基于AMPK/GLUT4/GSK3β/PPARα信号通路研究地骨皮水提物改善2型糖尿病大鼠胰岛素抵抗的实验研究  

Experimental study on the improvement of insulin resistance in rats with type 2 diabetes mellitus with Cortex Lycii Radicis based on AMPK/GLUT4/GSK3β/PPARα signaling pathway

作　　者：姚欢欢[1] 陈吉[1] 陈思思 周迪夷 YAO Huanhuan;CHEN Ji;CHEN Sisi;ZHOU Diyi(Department of Pharmacy,Huzhou Third People′s Hospital,Zhejiang Province,Huzhou 313002,China;Department of Endocrinology,Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine,Zhejiang Province,Hangzhou 310003,China)

机构地区：[1]浙江省湖州市第三人民医院药剂科,浙江湖州313002 [2]浙江省中西医结合医院内分泌科,浙江杭州310003

出　　处：《中国医药导报》2020年第5期8-12,F0004,共6页China Medical Herald

基　　金：国家自然科学基金资助项目（81703996）

摘　　要：目的基于AMPK/GLUT4/GSK3β/PPARα信号通路探讨地骨皮对2型糖尿病(T2DM)大鼠胰岛素抵抗(IR)的影响。方法60只6周龄Wistar大鼠按随机数字表法分为对照组(n=10)和高脂实验组(n=50),采用随机数字表法将高脂实验组中造模成功且符合模型要求的40只大鼠分为模型组,阳性对照组[罗格列酮2 mg/(kg·d)],地骨皮低剂量组[5 mg/(kg·d)]、高剂量组[10 mg/(kg·d)],每组10只。连续给药6周后,比较各组大鼠空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平,并观察肝脏形态。BCA法测定肝脏中蛋白质质量浓度。结果模型组大鼠FBG高于对照组,地骨皮低、高剂量组FBG含量均显著低于模型组,差异有统计学意义(均P<0.05)。模型组TC、TG、LDL-C水平高于对照组,HDL-C水平低于对照组,差异均有统计学意义(均P<0.05);干预6周后,地骨皮低、高剂量组TC、TG、LDL-C水平低于模型组,HDL-C水平高于模型组,差异均有统计学意义(均P<0.05)。模型组ALT、AST水平高于对照组,干预6周后,地骨皮低、高剂量组ALT、AST水平低于模型组,差异均有统计学意义(均P<0.05)。苏木精-伊红染色显示:对照组肝小叶结构清晰;模型组肝细胞排列紊乱,脂质空泡明显可见;地骨皮高剂量组大鼠的肝脂肪空泡明显减少,肝细胞结构病变和脂肪变性程度显著改善。油红O染色显示:模型组大鼠的肝脏有明显累积的脂质液滴,地骨皮高剂量组脂质累积减少。模型组大鼠肝脏中p-AMPK、PPARα和GLUT4的水平低于对照组,GSK3β水平高于对照组,差异均有统计学意义(均P<0.05);地骨皮高剂量组p-AMPK、PPARα和GLUT4蛋白水平上调显著,GSK3β水平显著下调(P<0.05)。结论地骨皮可显著降低T2DM大鼠的FBG,改善血脂异常和肝脏病理变化,其可能通过AMPK信号通路途径上调GLUT4和PPARα�Objective To study on the improvement of insulin resistance(IR)in rats with type 2 diabetes mellitus(T2DM)was conducted based on AMPK/GLUT4/GSK3β/PPARαsignaling pathway.Methods Sixty Wistar rats were divided into control group and high-fat experimental group(n=50),and 40 rats which were successfully modeled and met the requirements of the model in the high-fat experimental group were divided into,model group,positive control group[Rosiglitazone 2 mg/(kg·d)],Cortex Lycii Radicis low dose group[5 mg/(kg·d)]and high dose group[10 mg/(kg·d)]by the random number table method,with 10 rats in each group.Each groups were given continuous administration for 6 weeks.Fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aminotransferase(AST)and alanine aminotransferase(ALT)levels of rats in each group were compared and liver morphology was observed.Protein mass concentration in liver was determined by BCA method.Results FBG levels in model group were higher than those in control group,while FBG levels in Cortex Lycii Radicis low dose group and Cortex Lycii Radicis high dose group were significantly lower than those in model group,with statistically significant differences(all P<0.05).The levels of TC,TG and LDL-C in model group were higher than those in control group,while the levels of HDL-C were lower than those in control group,with statistically significant differences(all P<0.05).After 6 weeks of intervention,the levels of TC,TG and LDL-C in Cortex Lycii Radicis low dose group and Cortex Lycii Radicis high dose group were lower than those in model group,while the levels of HDL-C were higher than those in model group,with statistically significant differences(all P<0.05).The levels of ALT and AST in model group were higher than those in control group.After 6 weeks of intervention,the levels of ALT and AST in Cortex Lycii Radicis low dose group and Cortex Lycii Radicis high dose group were lower than those in model gro

关 键 词：地骨皮 2型糖尿病模型大鼠 胰岛素抵抗 磷酸腺苷活化蛋白激酶 

分 类 号：R285[医药卫生—中药学]