葛根芩连汤加味方改善糖尿病肾病模型鼠足细胞焦亡和胰岛素抵抗的作用和机制  

Effects and mechanisms of Supplemented Gegen Qinlian Decoction Formula against podocyte pyroptosis and insulin resistance in model rats with diabetic kidney disease

作　　者：王美子 岳丽军[2] 万毅刚[2] 黄煌 吴薇[2] 涂玥 刘不悔 房其军[1] 袁灿灿 王杰[1] 李欢[1] WAN Zi-yue WANG Mei-zi;YUE Li-jun;WAN Yi-gang;HUANG Huang;WU Wei;TU Yue;LIU Bu-hui;FANG Qi-jun;YUAN Can-can;WANG Jie;LI Huan;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,The Affiliated Hospital of Medical School of Nanjing University,Nanjing 210008,China;School of International Classical Prescription,Nanjing University of Chinese Medicine,Nanjing 210023,China;School of Acupuncture-Moxibustion and Tuina&School of Health Preservation and Rehabilitation,Nanjing University of Chinese Medicine,Nanjing 210023,China;Department of Nephrology,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,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]南京中医药大学国际经方学院,江苏南京210023 [4]南京中医药大学针灸推拿学院·养生康复学院中医养生学教研室,江苏南京210023 [5]南京中医药大学附属医院肾内科,江苏南京210029 [6]Graduate School of Social Sciences,Faculty of Social Sciences,Hitotsubashi University,Tokyo 186-8601

出　　处：《中国中药杂志》2021年第17期4471-4479,共9页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81573903);国家自然科学基金青年基金项目(81603675);江苏省自然科学基金青年基金项目(BK20161046);中央高校基本科研业务费专项(021414380518);江苏高校优势学科建设工程项目(PAPD);江苏省研究生科研与实践创新计划项目(KYCX211699,KYCX211712,SJCX210672,KYCX201546);南京中医药大学中医学优势学科三期项目开放课题(ZYX03KF016);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：为了探究现代经方——葛根芩连汤加味方(Supplemented Gegen Qinlian Decoction Formula,SGDF)在体内改善糖尿病肾病(diabetic kidney disease,DKD)的作用和机制,将60只大鼠随机分为正常组、模型组、SGDF组和罗格列酮(rosiglitazone,ROS)组。通过"高脂饲料喂养+单侧肾切除+链脲佐菌素(streptozocin,STZ)腹腔注射"等3种措施建立改良型大鼠DKD模型。成模后,对于4组大鼠,每天经灌胃分别给予其双蒸水、SGDF混悬液以及ROS混悬液。在药物干预第6周末,处死全部大鼠,收集尿液、血液以及肾组织,进而,针对DKD足细胞焦亡和胰岛素抵抗(insulin resistance,IR)相关的各项指标进行检测和观察。这些指标包括各组大鼠一般情况,尿液、血液生化指标,肾小球硬化相关指标,足细胞焦亡标志分子,IR相关指标以及肾组织胰岛素受体底物(insulin receptor substrate,IRS)1/磷脂酰肌醇3激酶(phosphatidylinositol3-kinase,PI3K)/丝氨酸-苏氨酸激酶(serine-threonine kinase,Akt)信号通路关键信号分子等。结果显示,对于DKD模型鼠,SGDF和ROS尽管对血糖(blood glucose,BG)无影响,但是都能改善其一般状况、部分肾功能指标以及肾小球硬化;都能改善其足细胞焦亡标志分子的表达特征和表达水平;此外,还能改善其肾组织IR,并不同程度地上调其肾组织IRS1/PI3K/Akt信号通路关键信号分子蛋白表达水平。总之,SGDF与ROS相似,在体内能多靶点地改善DKD,其机制与减轻足细胞焦亡和IR有关;该研究为现代经方——SGDF治疗DKD新药研究与开发提供了初步的药理学证据。This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF)against diabetic kidney disease(DKD).Sixty rats were randomly divided into the normal group,model group,SGDF group,and rosiglitazone(ROS)group.The modified DKD rat model was established by employing the following three methods:exposure to high-fat diet,unilateral nephrectomy,and intraperitoneal injection of streptozotocin(STZ).After modeling,rats in the four groups were treated with double distilled water,SGDF suspension,and ROS suspension,respectively,by gavage every day.At the end of the 6 th week of drug administration,all the rats were sacrificed for collecting urine,blood,and kidney tissue,followed by the examination of rat general conditions,urine and blood biochemical indicators,glomerulosclerosis-related indicators,podocyte pyroptosis markers,insulin resistance(IR)-related indicators,and key molecules in the insulin receptor substrate(IRS)1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt)signaling pathway.The results showed that SGDF and ROS improved the general conditions,some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG).Besides,they ameliorated the expression characteristics and levels of podocyte pyroptosis markers,alleviated IR,and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees.In conclusion,similar to ROS,SGDF relieves DKD by targeting multiple targets in vivo.Specifically,it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR.This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.

关 键 词：糖尿病肾病 葛根芩连汤加味方 足细胞焦亡 胰岛素抵抗 胰岛素信号通路 

分 类 号：R285.5[医药卫生—中药学]