鸢尾素上调Akt/Nrf2抑制铁死亡减轻阿霉素诱导的心肌损伤  

Irisin Upregulates Akt/Nrf2 to Inhibit Ferroptosis Alleviating Doxorubicin-induced Myocardial Injury

作　　者：阿依提拉·外力 张子龙[2] 施安哲 郭睿青[1] 玛依拉·吾麦尔 Ayitila·Waili;ZHANG Zilong;SHI Anzhe(Department of Electrocardiographic Function,First People′s Hospital of Kashgar Region,Xinjiang Uygur Autonomous Region,Xinjiang 844000,China;不详)

机构地区：[1]新疆维吾尔自治区喀什地区第一人民医院心电功能科,844000 [2]新疆维吾尔自治区人民医院心内科,乌鲁木齐830001

出　　处：《医学研究杂志》2024年第9期74-79,共6页Journal of Medical Research

基　　金：新疆维吾尔自治区自然科学基金资助项目(2023D01C181)。

摘　　要：目的探讨鸢尾素对阿霉素(doxorubicin,DOX)诱导的心脏损伤的作用及其机制。方法选取C57BL/6J雄性小鼠30只,将其随机分为空白组、DOX组和鸢尾素治疗组,每组各10只。每5天腹腔注射1次DOX(5mg/kg),总计20mg/kg诱导心肌损伤;空白组给予等比例0.9%氯化钠溶液;鸢尾素治疗组提前1周每天腹腔注射鸢尾素[1mg/(kg·d)],之后DOX处理的同时注射鸢尾素(1mg/kg)。实验过程中记录小鼠生存率,存活的小鼠在第21天检测心功能,计算心脏重量与胫骨长度比值。酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血浆肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)、乳酸脱氢酶(lactate dehydrogenase,LDH)和肌钙蛋白(cardiac troponin,cTnT)水平;苏木精-伊红(hematoxylin-eosin,HE)染色观察心肌结构;Masson染色观察心肌纤维化;试剂盒检测心肌丙二醛(malondialdehyde,MDA)、还原型谷胱甘肽(reduced glutathione,GSH)/氧化型谷胱甘肽(oxidized glutathione,GSSG)含量及超氧化物歧化酶(superoxide dismutase,SOD)活性;实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)检测心脏炎性细胞因子白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达;Western blot法检测蛋白激酶B(Akt)及其磷酸化水平、核转录相关因子2(nuclear transcription-related factor 2,Nrf2)、谷胱甘肽氧化酶4(glutathione oxidase 4,GPx4)及酰基辅酶A合成酶长链家族成员4(acyl-CoA synthetase long chain family member 4,ACSL4)水平。结果DOX组小鼠生存率降低,左心室射血分数和短轴缩短率明显低于空白组,左心室舒张末期容积增大,心脏重量与胫骨长度比值下降,血浆CK-MB、LDH和cTnT上升,并伴组织水肿、炎性浸润及纤维增生。同时,DOX组心脏MDA和GSSG含量高于空白组,GSH水平和SOD活性则低于空白组,伴随高水平炎症和氧化应激。鸢�Objective To investigate the role of irisin on doxorubicin(DOX)-induced cardiac injury and its mechanism.Methods Thirty male C57BL/6J mice were selected and randomly divided into blank group,DOX group and irisin treatment group,with 10mice in each group.Myocardial injury was induced by intraperitoneal injection of DOX(5mg/kg)every five days,with a total of 20mg/kg;the blank group was given an equal proportion of normal saline;the irisin treatment group was injected intraperitoneally with irisin[1mg/(kg·d)]every day for one week in advance,and irisin(1mg/kg)was injected at the same time as the DOX treatment.The survival rate was recorded during the experiment,and the surviving mice were tested for cardiac function on the twenty-first day,and the ratio of heart weight to tibia length was calculated.Enzyme-linked immunosorbent assay(ELISA)was used to detect the plasma creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),and cardiac troponin(cTnT)levels;hematoxylin-eosin(HE)staining was used to observe the myocardial structure;Masson staining was used to observe the myocardial fibrosis;and kit was used to detect myocardial malondialdehyde(MDA),reduced glutathione/oxidized glutathione(GSH/GSSG)levels and superoxide dismutase(SOD)activity;real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect cardiac inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)expression;Western blot was used to detect protein kinase B(Akt)and its phosphorylation(p-Akt)level,nuclear transcription-related factor 2(Nrf2)and glutathione oxidase 4(GPx4)and acyl-CoA synthetase long chain family member 4(ACSL4)levels.Results The survival rate of DOX group was decreased,left ventricular ejection fraction and short-axis shortening rate were significantly lower than those in the blank group,left ventricular end-diastolic volume was increased,the ratio of heart weight to tibia length was decreased,and the plasma CK-MB,LDH,and cTnT were increased,accompanied by tissu

关 键 词：鸢尾素 阿霉素 心肌损伤 铁死亡 

分 类 号：R541[医药卫生—心血管疾病]