七氟醚后处理调节HIF-1α/BNIP3通路减轻小鼠心肌缺血/再灌注损伤的机制  

Mechanism of sevoflurane postconditioning in modulating hypoxia inducible factor-1α/B cell lymphoma 2/adenovirus E1B protein-interacting protein 3 pathway to alleviate myocardial ischemia-reperfusion injury in mice

作　　者：凌征海 梁栋 杨雪 任炳楠 于文彬 王江[1] 吴建江[1] Ling Zhenghai;Liang Dong;Yang Xue;Ren Bingnan;Yu Wenbin;Wang Jiang;Wu Jianjiang(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,乌鲁木齐830054

出　　处：《国际麻醉学与复苏杂志》2023年第12期1244-1251,共8页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金(81760044)。

摘　　要：目的探究七氟醚后处理(sevoflurane postconditioning,SpostC)是否通过调控缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)/B细胞淋巴瘤2/腺病毒E1B相互作用蛋白3(B cell lymphoma 2/adenovirus E1B protein-interacting protein 3,BNIP3)通路,进而减轻小鼠心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MIRI)的分子机制。方法将40只小鼠按随机数字表法分为4组(每组10只):假手术组(Sham组)、心肌缺血再灌注组(I/R组)、七氟醚后处理+I/R组(SpostC组)和七氟醚后处理+HIF-1α抑制剂(2ME2)+I/R组(SpostC+2ME2组)。Sham组只穿线不结扎冠状动脉左前降支(left anterior descending coronary artery,LAD)。I/R组结扎LAD 30 min,再灌注120 min。SpostC组和SpostC+2ME2组在复灌即刻吸入1 MAC七氟醚15 min,然后再灌105 min。SpostC+2ME2组在LAD结扎前腹腔注射2ME2,剂量为15 mg/kg。采用心脏超声检测心脏功能,记录舒张期左心室前壁厚度(left ventricular end-diastolic anterior wall thickness,LVAWd)、收缩期左心室前壁厚度(left ventricular end-systolic anterior wall thickness,LVAWs)、射血分数(ejection fraction,EF)、左心室缩短分数(fractional shortening,FS)、舒张期左心室后壁厚度(left ventricular end-diastolic posterior wall thickness,LVPWd)、收缩期左心室后壁厚度(left ventricular end-systolic posterior wall thickness,LVPWs)、舒张期左心室内径(left ventricular internal dimension at end-diastolic,LVIDd)和收缩期左心室内径(left ventricular internal dimension at end-systolic,LVIDs);H-E染色观察心肌组织结构;TTC+伊文蓝染色法测定心肌梗死面积;ELISA法检测血清肌型肌酸激酶(creatine kinase M-type,CKM)、肌钙蛋白T型2(troponin T-type 2,TNNT2)、肌酸激酶同工酶(creatine kinase-MB,CK-MB)和乳酸脱氢酶(lactate dehydrogenase,LDH)的表达水平;透射电镜观察线粒体超微结构改变情况;Western blot法检测心肌组织中HIF-1α、BNIP3、微管相关蛋白轻链3-Ⅱ(microtubule-associatedObjective To investigate whether sevoflurane postconditioning(SpostC)alleviates myocardial ischemia/reperfusion(I/R)injury in mice by regulating the hypoxia inducible factor-1α(HIF-1α)/B cell lymphoma 2/adenovirus E1B interacting protein 3(BNIP3)pathway,in order to relieve myocardial ischemia reperfusion injury(MIRI)in mice.Methods According to random number table method,40 mice were divided into four groups(n=10):a Sham group,a myocardial ischemia reperfusion(I/R)group,a sevoflurane postconditioning+I/R group(SpostC)group,a sevoflurane postconditioning group+HIF-1αblocker(2ME2)+I/R(SpostC+2ME2)group.Sham group was only threaded without ligation of the left anterior descending coronary artery(LAD).LAD was ligated for 30 min and reperfused for 120 min in I/R group.In SpostC group and SpostC+2ME2 group,1 MAC sevoflurane was inhaled for 15 min immediately after reperfusion,and then reperfused for 105 min.In SpostC+2ME2 group,2ME2 was injected intraperitoneally at a dose of 15 mg/kg before LAD ligation.Cardiac ultrasound was utilized to evaluate cardiac function,including left ventricular end-diastolic anterior wall thickness(LVAWd),left ventricular end-systolic anterior wall thickness(LVAWs),ejection fraction(EF),fractional shortening(FS),left ventricular end-diastolic posterior wall thickness(LVPWd),left ventricular end-systolic posterior wall thickness(LVPWs),left ventricular internal dimension at end-diastolic(LVIDd),and left ventricular internal dimension at end-systolic(LVIDs).The structure of myocardial tissue was observed by H-E staining.The myocardial infarction size was measured by TTC+Evans Blue double staining.The levels of serum lactate dehydrogenase(LDH),creatine kinase M-type(CKM),creatine kinase isoenzyme(CK-MB),and troponin T-type 2(TNNT2)were detected by enzyme-linked immunosorbent assay(ELISA).The changes of mitochondrial ultrastructure were observed by transmission electron microscopy.The levels of HIF-1α,BNIP3,microtubule-associated protein light chain 3Ⅱ(LC3-Ⅱ),autophagy-related protein(

关 键 词：七氟醚 后处理 缺氧诱导因子-1Α 心肌再灌注损伤 

分 类 号：R965[医药卫生—药理学]