葛根芩连汤调控SIRT1/PGC1α/Nrf1信号通路改善追赶生长大鼠糖脂代谢紊乱  

Gegen Qinliantang Ameliorates Glucose and Lipid Metabolism Disorders in Rat Model of Catch-up Growth by Regulating SIRT1/PGC1α/Nrf1 Signaling Pathway

作　　者：丁纪茹 张欢[2] 刘东敏[2] 张效科[2] DING Jiru;ZHANG Huan;LIU Dongmin;ZHANG Xiaoke(Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]成都中医药大学附属医院,成都610075 [2]陕西中医药大学,陕西咸阳712046

出　　处：《中国实验方剂学杂志》2024年第1期77-86,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81774304)。

摘　　要：目的:探讨葛根芩连汤对高脂饮食诱导追赶生长(CUG)大鼠糖脂代谢的影响及机制。方法:60只SD大鼠随机分为正常组(18只)和追赶生长模型组(42只),采用限制饮食后开放高脂饮食的方式建立追赶生长大鼠模型,观察大鼠一般状况、体质量的变化,分别于第4周、第8周末各组抽取6只大鼠检测空腹血糖(FBG)、空腹血清胰岛素(FINS)、甘油三脂(TG)、总胆固醇(TC)水平,并计算胰岛素抵抗指数(HOMA-IR),评估CUG大鼠胰岛素敏感性及体成分的改变。造模成功后,分别给予葛根芩连汤和吡格列酮干预6周,实验分为6组:正常组、模型组、葛根芩连汤低、中、高剂量组(2.5、5、10 g·kg^(-1))、吡格列酮组(3.125 mg·kg^(-1)),正常组和模型组给予等量生理盐水灌胃。实验过程中,记录大鼠体质量的变化,于实验结束时检测FBG、FINS、TG、TC水平,计算HOMA-IR指数;苏木素-伊红(HE)染色观察大鼠骨骼肌组织病理学改变;严格按照试剂盒所示方法检测骨骼肌活性氧(ROS)、丙二醛(MDA)水平;实时荧光定量聚合酶链式反应(Real-time PCR)检测骨骼肌沉默信息调节因子1(SIRT1)、过氧化物酶体增殖物激活受体γ共激活剂1α(PGC1α)、核因子E_2相关因子1(Nrf1)m RNA的表达;免疫组化法及蛋白免疫印迹法(Western blot)检测骨骼肌SIRT1、PGC1α、Nrf1蛋白的表达。结果:与正常组比较,模型组大鼠FBG有所升高,FINS、HOMA-IR显著升高(P<0.01);血清TG、TC水平明显升高(P<0.05,P<0.01);大鼠骨骼肌组织肌纤维直径显著增加,肌细胞间的脂肪细胞明显增加;骨骼肌ROS、MDA水平显著升高(P<0.01);SIRT1、PGC1α、Nrf1 m RNA及蛋白表达明显下降(P<0.05,P<0.01)。与模型组比较,葛根芩连汤各剂量组及吡格列酮组大鼠的体质量、FINS、HOMA-IR、TG水平显著降低(P<0.05,P<0.01),以葛根芩连汤中、高剂量组和吡格列酮组变化最明显;骨骼肌肌间脂肪等间质成分明显减少,肌纤维直径变窄;骨�Objective:To investigate the effect of Gegen Qinliantang on glucose and lipid metabolism in the rat model of catch-up growth(CUG)induced by a high-fat diet and the underlying mechanism.Method:A total of 60 SD rats were randomized into a normal control group(n=18)and a modeling group(n=42).The rat model of CUG was established with a restricted diet followed by a high-fat diet,and the changes of general status and body weight were observed.The levels of fasting blood glucose(FBG),fasting insulin(FINS),triglyceride(TG),and total cholesterol(TC)were measured in 6 rats in each group at the end of the 4th and 8th week,respectively.The homeostasis model assessment of insulin resistance index(HOMA-IR)was calculated,and the insulin sensitivity and body composition changes of CUG rats were evaluated.The successfully modeled rats were assigned into 6 groups:normal control,model,high-,medium-,and low-dose Gegen Qinliantang(2.5,5,10 g·kg^(-1)),and pioglitazone(3.125 mg·kg^(-1)).The rats were administrated with corresponding drugs by gavage for 6 weeks,and the normal control group and model group were administrated with the same amount of normal saline.During the experiment period,the changes of body weight were recorded,and the FBG,FINS,HOMA-IR,TG,and TC were determined at the end of the experiment.Hematoxylin-eosin(HE)staining was employed to observe the pathological changes of skeletal muscle in rats.The levels of reactive oxygen species(ROS)and malondialdehyde(MDA)in the skeletal muscle were measured strictly according to the manuals of the reagent kits.Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was performed to measure the mRNA levels of silencing information regulator 1(SIRT1),peroxisome proliferator-activated receptor-gamma coactivator1α(PGC1α),and nuclear respiratory factor 1(Nrf1)in the skeletal muscle.Western blot and immunohistochemistry were employed to assess the expression of SIRT1,PGC1α,and Nrf1 in the skeletal muscle.Result:Compared with the normal control group,the model g

关 键 词：葛根芩连汤 追赶生长 胰岛素抵抗 糖脂代谢 沉默信息调节因子1(SIRT1)/过氧化物酶体增殖物激活受体γ共激活剂-1α(PGC1α)/核因子E_(2)相关因子1(Nrf1)信号通路 

分 类 号：R2-0[医药卫生—中医学] R33[生物学—生理学] R289Q493.5R589