利拉鲁肽对2型糖尿病合并非酒精性脂肪肝模型大鼠的肝保护作用  

Protective effect of liraglutide on liver of model rats with type 2 diabetes and non-alcoholic fatty liver disease

作　　者：蔡辉耀[1] 杨鑫娜[1] 陈丽君 林家煜[1] 梁波[1] 李良毅[1] CAI Hui-yao;YANG Xin-na;CHEN Li-jun;LIN Jia-yu;LIANG Bo;LI Liang-yi(Department of Endocrinology and Metabolism,Second Affiliated Hospital of Fujian Medical University,Quanzhou 362000,Fujian Province,China)

机构地区：[1]福建医科大学附属第二医院内分泌与代谢科,福建泉州362000

出　　处：《中国临床药理学杂志》2020年第22期3739-3742,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的观察利拉鲁肽对2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)模型大鼠的肝保护作用及对小分子G蛋白(Rho)/Rho激酶(Rock)信号通路的影响。方法采用高糖高脂饲料喂养4周联合一次性腹腔注射链脲佐菌素(STZ)的方法诱导建立T2DM合并NAFLD大鼠模型,将成功制备的模型大鼠随机分为模型组(n=30)与实验组(n=30),另选取30只大鼠仅予以基础饲料喂养,不腹腔注射STZ作为对照组。实验组腹腔注射利拉鲁肽600μg·kg-1·d-1,模型组和对照组腹腔注射等量生理盐水,连续干预4周。用全自动生物化分析仪检测大鼠空腹血糖(FBG)与血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)水平;用放射免疫法检测空腹胰岛素(FINS)水平;用苏木精-伊红(HE)染色观察肝组织病理学变化;用蛋白质印迹(Wb)法检测肝组织小分子G蛋白A(RhoA)、Rho激酶1(Rock1)与Rock2蛋白表达。结果对照组、模型组与实验组大鼠FBG水平分别为(5.06±1.13),(36.21±1.04),(17.96±0.61)mmol·L^-1;GPT水平分别为(27.83±3.24),(351.26±6.49),(73.11±10.43)U·L^-1;GOT水平分别为(65.83±6.21),(405.32±11.37),(86.54±17.02)U·L^-1。与对照组比较,模型组大鼠FBG、血清GPT、GOT、FINS水平与胰岛素抵抗指数(HOMA-IR)、胰岛素敏感性指数(ISI)及肝组织RhoA、Rock1、Rock2蛋白相对表达量均显著升高,且实验组低于模型组(均P<0.05)。结论利拉鲁肽可显著降低T2DM合并NAFLD模型大鼠的血糖,改善血清生化指标水平与胰岛素敏感性,从而发挥肝保护作用,其作用机制可能与抑制肝组织Rho/Rock通路的信号转导相关。Objective To investigate the liver protection effect of liraglutide on type 2 diabetes(T2DM) combined with non-alcoholic fatty liver disease(NAFLD) model rats and the effect on Ras homologous(Rho)/Rho kinase(Rock) signaling pathway. Methods Feeding high-sugar and high-fat diet for 4 weeks combined with one-time intraperitoneal injection of streptozotocin(STZ) to induce the establishment of T2DM combined with NAFLD rat models, the successfully prepared model rats were randomly divided into model group(n=30) and test group(n=30), and 30 rats were selected to be fed only with basic feed, and STZ was not injected as control group. Rats in test group were intraperitoneally injected with liraglutide(600μg·kg-1·d-1),model group and control group were intraperitoneally injected with the same amount of normal saline for 4 weeks. The levels of fasting blood glucose(FBG),serum glutamic-pyruvic transaminase(GPT) and glutamic-oxaloacetic transaminase(GOT) levels were measured by automatic biochemical analyzer;the levels of serum fasting insulin(FINS) were detected by radioimmunoassay;hematoxylin-eosin(HE) staining was used to observe the pathological changes of liver tissues;Western blotting(Wb) method was used to detect the expression of ras homologous A(RhoA),Rho kinase 1(Rock1) and Rock2 protein in liver tissues. Results The FBG levels in control group,model group and test group were(5. 06 ± 1. 13),(36. 21 ± 1. 04),(17. 96 ± 0. 61) mmol·L^-1;GPT levels were(27. 83 ± 3. 24),(351. 26 ± 6. 49),(73. 11 ± 10. 43) U·L^-1;GOT levels were(65. 83 ± 6. 21),(405. 32 ± 11. 37),(86. 54 ± 17. 02) U·L^-1. Compared with control group,the levels of FBG,serum GPT,GOT,FINS and Homeostasis model assessment-insulin resistance(HOMA-IR),insulin sensitivity index and the relative expression of RhoA,Rock1,Rock2 protein in liver tissues of model group were significantly increased,and test group was lower than model group(all P < 0. 05). Conclusion Liraglutide could reduce the blood glucose of T2DM combined with NAFLD model rats,impro

关 键 词：2型糖尿病 非酒精性脂肪肝 利拉鲁肽 小分子G蛋白A RHO激酶 

分 类 号：R977.15[医药卫生—药品]