上调缺氧诱导因子对老龄小鼠心肌缺血再灌注损伤保护作用的实验研究  

Protective mechanism of upregulating HIF on myocardial ischemia-reperfusion injury in elderly mice

作　　者：邹田田[1] 李艾芳 杨欢[1] 胡云 戴晓雯[1] 古丽尼格尔·艾尔肯 陈春玲[1] ZOU Tiantian;LI Aifang;YANG Huan;HU Yun;DAI Xiaowen;GULINIGEER Aierken;CHEN Chunling(Department of Anesthesiology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,新疆乌鲁木齐830054

出　　处：《陕西医学杂志》2024年第4期439-443,474,共6页Shaanxi Medical Journal

基　　金：新疆维吾尔自治区自然科学基金资助项目(2022D01C228)。

摘　　要：目的:分析上调缺氧诱导因子(HIF)对老龄大鼠心肌缺血再灌注(I/R)损伤的保护机制。方法:选择40只SPF级健康老年雄性C57小鼠为研究对象,适应性饲养1周后将其随机分为A、B、C、D四组,每组各10只。A组不做任何处理,B、C、D组均构建小鼠心肌I/R损伤模型,C组于缺血前2 h腹腔注射100 mg/kg HIF-1α激活剂[二甲基乙二酰基甘氨酸(DMOG)],D组于缺血前2 h腹腔注射15 mg/kg HIF-1α抑制剂[2-甲氧基雌二醇(2-ME2)]。比较四组小鼠给药前、给药1、2 h的心率、心肌收缩张力、左室内压最大上升/下降速率、心肌梗死面积情况,以免疫荧光技术、Western blot检测心肌细胞HIF-1α及α-微管蛋白表达。结果:给药后1、2 h,B组、C组和D组小鼠的心率、心肌收缩张力、左室内压最大上升/下降速率较给药前均降低,且D组低于B组、C组,B组低于C组,差异有统计学意义(均P<0.05)。给药后2 h,B组、D组小鼠心肌梗死面积的危险区/左心室、梗死区/左心室、梗死区/危险区水平均低于C组,且D组低于B组(均P<0.05);B组、C组、D组小鼠的HIF-1α蛋白表达水平均高于A组,且D组低于B组、C组,B组低于C组;C组小鼠的α-微管蛋白表达水平高于A组、B组、D组(均P<0.05),但A组、B组、D组小鼠的α-微管蛋白表达水平比较差异无统计学意义(均P>0.05)。结论:上调HIF可改善心肌I/R损伤小鼠的心脏功能,减少心肌梗死面积,改善HIF-1α及α-微管蛋白表达。Objective:To analyze the protective mechanism of upregulating hypoxia-inducible factor(HIF)on myocardial ischemia-reperfusion injury in aged rats.Methods:Forty SPF grade healthy elderly male C57 mice were selected as the research subjects.After one week of adaptive feeding,the experiment was conducted.Forty mice were randomly divided into four groups,with 10 mice in each group.Among them,Group A did not do any treatment,group B,C,and D all constructed the model of myocardial ischemia-reperfusion injury in mice.In group C,100 mg/kg dimethylglyoxyglycine(DMOG,HIF-1α activator)was intraperitoneally injected at 2 hours before ischemia,and in group D,15 mg/kg 2-methoxyestradiol(2-ME2,HIF-1α inhibitor)was intraperitoneally injected at 2 hours before ischemia.The heart rate,myocardial contractile tension,maximum rate of rise/fall of left ventricle and myocardial infarction area of four groups of mice were compared before administration,1hour after administration and 2 hours after administration.The myocardial HIF-1α and α-microtubulin protein expression was detected by immunofluorescence and Western blot.Results:At 1 and 2 hours after administration,the heart rate,myocardial contraction tension and the maximum rise/fall rate of left ventricular pressure in the group B,C and D were lower than those before administration,and those in the group D were lower than those in the group B and C,and those in the group B were lower than those in the group C(all P<0.05).At 2 hours after administration,the ratio of risk zone in left ventricle,infarct zone in left ventricle,and infarct zone to risk zone in group B and group D were lower than those in group C,and those in group D were lower than those in group B(all P<0.05).The expression level of HIF-1α protein in group B,C and D was higher than that in group A,and that in group D was lower than that in group B and C,and that in group B was lower than that in group C(all P<0.05).The expression level ofα-tubulin in group C was higher than that in group A,B and D(all P<0.05),but

关 键 词：心肌缺血 再灌注损伤 缺氧诱导因子 Α-微管蛋白 老龄小鼠 

分 类 号：R-332[医药卫生]