摘要
目的研究利拉鲁肽对链脲霉素(STZ)致糖尿病大鼠心肌损伤的保护作用机制。方法大鼠腹腔注射STZ构建糖尿病大鼠模型,腹腔注射利拉鲁肽50和200μg·kg^-1干预,检测大鼠空腹血糖(FPG)、空腹胰岛素(FINS)和血脂指标情况,应用光、电镜及免疫组化观察心肌组织,并取心肌组织作mRNA及蛋白检测。结果与正常组比较,模型组大鼠的心肌肥厚指数(HWI)、FPG、FINS、总胆固醇(TC)和三酰甘油(TG)水平显著升高,而利拉鲁肽干预后上述指标均显著降低(P<0.05);模型组大鼠心肌细胞及间质胶原纤维排列松散,自噬小体数量显著减少,利拉鲁肽干预后心肌纤维化程度显著降低,自噬小体数量显著升高(P<0.05);模型组大鼠心肌组织中自噬标志因子(LC3B)和腺苷酸活化蛋白激酶(AMPK)磷酸化水平均降低,转化生长因子-β1(TGF-β1)和Ⅰ型胶原蛋白(Col-1)的mRNA表达水平以及选择性自噬接头蛋白(p62)、哺乳动物雷帕霉素靶蛋白(mTOR)磷酸化水平均显著升高,利拉鲁肽干预后LC3B和AMPK磷酸化水平均升高,TGF-β1、Col-1的mRNA表达水平以及p62、mTOR磷酸化水平均显著降低(P<0.05)。结论利拉鲁肽能通过抑制促纤维化因子表达从而抑制心肌组织纤维化,同时促进AMPK/mTOR介导的自噬来改善糖尿病引起的心肌损伤。
Objective To study the protective effect mechanism of liraglutide on streptozotocin(STZ)induced myocardial injury in diabetes mellitus(DM)rats.Methods The intraperitoneal injection of STZ was conducted to prepare DM model.The 50 and 200μg·kg^-1 liraglutide were intraperitoneally injected for intervention.The fasting blood glucose(FPG),fasting insulin(FINS)and blood lipid indexes were detected.The myocardial tissues were observed by light,electron microscopy and immunohistochemistry.The myocardial tissues were applied in mRNA and protein tests.Results Compared with normal group,the cardiac hypertrophy index(HWI),levels of FPG,FINS,total cholesterol(TC)and triglyceride(TG)of model group were significantly increased,after liraglutide intervention,the above indexes were significantly decreased(P<0.05);the arrangement of myocardial cells and interstitial collagen fibers was loose in model group,number of autophagosomes was significantly reduced,after liraglutide intervention,degree of myocardial fibrosis was significantly decreased,while the numbers of autophagosomes was significantly increased(P<0.05).The levels of autophagy marker factor(LC3B)in myocardial tissue and phosphorylation of adenosine monophosphate activated protein kinase(AMPK)were decreased in model group,while the relative expression levels of transforming growth factor-β1(TGF-β1)and typeⅠcollagen(Col-1)mRNA,phosphorylation levels of selective autophagy adaptor protein(p62)and mammalian target of rapamycin(mTOR)were significantly increased,After liraglutide intervention,phosphorylation levels of LC3B and AMPK were increased,while the relative expression levels of TGF-β1 and Col-1 mRNA,phosphorylation levels of p62 and mTOR were significantly decreased(P<0.05).Conclusion Liraglutide inhibits myocardial fibrosis by inhibiting the expression of pro-fibrotic factors,and promotes AMPK/mTOR mediated autophagy to improve myocardial damage caused by DM.
作者
费龙
马浩然
毛晓丽
文煜
FEI Long;MA Haoran;MAO Xiaoli;WEN Yu(Department of Pharmacy,the First Hospital of Wuhan,Wuhan 430022,China;Medical Center of Wuhan Conservatory of Music,Wuhan 430000,China)
出处
《西北药学杂志》
CAS
2021年第1期46-51,共6页
Northwest Pharmaceutical Journal
基金
国家自然科学基金项目(编号:81803839)。
关键词
利拉鲁肽
糖尿病
心肌损伤
腺苷酸活化蛋白激酶
liraglutide
diabetes mellitus
myocardial injury
adenosine monophosphate activated protein kinase(AMPK)
