鸢尾素有效降低阿霉素诱导心肌损伤大鼠炎症反应和心肌细胞凋亡

Irisin efficiently decreases the inflammatory responses and cardiomyocyte apoptosis in adriamycin-induced myocardial injury rat

目的研究鸢尾素(Irisin)对阿霉素诱导心肌损伤大鼠的炎症反应和心肌细胞凋亡的影响及其作用机制。方法采用阿霉素诱导方法建立Sprague-Dawley(SD)大鼠心肌损伤模型并随机分成正常对照组(control group)、心肌损伤模型组(model group)和低、中、高浓度鸢尾素处理组。Irisin处理4周后,检测各组大鼠心功能指标(HR、LVSP、LVEDP、+dp/dtmax、-dp/dtmax),HE染色检测心肌组织病理变化,流式细胞术检测心肌组织中活性氧(ROS)水平;ELISA方法检测心肌组织中炎症因子(IL-6、IL-10、TNF-α、IFN-γ)水平;Tunel染色检测心肌组织细胞凋亡情况;免疫印迹法检测心肌组织中p-AKT/AKT水平变化。结果模型组大鼠心功能指标显著下降,且心肌组织病理损伤严重;心肌组织中ROS阳性比例、炎症因子水平和细胞凋亡率均显著上升,而p-AKT/AKT水平显著下降(P<0.05)。经低、中、高浓度Irisin作用后,各组大鼠心功能指标逐渐回升,心肌组织病理损伤也逐渐减轻,且心肌组织中ROS阳性比例、炎症因子水平和细胞凋亡率均逐渐降低,而p-AKT/AKT水平显著上升(P<0.05)。结论Irisin有效降低阿霉素诱导的心肌损伤,通过抑制炎症反应、ROS水平和心肌细胞凋亡发挥作用并与AKT磷酸化相关。

This study was designed to investigate the effects of irisin on inflammatory response and cardiomyocyte apoptosis in adriamycin induced myocardial injury rats and its mechanism.The myocardial injury model of Sprague Dawley(SD)rats was established by adriamycin induction,and divided into model group and irisin low-,medium-,high-dose groups,with untreated rate as control group.After Irisin treatment for 4 weeks,the indexes of cardiac function(HR,LVSP,LVEDP,+dp/dtmax,-dp/dtmax)were detected;the pathological changes of myocardial tissue were detected by HE staining;and the level of reactive oxygen species(ROS)in myocardial tissue were detected by flow cytometry.The inflammatory factors(IL-6,IL-10,TNF-α,IFN-γ)in myocardial tissue were detected by ELISA;the cardiomyocyte apoptosis was detected by TUNEL staining;and the level of p-AKT/AKT in myocardial tissue were detected by Western blotting.Data showed that the cardiac function indexes of model group were decreased significantly,the pathological injury of myocardial tissue was serious,the positive proportion of ROS,the level of inflammatory factors and the apoptosis rate were increased significantly,while the level of p-AKT/AKT was decreased significantly(all P<0.05).Under the action of low,medium and high concentrations of irisin,the cardiac function indexes of rats in each group were gradually increased,and the pathological injury of myocardial tissue were gradually decreased,the positive proportion of ROS,the level of inflammatory factors and the apoptosis rate were decreased gradually,while the level of p-AKT/AKT were increased significantly(all P<0.05).In conclusion,irisin can effectively reduce adriamycin-induced myocardial injury by down-regulating inflammatory reaction,ROS level and cardiomyocyte apoptosis,and is related to Akt phosphorylation.