摘要
目的 研究二参汤对冠心病模型大鼠心肌细胞铁死亡的影响.方法 将60只SPF级SD大鼠随机分为空白对照组(Ctrl组)、模型组(Model组)、二参汤高剂量组(ESH组)、二参汤中剂量组(ESM组)、二参汤低剂量组(ESL组)、阳性药组(Y组).应用维生素D3 联合垂体后叶素配合高脂饲料连续喂养12周,构建冠心病大鼠模型,采集Ⅱ导联常规心电图;HE、Masson染色法观察各组大鼠心肌组织病理形态学变化;ELISA检测各组大鼠心肌组织中ROS、LPO、SOD、MDA、4-HNE、GSH和Fe2+水平;RT-PCR检测大鼠心肌组织中铁死亡相关基因FTH1、SLC7A11、GPX4 mRNA表达水平.结果 二参汤可改善心肌组织中胶原纤维增生,减轻炎症细胞浸润;增加GSH、SOD活性(P<0.05),降低ROS、LPO、MDA和4-HNE含量(P<0.05),降低Fe2+水平(P<0.01);促进FTH1、GPX4、和SLC7A11 mRNA表达(P<0.05).结论 二参汤能够减轻冠心病大鼠心肌组织损伤,其机制可能与抑制心肌细胞铁死亡有关.
Abstract
Objective To study the effect of Ershen Tang on ferroptosis of cardiomyocytes in rats modelled with coronary heart disease.Methods A rat model of coronary heart disease was constructed by applying vitamin D3 combined with posterior pituitary hormone with high-fat feed for 12 consecutive weeks;rats with successful modelling were randomly divided into a blank control group(Ctrl),a model group(Model),an Ershen Tang high-dose group(ESH),an Ershen Tang medium-dose group(ESM),an Ershen Tang low-dose group(ESL),and a positive drug group(Y).Conventional electrocardiogram was performed in Ⅱ leads;pathological and morphological changes of myocardial tissues of rats in each group were observed by HE and Masson staining;ELISA detected the levels of ROS,LPO,SOD,MDA,4-HNE,GSH and Fe2+in the myocardial tissues of rats in each group;RT-PCR detected the expression levels of iron-death-related genes,FTH1,SLC7A11,and GPX4 mRNA expression levels in the myocardial tissues of rats.Results Ershen Tang improved collagen fibre proliferation and reduced inflammatory cell infiltration in myocardial tissues;increased the activities of GSH and SOD(P<0.05),decreased the levels of ROS,LPO,MDA,and 4-HNE(P<0.05),and reduced the level of Fe2+(P<0.01);promoted the expression of FTH1,GPX4,and SLC7A11 mRNA(P<0.05).Conclusion Ershen Tang was able to reduce myocardial tissue damage in rats with coronary heart disease,and its mechanism may be related through inhibiting ferroptosis of cardiomyocytes.
基金项目
2022年度吉林省科技厅自然科学基金项目(YDZJ202201ZYTS209)