天香丹减轻心肌缺血损伤的作用机制研究  

Study on the mechanism of action of tianxiangdan in reducing myocardial ischemic injury

作　　者：岳远佳 姜林 吉钊 王慧敏 杜古加·嘎尔玛 荣幸 Yue Yuanjia;Jiang Lin;Ji Zhao;Wang Huimin;Dugujia Gaerma;Rong Xing(Fourth College of Clinical Medicine,Xinjiang Medical University,Urumqi 830000,China;不详)

机构地区：[1]新疆医科大学第四临床医学院,乌鲁木齐830000 [2]省部共建中亚高发病成因与防治国家重点实验室,乌鲁木齐830000 [3]新疆中药炮制研究重点实验室,乌鲁木齐830000

出　　处：《中国循证心血管医学杂志》2024年第1期35-38,共4页Chinese Journal of Evidence-Based Cardiovascular Medicine

基　　金：国家自然科学基金(81960699);省部共建中亚高发病成因与防治国家重点实验室开放课题资助项目(SKL-HIDCA-2020-8)。

摘　　要：目的研究天香丹胶囊激活雌激素受体α(ERα)抑制铁死亡减轻心肌缺血损伤的机制。方法将70只SD雌性大鼠(210±40)g随机分组,建立去势模型,灌胃60 d,可逆性结扎冠状动脉(冠脉)左前降支30 min,进行心功能数据实时监测;检测血清中雌激素和cTnI含量;检测心肌组织中丙二醛(MDA)、氧化型谷胱甘肽(GSH-PX)、超氧化物歧化酶(SOD)、Fe2+含量;苏木精-伊红(HE)染色观察心肌组织形态;Western blot检测心肌中的蛋白ERα、长链脂酰CoA合成酶4(ACSL4)、谷胱甘肽过氧化物酶4(GPX4)、铁蛋白重链1(FTH1)。结果去势后,各组比空白组雌激素水平显著降低;在给药60 d后,给药组比模型组雌激素水平升高,而肌钙蛋白(cTnI)含量降低;给药组比模型组Fe2+、MDA含量降低,GSH-PX、SOD含量增加;HE染色显示给药组对心脏表现出不同程度的保护作用;Western blot结果显示给药组比模型组中ERα、GPX4、FTH1的蛋白表达增强,而ACSL4蛋白的表达显著减小,差异有统计学意义(P<0.05)。结论通过上述试验推测天香丹胶囊激活ERα,升高GPX4、FTH1表达,降低ACSL4表达,降低氧化应激水平,抑制铁死亡,从而减轻心肌缺血损伤。Objective To study the mechanism of Tianxiang Dan Capsule alleviating myocardial ischemia(MI)through activating estrogen receptorα(ERα)for inhibiting ferroptosis.Methods SD female rats[n=70,weighted(210±40)g]were randomly divided into groups,and emasculated model was established and gavaged with medicinal for 60 d.The left anterior descending branch(LAD)of coronary artery was reversibly ligated for 30 min,and data of heart function was given real-time monitoring.The levels of serum estrogen,cardiac troponin I 2+(cTnI),malondialdehyde(MDA),glutathione peroxidease(GSH-PX),superoxide dismutase(SOD)and Fe were detected.The myocardial tissue morphology was observed after HE stain.The levels of myocardial Erα,ACSL4,GPX4 and FTH1 were detected by using Western blotting assay.Results After emasculated,estrogen level decreased significantly in different groups compared with blank group.After medicated for 60 d,estrogen level 2+increased and cTnI level decreased in all medicated groups compared with model group.The levels of Fe and MDA decreased,and GSH-PX and SOD increased in all medicated groups compare with model group.The results of HE stain observation showed that heart was protected in varying degrees in all medicated groups.The results of Western blotting assay showed that the protein expression of ERα,GPX4 and FTH1 increased and ACSL4 protein expression decreased in all medicated groups compared with model group(P<0.05).Conclusion Based on the above experiments,it is speculated that Tianxiang Dan Capsule can alleviate myocardial ischemia injury through activating Erα,elevating expressions of GPX4 and FTH1,reducing ACSL4 expression,cutting down oxidative stress and inhibiting ferroptosis.

关 键 词：天香丹 雌激素受体Α 铁死亡 心肌缺血 

分 类 号：R542.2[医药卫生—心血管疾病]