玉泉丸对糖尿病肾病大鼠GSK⁃3β/Nrf2通路及YKL⁃40表达的影响  

Effects of Yuquan Pills on GSK⁃3β/Nrf2 pathway and YKL⁃40 expression in diabetic nephropathy rats

作　　者：陈烨 贾崇高 唐英骞 王昱 CHEN Ye;JIA Chong-gao;TANG Ying-qian;WANG Yu(Department of Nephrology,The Hospital Affiliated to Guizhou Medical University,Guizhou 550004,China)

机构地区：[1]贵州医科大学附属医院肾内科,贵州贵阳550004

出　　处：《中成药》2022年第1期61-66,共6页Chinese Traditional Patent Medicine

基　　金：贵州省科技计划项目(黔科合LH字[2017]7183)。

摘　　要：目的探讨玉泉丸对糖尿病肾病大鼠GSK⁃3β/Nrf2通路及肾小球内皮损伤标志物YKL⁃40表达的影响。方法采用高脂高糖饲料喂养结合一次性腹腔注射链脲佐菌素制备大鼠糖尿病肾病模型,大鼠随机分为正常组,模型组,玉泉丸低、中、高(4、8、12 g/kg)剂量组和二甲双胍(50 mg/kg)组(阳性对照),每组10只。全自动生化分析仪检测血糖、甘油三酯、总胆固醇、肌酐、尿素和24 h尿微量白蛋白水平,HE染色观察肾组织病理学变化并评分,ELISA检测血清YKL⁃40、TNF⁃α、IL⁃6、内皮素(ET)水平及肾组织SOD、CAT活性和MDA水平,免疫组织化学法检测肾组织YKL⁃40表达,Western blot检测肾组织GSK⁃3β、p⁃GSK⁃3β、Nrf2蛋白表达。结果与正常组比较,模型组大鼠肾组织病理学评分,血糖,甘油三酯、总胆固醇、肌酐、尿素、24 h尿微量白蛋白水平,YKL⁃40、TNF⁃α、IL⁃6、ET、MDA水平和YKL⁃40阳性表达指数升高(P<0.01),SOD、CAT活性,p⁃GSK⁃3β/GSK⁃3β、Nrf2蛋白表达降低(P<0.01);与模型组比较,玉泉丸低、中、高剂量组和二甲双胍组大鼠肾组织病理学评分、血糖、甘油三酯、总胆固醇、肌酐、尿素、24 h尿微量白蛋白、YKL⁃40、TNF⁃α、IL⁃6、ET、MDA水平和YKL⁃40阳性表达指数降低(P<0.01),SOD、CAT活性、p⁃GSK⁃3β/GSK⁃3β和Nrf2蛋白表达升高(P<0.01)。结论玉泉丸可降低糖尿病肾病大鼠肾小球内皮损伤标志物YKL⁃40表达,减轻氧化应激和炎症反应,可能与激活GSK⁃3β/Nrf2通路有关。AIM To investigate the effects of Yuquan Pills on GSK⁃3β/Nrf2 pathway and the expression of glomerular endothelial damage marker YKL⁃40 in diabetic nephropathy(DN)rats.METHODS The DN rat models were established by feedings of high⁃fat and high⁃sugar diet combined with one intraperitoneal injection of streptozotocin(STZ).The rats were randomly divided into normal group,model group,Yuquan Pills groups for uses of low dose,medium dose and high dose pills(4,8,12 g/kg),and metformin positive control group(50 mg/kg),with 10 rats in each group.Subsequently,the rats were subjected to determination of levels of blood glucose,triglyceride,total cholesterol,creatinine,urea and 24 h urinary microalbumin by automatic biochemical analyzer;observation and scoring of their histopathological changes of kidney by HE staining;detection of their serum levels of YKL⁃40,TNF⁃α,IL⁃6 and endothelin(ET),and nephritic SOD and CAT activities and MDA level by ELISA;examination of their nephritic YKL⁃40 expression by immunohistochemistry,and detection of nephritic protein expressions of GSK⁃3β,p⁃GSK⁃3βand Nrf2 by Western blot.RESULTS Compared with the normal group,the model group was observed with increased renal histopathological score,higher levels of blood glucose,triglyceride,total cholesterol,creatinine,urea,24 h urinary microalbumin,YKL⁃40,TNF⁃α,IL⁃6,ET,MDA and positive expression index of YKL⁃40(P<0.01);decreased SOD and CAT activities,and reduced protein expressions of p⁃GSK⁃3β/GSK⁃3βand Nrf2(P<0.01).Compared with the model group,all Yuquan Pills groups and metformin positive group shared decreased renal histopathological score,lower levels of blood glucose,triglyceride,total cholesterol,creatinine,urea,24 h urinary microalbumin,YKL⁃40,TNF⁃α,IL⁃6,ET,MDA and positive expression index of YKL⁃40(P<0.01);increased SOD and CAT activities,and reduced protein expressions of p⁃GSK⁃3β/GSK⁃3βand Nrf2(P<0.01).CONCLUSION Yuquan Pills can reduce the expression of glomerular endothelial in

关 键 词：玉泉丸 糖尿病肾病 GSK⁃3β/Nrf2 YKL⁃40 

分 类 号：R285.5[医药卫生—中药学]