衢枳壳提取物改善2型糖尿病小鼠胰岛素抵抗的作用研究  

Effect of Quzhou Aurantii Fructus Extract on Insulin Resistance in Type 2 Diabetic Mice

作　　者：汪雯[1] 蓝天 郑芳[2] 汪丽霞 张峰 王思为 WANG Wen;LAN Tian;ZHENG Fang(Preventive Treatment Center,Zhejiang Chinese Medical University Affiliated Four-provinces Marginal Hospital of Traditional Chinese Medicine,Quzhou Hospital of Traditional Chinese Medicine,Quzhou 324000,China;The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People's Hospital)

机构地区：[1]浙江中医药大学附属四省边际中医院,衢州市中医医院治未病中心,浙江衢州324000 [2]温州医科大学附属衢州医院,衢州市人民医院 [3]衢州市常山县农业农村局

出　　处：《浙江中医药大学学报》2022年第9期936-944,共9页Journal of Zhejiang Chinese Medical University

基　　金：国家自然科学基金项目(81903873);衢州市科技计划竞争性分配项目(2019K34);浙江省医药卫生科技计划项目(2020PY087)。

摘　　要：[目的]研究衢枳壳(Quzhou Aurantii Fructus,QAF)提取物改善2型糖尿病(type 2 diabetes mellitus,T2DM)小鼠胰岛素抵抗的作用及其具体机制。[方法]以6只雄性db/m小鼠为对照组(以蒸馏水灌胃),选取同性别T2DM db/db小鼠24只,随机均分至模型组(以蒸馏水灌胃)、二甲双胍组(以200 mg·kg^(-1)二甲双胍灌胃)、QAF低剂量组(以100 mg·kg^(-1)QAF提取物灌胃)、QAF高剂量组(以300 mg·kg^(-1)QAF提取物灌胃)。连续灌胃10周,监测小鼠体质量、肝质量、附睾脂肪质量;检测空腹血糖(fasting blood glucose,FBG)、空腹血清胰岛素(fasting serum insulin,FINS)水平,以此计算胰岛素敏感指数(insulin sensitivity index,ISI)、胰岛素抵抗指数(insulin resistance index,HOMA-IR);检测血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、游离脂肪酸(non-esterified fatty acid,NEFA)水平;检测肝组织超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、还原型谷胱甘肽(reduced glutathione,GSH)活性,检测肝脏TC、TG表达;苏木精-伊红(hematoxylin-eosin,HE)染色观察肝组织病理结构变化;实时荧光定量聚合酶链式反应(Real-time fluorescence quantitative polymerase chain reaction,Real-time qPCR)检测肝脏中脂肪合成基因固醇调节元件结合转录因子1(sterol regulatory element-binding transcription factor 1,Srebf1)、脂肪酸合酶(fatty acid synthase,Fasn)、硬酯酰辅酶A去饱和酶(stearyl-CoA desaturase 1,Scd1)、乙酰辅酶A羧化酶1(acetyl-CoA carboxylase 1,Acc1)表达;免疫印迹法检测腺苷酸活化蛋白激酶(adenosine monophosphate activated protein kinase,AMPK)、磷酸化腺苷酸活化蛋白激酶(phosphorylated adenosine monophosphate activated protein kinase,p-AMPK)、固醇调节元件结合蛋白-1(sterol regulatory element binding protein-1,SREBP-1)蛋白表达。[结果]与模型组比较,不同剂量QAF提取物灌胃干预后,T2DM小鼠的肝质量明显下降(P<0.05,P<0.01),但体质量和附睾脂�[Objective] To investigate the effects of Quzhou Aurantii Fructus(QAF) extract on improving insulin resistance(IR) in type 2diabetes mellitus(T2DM) mice and its underlying mechanism. [Methods] Six male db/m mice were applied as control group(intragastric administration of distilled water), and twenty-four T2DM db/db mice of the same sex were selected. They were randomly and equally divided into model group(intragastric administration of distilled water), metformin group(intragastric administration of 200 mg·kgmetformin), low-dose QAF group(intragastric administration of 100 mg·kgQAF extract) and high-dose QAF group(intragastric adminis tration of 300 mg·kgQAF extract). After 10 weeks of intragastric administration, the body weight of mice and the weight of liver and epididymal fat were recorded;fasting blood glucose(FBG) and fasting serum insulin(FINS) were detected to calculate insulin sensitivity index(ISI) and insulin resistance index(HOMA-IR);the serum total cholesterol(TC), triglyceride(TG) and non-esterified fatty acid(NEFA) were detected;the activities of hepatic superoxide dismutase(SOD), catalase(CAT), reduced glutathione(GSH) were observed and TC, TG levels in the liver tissue were detected;hematoxylin-eosin(HE) staining was utilized to observe the hepatic histopathological changes of mice;Real-time fluorescence quantitative polymerase chain reaction(Real-time qPCR) was applied to detect the mRNA expressions of fat synthesis genes sterol regulatory element-binding transcription factor 1(Srebf1), fatty acid synthase(Fasn), stearyl-CoA desaturase 1(Scd1), and acetyl-CoA carboxylase 1(Acc1);Western blot was used to detect the protein expressions of adenosine monophosphate activated protein kinase(AMPK), phosphorylated adenosine monophosphate activated protein kinase(p-AMPK) and sterol regulatory element binding protein-1(SREBP-1). [Results] Compared with model group, the liver weight of T2DM mice decreased significantly after gavage with different doses of QAF extract(P<0.05, P<0.01), but the body weigh

关 键 词：衢枳壳 2型糖尿病 胰岛素抵抗 肝脏 脂质合成 血脂代谢 AMPK SREBP-1 

分 类 号：R331[医药卫生—人体生理学]