基于TGF-β/SMAD和VEGF通路探讨益气解毒通络方对2型糖尿病大鼠肾损伤的影响  

Effects of Yiqi Jiedu Tongluo Formula on renal injury in a rat model of type 2 diabetes mellitus via TGF-β/SMAD and VEGF pathways

作　　者：徐文轩 马雷雷 申明宇 喇孝瑾 张碧溦 王硕 李超 崔鹏 陈震 李继安 XU Wen-xuan;MA Lei-lei;SHEN Ming-yu;LA Xiao-jin;ZHANG Bi-wei;WANG Shuo;LI Chao;CUI Peng;CHEN Zhen;LI Ji-an(College of Traditional Chinese Medicine,North China University of Science and Technology,Tangshan 063200,China;School of Public Health,North China University of Science and Technology,Tangshan 063200,China;Tangshan Central Hospital,Tangshan 063000,China;Oriental Herbs KFT(Hungary),Budapest 1016,Hungary)

机构地区：[1]华北理工大学中医学院,河北唐山063200 [2]华北理工大学公共卫生学院,河北唐山063200 [3]唐山市中心医院,河北唐山063000 [4]匈牙利东方国药集团,布达佩斯匈牙利1016

出　　处：《中成药》2025年第2期421-429,共9页Chinese Traditional Patent Medicine

基　　金：科技部对发展中国家常规性科技援助项目(KY201904005);河北省中医药联合基金重点项目(H2023209038)。

摘　　要：目的观察益气解毒通络方对2型糖尿病(T2DM)大鼠肾脏微血管内皮功能及肾损伤的影响。方法将SD大鼠随机分为正常组和造模组,造模组采用高脂饲料联合单次腹腔注射STZ建立T2DM模型。将造模成功大鼠随机分为模型组、卡格列净组(9 mg/kg)和益气解毒通络方低、高剂量组(4.77、9.45 g/kg),灌胃给予相应剂量药物,共给药12周。给药期间观察大鼠一般情况及血糖变化;给药结束后测定大鼠肾脏指数、24 h UP及血清SCr、BUN、TC、TG、HDL-C、LDL-C、ET-1、NOS水平;HE染色、Masson染色、PAS染色和PASM染色观察大鼠肾脏微血管变化及肾脏纤维化程度;透射电镜观察大鼠肾小球超微结构;免疫组织化学染色和Western blot法检测肾组织TGF-β、SMAD2、SMAD3、Col-1、VEGFA、PKC蛋白表达;RT-qPCR法检测肾组织VEGFA、TGF-β、SMAD 2 mRNA表达。结果与模型组比较,益气解毒通络方高剂量组大鼠肾脏指数、血糖、TG、TC、HDL、24 h UP、BUN、SCr、ET-1水平降低(P<0.05,P<0.01),LDL、NOS水平升高(P<0.05,P<0.01);肾组织炎性浸润及纤维化程度减轻,足突融合及基底膜增厚现象得到抑制;肾组织TGF-β、SMAD2、SMAD3、VEGFA、PKC、Col-1蛋白表达降低(P<0.05,P<0.01),VEGFA、TGF-β、SMAD 2 mRNA表达降低(P<0.01)。结论益气解毒通络方能降低T2DM大鼠血糖、血脂水平,改善肾脏指数及肾脏微血管内皮功能指数,抑制肾脏微血管病变及肾脏纤维化,其机制可能与下调TGF-β/SMAD、VEGF通路相关蛋白表达有关。AIM To observe the effects of Yiqi Jiedu Tongluo Formula(YQJDTL)on renal microvascular endothelial function and prevention of renal injury in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly divided into a normal group and a model group.The model group was administered with high-fat diet combined with a single intraperitoneal injection of STZ to establish the T2DM model.The successfully modeled rats were randomly divided into the model group,the canagliflozin group(9 mg/kg),and the low-dose and high-dose YQJDTL groups(4.77,9.45 g/kg).The corresponding doses of the drug were administered by gavage for a total of 12 weeks,during which the rats underwent observation of their general condition and blood glucose changes.After the end of administration,the rats had their levels of renal index,24-hour UP,serum SCr,BUN,TC,TG,HDL-C,LDL-C,ET-1 and NOS measured;their changes in renal microvasculature and the degree of renal fibrosis observed using HE staining,Masson staining,PAS staining,and PASM staining;their ultrastructure of the glomeruli observed using transmission electron microscopy;their renal protein expressions of TGF-β,SMAD2,SMAD3,Col-1,VEGFA and PKC detected by immunohistochemical staining and Western blot;and their renal mRNA expressions of VEGFA,TGF-β,SMAD2 determined by RT-qPCR.RESULTS Compared with the model group,the high-dose YQJDTL group showed decreased levels of renal index,blood glucose,TG,TC,HDL,24 h UP,BUN,SCr and ET-1(P<0.05,P<0.01);increased LDL and NOS levels(P<0.05,P<0.01);reduced renal inflammatory infiltration and fibrosis degree,inhibited fusion of foot processes and thickening of basement membrane;decreased renal protein expressions of TGF-β,SMAD2,SMAD3,VEGFA,PKC and Col-1(P<0.05,P<0.01);and decreased mRNA expressions of VEGFA,TGF-βand SMAD2(P<0.01).CONCLUSION In the rat models of T2DM,YQJDTL can reduce their levels of blood glucose and lipids by improving the renal indices levels and the renal microvascular endothelial functions to alleviate renal fibrosis

关 键 词：益气解毒通络方 2型糖尿病 肾脏损伤 血管内皮功能 肾脏纤维化 TGF-β/SMAD通路 VEGF通路 

分 类 号：R285.5[医药卫生—中药学]