化瘀通络中药通过调控AMPK/mTOR通路激活自噬改善糖尿病肾病大鼠肾损伤  

Huayu Tongluo Chinese medicines activating autophagy by regulating AMPK/mTOR pathway to improve renal injury in diabetic nephropathy rats

作　　者：张西巧 张学琴 马赟 刘子岳 李靓 陈志强 ZHANG Xiqiao;ZHANG Xueqin;MA Yun;LIU Ziyue;LI Liang;CHEN Zhiqiang(Graduate School,Hebei University of Chinese Medicine,Shijiazhuang 050091,China;The First Affiliated Hospital of Hebei University of Chinese Medicine,Shijiazhuang 050000,China;Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Liver and Kidney Disease Research,Shijiazhuang 050091,China;Hebei Technology Innovation Center of Traditional Chinese Medicine Spleen and Kideney Diseaes,Shijiazhuang 050000,China)

机构地区：[1]河北中医药大学研究生院,石家庄050091 [2]河北中医药大学第一附属医院,石家庄050000 [3]河北中西医结合肝肾病证研究重点实验室,石家庄050091 [4]河北省脾肾病症中医治疗技术创新中心,石家庄050000

出　　处：《天津中医药》2025年第5期656-661,共6页Tianjin Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82274504);河北省中医药管理局科研计划项目(2020039);河北省高等学校科学技术研究项目(QN2023100)。

摘　　要：[目的]探讨化瘀通络中药对糖尿病肾病(DN)大鼠肾脏的治疗作用及其作用机制。[方法]将大鼠随机分为造模组30只和对照组10只,造模组摘除右侧肾脏+腹腔注射链脲佐菌素(1%,40 mg/kg),成模后的大鼠随机分成模型组10只、化瘀通络中药组10只、厄贝沙坦组10只。给药12周后检测大鼠糖化白蛋白(GA)、胆固醇(TC)、三酰甘油(TG)、尿素氮(BUN)、肌酐(Scr)以及24 h尿蛋白(24 h UTP)水平;光镜观察大鼠肾组织病理形态学变化;蛋白免疫印迹法检测大鼠肾组织螯合体1(SQSTM1/p62)、人微管相关蛋白轻链3B-Ⅱ(LC3B-Ⅱ)/人微管相关蛋白轻链3B-Ⅰ(LC3B-Ⅰ)、腺苷酸活化蛋白激酶(AMPK)、磷酸化腺苷酸活化蛋白激酶(p-AMPK)、雷帕霉素哺乳靶蛋白(mTOR)、磷酸化雷帕霉素哺乳靶蛋白(p-mTOR)表达水平。[结果]与对照组比较,模型组大鼠血清GA、TC、TG、BUN及24 h UTP水平显著升高,肾组织出现明显病理损伤,肾组织p-AMPK/AMPK、LC3B-Ⅱ/LC3B-Ⅰ表达降低,p-mTOR/mTOR、p62表达升高(P<0.05或P<0.01);与模型组比较,经化瘀通络中药干预后,DN大鼠血清TC、TG、BUN及24 h UTP水平降低,肾组织病理损伤得到改善,肾组织LC3B-Ⅱ/LC3B-Ⅰ、p-AMPK/AMPK表达升高,p62、p-mTOR/mTOR表达降低(P<0.05或P<0.01)。[结论]化瘀通络中药可减轻肾脏损伤,延缓肾功能下降,其潜在作用机制可能与调控AMPK/mTOR信号通路介导的自噬有关。[Objective]To investigate the therapeutic effect of the traditional Chinese medicine of resolving blood stasis and promoting collaterals on the kidneys of rats with diabetic nephropathy(DN)and its mechanism of action.[Methods]The rats were randomly divided into 30 rats in the modeling group and 10 rats in the control group.The modeling group had the right kidney removed+streptozotocin(1%,40 mg/kg)injected intraperitoneally,and the modeled rats were randomly divided into 10 rats in the model group,10 rats in the group of traditional Chinese medicines for resolving blood stasis and clearing the channels and 10 rats in the group of Irbesartan.After 12 weeks of drug administration,the levels of glycated albumin(GA),cholesterol(TC),triacylglycerol(TG),urea nitrogen(BUN),creatinine(Scr),and 24-hour urinary protein(24 h UTP)were measured;the pathological and morphological changes of the renal tissues of the rats were observed by light microscopy;the levels of SQSTM1/p62,human microtubule-associated protein light chain(LC3B-Ⅱ),human microtubule-associated protein light chain(LC3B-Ⅱ),and human microtubule-associated protein light chain(LC3B-Ⅱ)were detected by immunoblotting.3B-Ⅱ(LC3B-Ⅱ)/human microtubule-associated protein light chain 3B-Ⅰ(LC3B-Ⅰ),adenylate-activated protein kinase(AMPK),phosphorylated adenylate-activated protein kinase(p-AMPK),mammalian target of rapamycin(mTOR),and phosphorylated mammalian target of rapamycin(p-mTOR).[Results]Compared with the control group,serum GA,TC,TG,BUN and 24 h UTP levels were significantly increased in the model group,renal tissue showed obvious pathological damage,renal tissue p-AMPK/AMPK,LC3B-Ⅱ/LC3B-Ⅰexpression was decreased,and p-mTOR/mTOR,p62 expression was elevated(P<0.05 or P<0.01);compared with the model group,DN rats had decreased serum TC,TG,BUN and 24 h UTP levels and improved renal tissue pathological damage after intervention with the traditional Chinese medicine of resolving blood stasis and promoting circulation.Compared with the model group,after

关 键 词：糖尿病肾病 化瘀通络中药 自噬 AMPK/mTOR信号通路 

分 类 号：R285.5[医药卫生—中药学]