灯盏细辛联合依帕司他对糖尿病肾病模型大鼠的治疗作用及机制

目的:探讨基于多元醇通路(PP)中醛糖还原酶(AR)灯盏细辛联合依帕司他(EPST)对糖尿病肾病(DN)大鼠氧化应激以及肾功能的干预机制。方法:将50只SD大鼠,随机平均分为正常对照组以及各干预组(模型组、EPST组、灯盏细辛组和EPST+灯盏细辛组)。各干预组采用单次注射链脲佐菌素(STZ)55 mg/kg合并喂养高脂高糖饲料的方法制备大鼠DN模型。持续灌胃给药6周后,观察大鼠一般形态学变化; HE染色观察大鼠肾组织形态变化; 血糖仪检测空腹血糖(FBG)水平; 动物体重天平检测体重水平; 全自动生化仪检测血肌酐(Scr)和尿素氮(BUN)水平; 试剂盒检测肾组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)水平; ELISA检测24 h尿微量白蛋白(24 h UmAlb)和肾组织AR水平。结果:与正常对照组比较,模型组大鼠出现“三多一少”糖尿病典型症状,肾小球肥大,肾小管呈空泡样变性,FBG水平升高(P<0.01),体重水平降低(P<0.01),24 h UmAlb、Scr和BUN水平升高(P<0.01),SOD和GSH水平降低(P<0.01),MDA水平升高(P<0.01),AR活性升高(P<0.01)。与模型组比较,各给药组整体状态好转,肾组织病理结构损害显著降低,FBG水平降低(P<0.01),体重水平升高(P<0.01),24 h UmAlb、Scr和BUN水平降低(P<0.01),SOD和GSH水平升高(P<0.01),MDA水平降低(P<0.01),AR活性降低(P<0.01),而EPST+灯盏细辛组的作用显著优于EPST或灯盏细辛组(P<0.05)。结论:灯盏细辛与EPST联合给药能改善DN大鼠肾功能以及提高其抗氧化能力,且治疗效果优于单独给药组,其作用机制可能与通过下调肾组织AR活性来抑制PP的激活,并协同减轻肾组织氧化应激有关。

Therapeutic effect and mechanism of erigeron breviscapus combined with epalrestat on diabetic nephropathy model rats

Objective:To investigate the intervention mechanism of erviscapus breviscapus combined with epalrestat(EPST)on oxidative stress and renal function in early diabetic nephropathy(DN)rats based on polyol pathway(AR).Methods:Fifty SD rats were randomly divided into normal control group and intervention groups(model group,EPST group,erigeron group and EPST+erigeron group).The DN model of each intervention group was established.After continuous intragastric administration for 6 weeks,the general morphological changes of rats were observed.To observe the morphological changes of renal tissues in rats,The level of fasting blood glucose(FBG),To detect the body mass level,Serum creatinine(Scr)and urea nitrogen(BUN)levels.The levels of superoxide dismutase(SOD),malondialdehyde(MDA)and reduced glutathione(GSH)in renal tissue were detected by the kit.ELISA was used to detect 24 h urinary microalbumin(24 h UmAlb)and AR levels in renal tissue.Results:Compared with normal control group,model group showed typical symptoms of “three more and one less” diabetes mellitus,glomerular hypertrophy,vacuolar degeneration of renal tubules,increased FBG level(P<0.01),decreased body weight(P<0.01),increased 24 h UmAlb,Scr and BUN levels(P<0.01).The levels of SOD and GSH decreased(P<0.01),the level of MDA increased(P<0.01),and the activity of AR increased(P<0.01).Compared with model group,the overall status of each administration group was improved,the pathological structure damage of renal tissue was significantly decreased,the level of FBG was decreased(P<0.01),the level of body weight was increased(P<0.01),the levels of 24 h UmAlb,Scr and BUN were decreased(P<0.01),and the levels of SOD and GSH were increased(P<0.01).MDA level and AR activity were decreased(P<0.01),and the effect of EPST+erigeron group was significantly better than that of EPST or erigeron group(P<0.05).Conclusion:Combined administration of erigeron brecapus and EPST can improve renal function and antioxidant capacity of early DN rats,and the therapeutic effect is better than that of the single administration group.The mechanism of action may be related to inhibiting the activation of PP by down-regulating the activity of AR in renal tissue,and synergistic alleviation of oxidative stress in renal tissue.