利拉鲁肽通过激活Nrf2/HO-1信号通路改善糖尿病大鼠心肌缺血再灌注损伤  

Liraglutide improves myocardial ischemia-reperfusion injury in diabetic rats by activating Nrf2/HO-1 signaling pathway

作　　者：杨浩[1] 孙淑艳[1] YANG Hao;SUN Shuyan(The First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014010,China)

机构地区：[1]内蒙古科技大学包头医学院第一附属医院,内蒙古包头014010

出　　处：《包头医学院学报》2025年第2期6-12,共7页Journal of Baotou Medical College

基　　金：内蒙古自治区自然科学基金项目(2021LHMS08008)。

摘　　要：目的:通过建立糖尿病(diabetes mellitus,DM)大鼠缺血再灌注模型,观察利拉鲁肽对心肌缺血再灌注损伤(myocardial ischemia/reperfusion injury,MIRI)后心肌梗死面积、心肌氧化抗氧化物质水平、各组心肌组织抗氧化应激通路关键蛋白核因子E2相关因子2(nuclear factor E2-related factor 2,Nrf2)、血红素加氧酶-1(heme oxygenase-1,HO-1)的表达水平的影响,探讨利拉鲁肽对DM大鼠MIRI的影响及可能机制。方法:将雄性SD大鼠随机分为正常组、I/R组、利拉鲁肽+I/R组、利拉鲁肽+I/R+Nrf2抑制剂组(Nrf2抑制剂组)、利拉鲁肽+I/R+HO-1抑制剂组(HO-1抑制剂组)、利拉鲁肽+I/R+Nrf2抑制剂+HO-1抑制剂组(双抑制剂组)。构建DM及缺血再灌注模型,酶联免疫吸附试验(ELISA)检测丙二醛(malondialdehyde,MDA)含量及超氧化物酶(superoxide dismutase,SOD)含量;苏木素-伊红(HE)染色观察大鼠心肌组织形态;Western印迹法检测大鼠心肌组织中Nrf2/HO-1通路相关蛋白表达。结果:与正常组相比,I/R组的MDA含量显著升高,SOD含量显著降低;与I/R组相比,利拉鲁肽+I/R组的心肌梗死面积减少;与I/R组相比,利拉鲁肽+I/R组心肌组织细胞排列较为整齐,肌丝轮廓清晰,且细胞间隙紧密、均匀;与正常组相比,I/R组心肌组织中Nrf2、HO-1蛋白水平显著降低,心肌组织出现明显的病理损伤,与I/R组相比,利拉鲁肽+I/R组的大鼠血清MDA含量显著降低,SOD含量升高,心肌组织中Nrf2、HO-1蛋白水平显著升高,心肌组织病理损伤减轻。结论:利拉鲁肽可减轻DM大鼠心肌缺血再灌注损伤,其作用机制可能与激活Nrf2/HO-1信号通路有关。Objective:To observe the effects of liraglutide on myocardial infarction area,myocardial oxidative and antioxidant levels,and the expression levels of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in myocardial tissue after myocardial ischemia/reperfusion injury(MIRI)by establishing an ischemia-reperfusion model of diabetes mellitus(DM)rats,and to explore the effect of liraglutide on MIRI in DM rats and its possible mechanism.Methods:Male SD rats were randomly divided into normal group,I/R group,liraglutide+I/R group,liraglutide+I/R+Nrf2 inhibitor group(Nrf2 inhibitor group),liraglutide+I/R+HO-1 inhibitor group(HO-1 inhibitor group),liraglutide+I/R+Nrf2 inhibitor+HO-1 inhibitor group(double inhibitor group).DM and ischemia-reperfusion models were constructed.Enzyme-linked immunosorbent assay(ELISA)was used to detect malondialdehyde(MDA)content and superoxide dismutase(SOD)content.The morphology of rat myocardial tissue was observed by hematoxylin-eosin(HE)staining.Western blotting was used to detect the expression of Nrf2/HO-1 pathway-related proteins in rat myocardial tissue.Results:Compared with the normal group,the MDA content in the I/R group was significantly increased,and the SOD content was significantly decreased.Compared with the I/R group,the myocardial infarction area of the liraglutide+I/R group was reduced.Compared with the I/R group,the myocardial tissue cells in the liraglutide+I/R group were arranged neatly,the myofilament contour was clear,and the intercellular space was tight and uniform.Compared with the normal group,the levels of Nrf2 and HO-1 protein in the myocardial tissue of the I/R group were significantly reduced,and the myocardial tissue showed obvious pathological damage.Compared with the I/R group,the serum MDA content of the rats in the liraglutide+I/R group was significantly reduced,the SOD content was increased,the levels of Nrf2 and HO-1 protein in the myocardial tissue were significantly increased,and the pathological damage of the myocardial tissue was reduce

关 键 词：利拉鲁肽 核因子E2相关因子2/血红素加氧酶-1 心肌缺血再灌注 氧化应激损伤 

分 类 号：R28[医药卫生—中药学]