘　　要：为了探究传统治肾中药黄蜀葵花的提取物——黄蜀葵花总黄酮(total flavones of Abelmoschus manihot,TFA)在体内改善糖尿病肾脏疾病(diabetic kidney disease,DKD)胰岛素抵抗(insulin resistance,IR)和足细胞转分化(epithelial-mesenchymal transition,EMT)的作用和机制,并进一步揭示其科学内涵,将32只大鼠随机分为正常组、模型组、TFA组和罗格列酮(rosiglitazone,ROS)组。通过“高脂饲料饲养、单肾切除以及STZ腹腔注射”等综合措施联合诱导改良型DKD大鼠模型。成模后,对于4组大鼠,每天经灌胃分别给予其双蒸水、TFA混悬液以及ROS混悬液。在中、西药物干预的第8周末,处死全部大鼠,收集尿液、血液以及肾组织等标本,进而针对DKD模型鼠IR和足细胞EMT相关的各项参数和指标进行检测和观察,包括大鼠一般情况,体质量(body weight,BW)及肾脏质量(kidney weight,KW),生化参数和IR指标,肾组织胰岛素受体底物(insulin receptor substrate,IRS)1/磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)/丝氨酸-苏氨酸激酶(serine-threonine kinase,Akt)通路关键信号分子和裂隙膜结构分子蛋白表达水平,足突形态和肾小球基底膜(glomerular basement membrane,GBM)厚度,足细胞EMT标志分子和裂隙膜结构分子的表达程度以及肾小球组织形态特征等。结果显示,首先,对于DKD模型鼠,TFA和ROS均能改善一般情况、部分生化参数、肾脏外观和KW;然后对于BW、尿白蛋白(urinary albumin,UAlb)/尿肌酐(urinary creatinine,UCr)、血清肌酐(serum creatinine,Scr)、血清甘油三酯(triglyceride,TG)、KW的改善作用,TFA和ROS相似;再者,两者均能改善IR指标,其中,对于空腹血清胰岛素(fast insulin,FIN)、IR指数(homeostasis model assessment of insulin resistance,HOMA-IR)的改善作用,ROS优于TFA;其次,两者均能不同程度地改善肾组织IRS1/PI3K/Akt通路关键信号分子的蛋白表达水平和肾小球硬化,而且TFA的改善作用和ROS相似;最后This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA),the extracts from traditional Chinese herbal medicine(CHM)indicated for kidney diseases,on insulin resistance(IR)and podocyte epithelial-mesenchymal transition(EMT)in diabetic kidney disease(DKD),and further to reveal the scientific connotation.Thirty-two rats were randomly divided into a normal group,amodel group,a TFA group,and arosiglitazone(ROS)group.The modified DKD model was induced in rats by methods including high-fat diet feeding,unilateral nephrectomy,and streptozotocin(STZ)intraperitoneal injection.After modeling,the rats in the four groups were given double-distilled water,TFA suspension,and ROS suspension correspondingly by gavage every day.At the end of the 8th week of drug administration,all rats were sacrificed,and the samples of urine,blood,and kidney tissues were collected.The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed,including the general condition,body weight(BW)and kidney weight(KW),the biochemical parameters and IR indicators,the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS)1/phosphatidylinositol3-kinase(PI3K)/serine-threonine kinase(Akt)pathway,foot process morphology and glomerular basement membrane(GBM)thickness,the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT,and glomerular histomorphological characteristics.The results showed that for the DKD model rats,both TFA and ROS could improve the general condition,some biochemical parameters,renal appearance,and KW.The ameliorative effects of TFA and ROS were equivalent on BW,urinary albumin(UAlb)/urinary creatinine(UCr),se rum creatinine(Scr),triglyceride(TG),and KW.Secondly,they could both improve IR indicators,and ROS was superior to TFAin improving fast insulin(FIN)and homeostasis model assessment of insulin resistance(HOMA-IR).Thirdl

关 键 词：黄蜀葵花总黄酮 糖尿病肾脏疾病 胰岛素抵抗 足细胞转分化 IRS1/PI3K/Akt通路 

分 类 号：R285.5[医药卫生—中药学]