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 reduced. Conclusion: Liraglutide can reduce myocardial ischemia-reperfusion injury in DM rats, the mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.
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