玉泉丸对糖尿病肾病大鼠AMPK/FOXO3a通路及肾损伤的影响  

Effects of Yuquan Pill on AMPK/FOXO3a Pathway and Renal Structure Damage in Diabetic Nephropathy Rats

作　　者：郭逸[1] 华川[1] 裴迅[1] 谢敏 黄海[2] GUO Yi;HUA Chuan;PEI Xun(Department of Endocrinology,Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430070)

机构地区：[1]湖北省中医院内分泌科,武汉430070 [2]湖北省中医院推拿科,康复医学科,武汉430070

出　　处：《中国中西医结合肾病杂志》2021年第11期954-958,I0001,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：湖北省卫生健康委员会基金资助项目(No.ZY2019M046)。

摘　　要：目的:探究玉泉丸对糖尿病肾病(DN)大鼠肾损伤及腺苷酸活化蛋白激酶(AMPK)/叉头框转录因子3a(FoxO3a)通路的影响。方法:90只大鼠随机选取12只为空白组,其余大鼠采用高脂高糖膳食辅以链脲佐菌素腹腔注射构建DN模型。筛选模型成功大鼠60只分为DN组、二甲双胍组(0.045 g/kg),玉泉丸高、中、低剂量组(8.64、4.32、2.16 g/kg),每组12只。各给药组分别灌胃给予相应的药物,1次/d,连续给药8周。检测大鼠24 h尿微量白蛋白(U-mAlb)水平;血糖仪检测空腹血糖(FBG)水平;计算肾脏指数;并检测血清肌酐(Scr)、尿素氮(BUN)水平和肾组织匀浆中活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)含量;HE染色观察肾脏组织形态变化;荧光显微镜观察肾脏组织凋亡情况;Western blot检测肾脏AMPK、FOXO3a及其磷酸化蛋白表达。结果:与空白组相比,DN组大鼠肾小管上皮细胞损伤严重,大鼠FBG、U-mAlb、血清Scr、BUN、肾脏指数、肾脏组织ROS、MDA、肾小管上皮细胞凋亡数量显著升高(P<0.05),体重、肾脏组织SOD、CAT、p-AMPK/AMPK、p-FOXO3a/FOXO3a蛋白表达显著降低(P<0.05);与DN组相比,二甲双胍组和玉泉丸高、中剂量组大鼠肾脏组织病理损伤明显减轻,FBG、U-mAlb、血清Scr、BUN水平、肾脏指数、肾脏组织ROS、MDA、肾小管上皮细胞凋亡数量明显下降(P<0.05),体重、肾脏组织SOD、CAT含量、p-AMPK/AMPK、p-FOXO3a/FOXO3a蛋白表达明显升高(P<0.05)。结论:玉泉丸可能通过激活AMPK/FOXO3a通路抑制DN大鼠氧化应激反应和肾脏细胞凋亡,减轻肾损伤。Objective:To explore the effects of Yuquan Pill on renal structure damage and the expression of AMP-activated protein kinase(AMPK)/forkhead box 3a(FOXO3a)pathway in diabetic nephropathy(DN)rats.Methods:The 12 of 90 rats were randomly selected as blank group.The rest rats were fed with high-fat and high sugar diet supplemented with intraperitoneal injection of streptozotocin to establish diabetic nephropathy rat model.The successfully 60 rats were divided into DN group,metformin group(0.045 g/kg),Yuquan Pill high,medium and low dose groups(8.64,4.32,2.16 g/kg),with 12 rats in each group.Each administration groups were given corresponding drugs by gavage,once a day,continuous administration for 8 weeks.The levels of 24 h urinary microalbumin(U-mAlb)were measured;fasting blood glucose(FBG)was measured by blood glucose meter;renal index was calculated;the levels of serum creatinine(Scr)and urea nitrogen(BUN)and reactive oxygen species(ROS),superoxide dismutase(SOD),malondialdehyde(MDA)and catalase(CAT)in renal tissue homogenate were detected;HE staining was used to observe the morphological changes of kidney tissue;the apoptosis of kidney tissue was observed by fluorescence microscope;Western blot was used to detect the expression of AMPK,FOXO3a and phosphorylated protein in kidney.Results:Compared with those in the blank group,the injury of renal tubular epithelial cells in DN group was serious,FBG,U-mAlb,serum Scr,BUN,renal index,ROS,MDA in renal tissue and apoptosis of renal tubular epithelial cells were significantly higher(P<0.05),body weight,SOD,CAT,p-AMPK/AMPK,p-FOXO3a/FOXO3a protein expression were significantly lower(P<0.05);compared with those in DN group,the pathological damage of kidney tissue in metformin group and Yuquan Pill high and medium dose groups was significantly reduced,the levels of FBG,U-mAlb,serum Scr,BUN,renal index,ROS,MDA in renal tissue and apoptosis of renal tubular epithelial cells were significantly lower(P<0.05),body weight,SOD,CAT contents,p-AMPK/AMPK,p-FOXO3a/FOXO3a protein express

关 键 词：糖尿病肾病 玉泉丸 氧化应激 腺苷酸活化蛋白激酶/叉头框转录因子3a 凋亡 

分 类 号：R285.5[医药卫生—中药学]