糖痹康颗粒对2型糖尿病合并非酒精性脂肪肝大鼠PI3K通路的影响  

Effect of Tangbikang Granules on PI3K Pathway in Type 2 Diabetic Mellitus Rats with Non-alcoholic Fatty Liver Disease

作　　者：张亚奇 秦灵灵 张程斐[4] 张秋娥 白惠中 刘港 左心玮 赵毅 刘铜华 穆晓红[1] ZHANG Yaqi;QIN Lingling;ZHANG Chengfei;ZHANG Qiue;BAI Huizhong;LIU Gang;ZUO Xinwei;ZHAO Yi;LIU Tonghua;MU Xiaohong(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Science and Technology Office,Beijing University of Chinese Medicine,Beijing 100029,China;Disciplinary Innovation Base of the Ministry of Education,Beijing 100029,China;School of Life Sciences,Beijing University of Chinese Medicine,Beijing 100029,China;School of Traditional Chinese Medicine(TCM),Beijing University of Chinese Medicine,Beijing 100029,China;Key Laboratory of TCM Health Sciences,Ministry of Education,Beijing University of Chinese Medicine,Beijing 100029,China;International Joint Research Center for Diabetes Prevention and Treatment with TCM,Ministry of Science and Technology,Beijing 100029,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学科技处,北京100029 [3]教育部高等学校学科创新引智基地,北京100029 [4]北京中医药大学生命科学学院,北京100029 [5]北京中医药大学中医学院,北京100029 [6]北京中医药大学教育部中医养生学重点实验室,北京100029 [7]科技部中医药防治糖尿病国际联合研究中心,北京100029

出　　处：《中国实验方剂学杂志》2023年第9期71-80,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81874467);北京市自然科学基金项目(L192059)。

摘　　要：目的:探讨糖痹康颗粒对2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)的治疗及阐明作用机制。方法:采用自发性的雄性Zucker糖尿病脂肪(ZDF)大鼠,建立T2DM合并NAFLD模型。造模成功的大鼠进行糖痹康颗粒高、中、低剂量组(2.5、1.25、0.625 g·kg^(-1))持续灌胃治疗12周。治疗期间每4周记录空腹血糖(FBG)和体质量变化。取材前1周,检测给药治疗对大鼠进食量影响;并进行夜间禁食12 h后进行口服葡萄糖耐量实验(OGTT),曲线下面积(AUC)评价糖耐量,计算胰岛素抵抗指数(HOMA-IR)。腹主动脉取血和取肝脏,测定血糖和血脂代谢指标,包括空腹血清胰岛素(FINS)、血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及游离脂肪酸(NEFA)。对肝脏进行称质量计算肝脏指数,并对其进行肝脏组织形态学苏木素-伊红(HE)染色、过碘酸-Schiff(PAS)染色观察分析。蛋白免疫印迹法(Western blot)检测胰岛素受体底物(IRS)、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)和磷酸化IRS、Akt蛋白的表达水平。所有数据采用SPSS 20.0软件进行分析。结果:与正常组比较,模型组大鼠摄食量显著增多(P<0.01);与模型组比较,其余各给药组糖尿病大鼠摄食量减少(P<0.05,P<0.01)。与正常组比较,模型组大鼠8、12周体质量显著降低(P<0.01)。与模型组比较,糖痹康颗粒组在一定程度上降低FBG水平,且呈浓度依赖性。与正常组比较,模型组OGTT血糖值和AUC显著增高(P<0.01);与模型组比较,糖痹康颗粒各组和二甲双胍组OGTT血糖值整体降低,AUC差异有统计学意义(P<0.01)。与正常组比较,模型组大鼠血清FINS、HOMA-IR指数均显著升高(P<0.01);与模型组比较,糖痹康颗粒各组大鼠血清FINS水平、HOMAIR指数均显著降低(P<0.01)。与正常组比较,模型组大鼠血清TG、TC、HDL-C及NEFA水平均明显升高(P<0.05,P<0.01),LDL-C水平呈升高趋势,但差异无统�Objective:This study aims to investigate the therapeutic effect of Tangbikang granules(TBK)on type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)and to elucidate the underlying mechanism.Method:T2DM and NAFLD were induced in ZDF rats,which were then respectively treated(ig)with low-dose(0.625 g·kg^(-1)),medium-dose(1.25 g·kg^(-1)),and high-dose(2.5 g·kg^(-1))TBK for 12 weeks.Fasting blood glucose(FBG)and body mass were recorded every 4 weeks during the treatment.One week before sampling,the feed intake of rats was detected,and after 12 h night fasting,oral glucose tolerance test(OGTT)was performed.The area under the curve(AUC)was used to evaluate glucose tolerance,and the homeostatic model assessment for insulin resistance(HOMA-IR)was calculated.Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes:Fasting serum insulin(FINS),serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),and nonesterified fatty acids(NEFA).The liver was weighed to calculate the liver index,and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.The protein levels of insulin receptor substrate(IRS),phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)and phosphorylated IRS and Akt were detected by Western blotting.All data were analyzed by SPSS 20.0.Result:The feed intake of the model group was higher than that in the normal group(P<0.01),and the feed intake the administration groups was lower than that in the model group(P<0.05,P<0.01).At the 8th and 12th week,the body mass in the model group was lower than that in the normal group(P<0.01).Compared with the model group,TBK reduced FBG in a concentration-dependent manner.The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group(P<0.01).The blood glucose value in OGTT was decreased in

关 键 词：糖痹康颗粒 2型糖尿病 非酒精性脂肪肝 胰岛素受体底物-1 磷脂酰肌醇3-激酶通路 分子机制 

分 类 号：R2-0[医药卫生—中医学] R22R242R2-031R285.5