甘草苷抑制急性心肌梗死大鼠心肌细胞铁死亡的作用研究  

Effect of liquiritin on inhibiting ferroptosis of myocardial cells of rats with acute myocardial infarction

作　　者：周佳[1] 陈远园[1] 朱瑶蕾 王国栋 ZHOU Jia;CHEN Yuanyuan;ZHU Yaolei;WANG Guodong(Department of Geriatrics,Hangzhou Hospital of Traditional Chinese Medicine affiliated to Zhejiang Chinese Medical University,Hangzhou 310007,China)

机构地区：[1]浙江中医药大学附属杭州市中医院老年病科,310007

出　　处：《浙江医学》2024年第18期1910-1917,共8页Zhejiang Medical Journal

基　　金：浙江省医药卫生科技计划项目(2023KY199)。

摘　　要：目的探讨甘草苷对急性心肌梗死(AMI)大鼠心肌细胞铁死亡的作用及调控机制。方法动物体内实验:将大鼠按照随机数字表法分为假手术组(0.9%氯化钠溶液)、AMI模型组(建模后0.9%氯化钠溶液灌胃)、低剂量组(建模后40 mg/kg甘草苷灌胃)和高剂量组(建模后80 mg/kg甘草苷灌胃)后,3组大鼠均在左心耳下端距离冠状动脉左前降支2 mm处进行结扎,构建AMI大鼠模型。观察并比较4组大鼠给药7 d后心肌缺血面积、组织病理学改变、心肌损伤标志物[血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)]水平、铁死亡标志物[活性氧(ROS)、谷胱甘肽(GSH)、Fe^(2+)、丙二醛(MDA)]水平及沉默调节蛋白3(SIRT3)、谷胱甘肽过氧化物酶4(GPX4)、溶质载体家族7成员11(SLC7A11)表达水平。体外细胞实验:将培养的H9c2细胞分别设空白组、模型组、低剂量组(40μmol/L甘草苷)、高剂量组(80μmol/L甘草苷)、高剂量+Erastin组(80μmol/L甘草苷+5μmol/L Erastin)、高剂量+si-NC组(80μmol/L甘草苷+0.8μg si-NC)和高剂量+si-SIRT3组(80μmol/L甘草苷+0.8μg si-SIRT3)予相应药物预处理;除空白组外,其余5组均进行低氧处理(1%O_(2)、5%CO_(2)、94%N2)建立缺氧细胞模型。观察并比较6组细胞活性、细胞凋亡率、铁死亡标志物及SIRT3、GPX4、SLC7A11蛋白表达水平。结果动物体内实验结果显示,与AMI模型组比较,低剂量组和高剂量组心肌组织损伤减轻且梗死面积较小,低剂量组和高剂量组CK、CK-MB、cTnI、MDA、ROS和Fe^(2+)水平均下降,GSH、SIRT3、GPX4和SLC7A11表达水平均升高(均P<0.05)。体外细胞实验结果显示,与模型组比较,低剂量组和高剂量组细胞活性、GSH、SIRT3、GPX4和SLC7A11表达水平均升高(均P<0.05),细胞凋亡率、MDA、ROS和Fe^(2+)水平均降低(均P<0.05)。与高剂量组比较,高剂量+Erastin组和高剂量+si-SIRT3组细胞活性、GSH、SIRT3、GPX4和SLC7A11表达水平均降低(均P<Objective To investigate the effect of liquiritin on ferroptosis of myocardial cells of rats with acute myocardial infarction(AMI)and its corresponding regulatory mechanism.Methods In vivo animal experiment:the rats were divided into sham operation group(0.9%sodium chloride solution),AMI model group(intragastric administration of 0.9%sodium chloride solution after modeling),low-dose liquiritin group(40 mg/kg liquiritin by gavage after modeling)and high-dose liquiritin group(80 mg/kg liquiritin by gavage after modeling)according to the random number table method,with 6 rats in each group.Except for the sham operation group,the other three groups were ligated at the position of 2 mm from the lower end of the left atrial appendage to the left anterior descending branch of the coronary artery in order to construct the AMI rat models.The changes of myocardial ischemia area,histopathological changes,myocardial injury biomarker levels[serum creatine kinase(CK),creatine kinase isoenzyme(CK-MB),and cardiac troponin I(cTnI)],ferroptosis biomarkers levels[reactive oxygen species(ROS),glutathione(GSH),Fe^(2+),and malondialdehyde(MDA)],and the expression levels of silent information regulator 3(SIRT3),glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)proteins were detected and compared among the four groups after 7 days of administration.In vitro cell experiment:the cultured H9c2 cells were divided into blank group,model group,low-dose liquiritin group(40μmol/L liquiritin),high-dose liquiritin group(80μmol/L liquiritin),high-dose liquiritin+Erastin group(80μmol/L liquiritin+5μmol/L Erastin),high-dose liquiritin+si-NC group(80μmol/L liquiritin+0.8μg si-NC),and high-dose liquiritin+si-SIRT3 group(80μmol/L liquiritin+0.8μg si-SIRT3).Except for the blank group without any treatment,the other five groups were treated with hypoxia(1%O_(2),5%CO_(2),and 94%N2)to establish the anoxic cell models.The cell viability,apoptosis rate,the levels of ferroptosis biomarkers of ROS,GSH,Fe^(2+),and MDA,and the e

关 键 词：甘草苷 沉默调节蛋白3 急性心肌梗死 铁死亡 

分 类 号：R285.5[医药卫生—中药学]