针灸临床杂志2025，Vol.41Issue(4)：80-87,8.DOI:10.19917/j.cnki.1005-0779.025076
基于SLC7A11/GPX4通路探讨电针预处理对心肌缺血再灌注损伤大鼠心肌细胞铁死亡的影响
Effect of EA Pretreatment on Ferroptosis of Myocardial Cells in Rats with MIRI Based on SLC7A11/GPX4 Pathway
摘要
Abstract
Objective:To observe the effect of electro-acupuncture(EA)pretreatment on ferroptosis of myocardial cells in rats with myocardial ischemia-reperfusion injury(MIRI)and to explore its possible mechanism.Methods:A total of45 SD rats were randomly divided into the Sham operation(Sham)group,the model(MIRI)group and the model plus EA pretreatment group(MIRI+EA),with 15 rats in each group.After 1 week of adaptive feeding,bilateral Neiguan(PC6),Zusanli(ST36)and Guanyuan(RN4)were subjected to EA intervention for 20 min in the MIRI+EA group,once a day for 7 consecutive days,and the rats in the other groups were bound for 20 min without other intervention,once a day for 7 consecutive days.MIRI rat model was established in all rats on the 8th day.In the Sham group,sutures passed below the anterior descending branch of the left coronary artery without ligation.After modeling,the myocardial infarction size was detected by TTC staining,the pathological changes of cardiomyocytes were observed by HE staining,the mitochondrial ultrastructure changes were observed by transmission electron microscopy,and the levels of ferrous(Fe2+),reduced glutathione(GSH)and oxidized glutathione disulfide(GSSG)were detected by kits.Flow cytometry was used to detect ROS level in ischemic myocardium.Western blot assay was used to detect the expressions of 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),transferrin receptor 1(TFR1),ferritin heavy chain 1(FTH1)and long chain fatty acyl CoA synthetase 4(ACSL4).Immunohistochemical staining(IHC)was used to detect the protein expressions of SLC7A11 and GPX4 in ischemic myocardial tissues.Results:The results of HE staining and transmission electron microscopy showed that myocardial fiber breakage,cell swelling,mitochondrial ridge breakage and mitochondrial membrane breakage in the MIRI group,and the pathological changes in the MIRI+EA group were significantly reduced.Compared with those in the Sham group,the myocardial infarction area was significantly increased(P＜0.01),the levels of ROS and Fe2+were significantly increased(P＜0.01),the level of GSH/GSSG was significantly decreased(P＜0.01),the protein expressions of TFR1 and ACSL4 were significantly up-regulated(P＜0.01),the protein expressions of FTH1,SLC7A11 and GPX4 were significantly down-regulated(P＜0.01),and the positive protein expressions of SLC7A11 and GPX4 in myocardial cytoplasm were significantly decreased in the MIRI group(P＜0.01).Compared with those in the MIRI group,the myocardial infarction area was significantly decreased(P＜0.01),the levels of ROS and Fe2+were decreased(P＜0.01,P＜0.05),the level of GSH/GSSG was significantly increased(P＜0.01),the protein expressions of TFR1 and ACSL4 were down-regulated(P＜0.01,P＜0.05),the protein expressions of FTH1,SLC7A11 and GPX4 were significantly up-regulated(P＜0.01),and the positive protein expressions of SLC7A11 and GPX4 in myocardial cytoplasm were increased in the MIRI+EA group(P＜0.01,P＜0.05).Conclusion:EA pretreatment may alleviate the ferroptosis of cardiomyocytes induced by free iron accumulation,ROS accumulation and lipid peroxidation by up-regulating SLC7A11/GPX4,thereby improving MIRI.关键词
心肌缺血再灌注损伤/电针预处理/铁死亡/SLC7A11/GPX4Key words
MIRI/EA pretreatment/Ferroptosis/SLC7A11/GPX4分类
医药卫生引用本文复制引用
张艳琳,吴松,路珍,韦禹岐,郭倩茹..基于SLC7A11/GPX4通路探讨电针预处理对心肌缺血再灌注损伤大鼠心肌细胞铁死亡的影响[J].针灸临床杂志,2025,41(4):80-87,8.基金项目
国家中医药管理局青年岐黄学者培养项目,编号:国中医药人教函[2022]256号 （）
全国名老中医药专家传承工作室建设项目,编号:国中医药人教函[2022]75号. （）
