利拉鲁肽通过激活Nrf2/HO-1信号通路对糖尿病大鼠心肌损伤的影响  

Effect of liraglutide on myocardial injury in diabetic ratsthrough activation of Nrf2/HO-1 signaling pathway

作　　者：高媛[1] 王宇亮 王少兰 GAO Yuan;WANG Yu-liang;WANG Shao-lan(Dept of Cardiology,the First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou Inner Mongolia 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心内科,内蒙古包头014010

出　　处：《中国药理学通报》2025年第3期538-543,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81940038);内蒙古自治区自然科学基金资助项目(No 2021LHMS08008);包头医学院科学研究基金项目(No BYJJ-QWB202227)。

摘　　要：目的探究利拉鲁肽通过激活Nrf2/HO-1信号通路对糖尿病大鼠心肌损伤的影响。方法将40只大鼠分为正常组、糖尿病模型组、二甲双胍组、利拉鲁肽组,建模后正常组与模型组不干预,二甲双胍组灌胃二甲双胍250 g·kg^(-1),利拉鲁肽组注射0.324 g·kg^(-1)利拉鲁肽,均每天1次,共1个月。采用ELISA法检测血糖、胰岛素水平;HE染色观察病理学变化;免疫印迹及荧光定量PCR分别检测Nrf2、HO-1、NLRP3、IL-1β、caspase-1表达。结果与模型组比较,各治疗组空腹血糖、NLRP3、caspase-1、IL-1β降低,胰岛素、Nrf2、HO-1升高(P<0.05),其中利拉鲁肽组效果更明显。结论利拉鲁肽对糖尿病心肌具有保护作用,其机制可能与调节Nrf2/HO-1信号通路、改善细胞焦亡等因素相关。Aim To explore the effect of liraglutide on myocardial injury in diabetic rats by activating Nrf2/HO-1 signaling pathway.Methods Forty rats were divided into thenormal group,model group,metformin group and liraglutide group.After modeling,the normal group and model group did not intervene,the metformin group was administrated with 250 g·kg^(-1) metformin,and the liraglutide group was injected with 0.324 g·kg^(-1) liraglutide,once a day for a total of one month.Blood sugar and insulin levels were detected by ELISA,and the pathological changes were observed by HE staining.The expression of Nrf2,HO-1,NLRP3,IL-1βand caspase-1 were detected by Western blot and fluorescent quantitative PCR,respectively.Results Compared with the model group,the fasting glucose,NLRP3,caspase-1,IL-1βof the treatment group were reduced,while insulin,Nrf2,HO-1 levels increased(P<0.05),of which the effects of liraglutide group was more obvious.Conclusions Liraglutide has a protective effect on diabetic myocardium,and its mechanism may be related to the regulation of Nrf2/HO-1 signaling pathway and the improvement of pyroptosis.

关 键 词：糖尿病 利拉鲁肽 NRF2 HO-1 细胞焦亡 心肌损伤 

分 类 号：R-332[医药卫生] R329.24R329.411R587.1R977.6