中药“消渴汤”对糖尿病肾病大鼠的肾组织中COX-2和LDLr表达的影响  

The Effects of Xiaoke Decoction on the Expressions of COX-2 and LDLR in Renal Tissue of Diabetic Nephropathy Rats

作　　者：汤志奇[1] 陶灵佳 袁喆萍 王骞[1] 龚学忠[1] TANG Zhiqi;TAO Lingjia;YUAN Zheping(Department of Nephrology,Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,200071)

机构地区：[1]上海中医药大学附属市中医医院肾病科,上海200071

出　　处：《中国中西医结合肾病杂志》2020年第6期476-480,I0004,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：上海中医药大学预算内项目(No.18LK058)。

摘　　要：目的:探究中药“消渴汤”对糖尿病肾病(DN)大鼠的肾组织中环氧化酶2(COX-2)和低密度脂蛋白受体(LDLr)表达的影响。方法:选取6周龄健康雄性Wistar大鼠,采用高糖高脂饲料饲养联合一次性腹腔注射STZ方法制备DN大鼠模型,随机分为模型组、缬沙坦组(0.04 g·kg^-1·d^-1灌胃)、消渴汤低(1.5 g·kg^-1·d^-1灌胃)、中(3.0 g·kg^-1·d^-1灌胃)、高剂量(6.0 g·kg^-1·d^-1灌胃)组,另取正常大鼠为对照组,每组10只,模型组与对照组给予等量生理盐水灌胃,连续灌药12周。12周末,检测空腹血糖(FPG)、收集24 h尿液检测尿微量白蛋白(UmALB)、尿总蛋白(UTP),采集血清标本检测三酰甘油(TG)、总胆固醇(TC)、血肌酐(Scr)、血尿素氮(BUN)水平,采集肾组织光镜下观察肾脏HE染色病理变化,电镜下观察肾小球足细胞病理结构变化,采用免疫印迹(WB)检测肾组织中COX-2、LDLr蛋白表达。结果:与对照组比较,模型组大鼠UmALB、UTP、FPG、血清TG、Scr、BUN水平、肾组织COX-2和LDLr蛋白表达水平均显著增加(P<0.05);与模型组比较,缬沙坦组、消渴汤低、中、高剂量组大鼠UmALB、UTP、FPG、血清TG、Scr、BUN水平、肾组织COX-2和LDLr蛋白表达水平均降低(P<0.05);与模型组比较,消渴汤呈剂量依赖性下调大鼠尿UmALB、UTP、FPG、血清TG、Scr、BUN水平、肾组织COX-2和LDLr蛋白表达水平,肾小球系膜病变及足细胞损伤明显减轻,且高剂量组优于缬沙坦组(P<0.05)。结论:中药“消渴汤”可减轻DN大鼠肾小球足细胞损伤,改善糖尿病肾病大鼠糖脂代谢及提高肾功能情况,这可能与下调肾组织COX-2、LDLr蛋白表达有关。Objective:To investigate the effects of Xiaoke Decoction on the expressions of cyclooxygenase-2(COX-2)and low density lipoprotein receptor(LDLR)in renal tissue of diabetic nephropathy(DN)rats.Methods:Six-week-old healthy male Wistar rats were used to establish DN model by High sugar and high fat feed combination one-time intraperitoneal injection of STZ,and they were randomly divided into model group,valsartan group(0.04 g·kg^-1·d^-1 by irrigation),Xiaoke Decoction low(1.5 g·kg^-1·d^-1 by irrigation),medium(3.0 g·kg^-1·d^-1 by irrigation)and high dose(6.0 g·kg^-1·d^-1 by irrigation)groups,in addition,take the normal rats as the control group,with 10 rats in each group,the model group and the control group were given the same amount of normal saline by gavage for 12 weeks.At the end of 12 weeks,fasting blood glucose(FPG)was measured,24 hours urine was collected to detect urine microalbumin(UmALB)and total protein(UTP),serum samples were collected to detect the levels of triglyceride(TG),total cholesterol(TC),serum creatinine(Scr),blood urea nitrogen(BUN),the pathological changes of HE staining were observed under light microscope,the pathological changes of glomerular podocytes were observed under electron microscope,and the expressions of COX-2 and LDLR in renal tissue were detected by Western blotting(WB).Results:Compared with the control group,UmALB,UTP,FPG,levels of serum TG,Scr,BUN,expressions of COX-2 and LDLR proteins in renal tissue of the model group were significantly increased(P<0.05).Compared with the model group,UmALB,UTP,FPG,levels of serum TG,Scr,BUN,expressions of COX-2 and LDLR proteins in renal tissue of rats in valsartan group and Xiaoke Decoction low,middle and high dose groups were decreased(P<0.05).Compared with the model group,UmALB,UTP,FPG,levels of serum TG,Scr,BUN,expressions of COX-2 and LDLR proteins of rats in Xiaoke Decoction groups decreased in a dose-dependent manner,glomerular mesangial lesions and podocyte damage were significantly reduced,and the high dose group was bette

关 键 词：糖尿病肾病 消渴汤 肾小球足细胞 环氧化酶2 低密度脂蛋白受体 

分 类 号：R285.5[医药卫生—中药学]