间歇性缺氧预适应通过提高细胞膜修复能力减轻心肌缺血/再灌注损伤

刘彦琪; 李林霞; 白云刚; 焦博; 马进; 余志斌; 王云英

doi:10.12125/j.chj.202203001

间歇性缺氧预适应通过提高细胞膜修复能力减轻心肌缺血/再灌注损伤

Intermittent hypoxic adaptation attenuates myocardial ischemia/reperfusion injury by improving ability of plasma membrane repair

摘要

摘要:
目的探究间歇性低氧预适应(intermittent hypoxia adaptation，IHA)能否通过增强细胞膜修复能力，从而减轻心肌缺血/再灌注(ischemia/reperfusion，I/R)损伤。
方法利用小动物低压舱模拟高空缺氧环境建立低氧预适应模型，将雄性Sprague-Dawley 大鼠随机分为4组，分别为：假手术(Sham)组、假手术+预适应(Sham+IHA)组、缺血/再灌注手术(I/R)组和缺血/再灌注手术+预适应(I/R+IHA)组。预适应7 d后Sham组仅进行开胸手术，冠状动脉左前降支(left anterior descending artery, LAD)挂线不结扎，I/R组结扎LAD 30 min后再灌注12 h。造模成功后对各组大鼠行超声心动图检查，评估心脏结构与功能，以酶联免疫吸附(enzyme linked immunosorbent assay, ELISA)法检测血清乳酸脱氢酶同工酶-1(lactate dehydrogenase isoenzyme-1, LDH-1)、肌酸激酶同工酶-MB(creatine kinase isoenzyme-MB, CK-MB)水平，处死大鼠后苏木素-伊红(hematoxylin-eosin staining, HE)染色观察心肌组织病理变化，免疫荧光法检测心肌组织内MG-53荧光强度，Western blot测定心肌组织MG-53、dysferlin、caveolin-3表达水平。
结果与I/R组相比，I/R+IHA组心肌组织损伤较轻，超声心动图检测各项收缩功能指标均明显升高(P<0.01)，提示IHA处理能明显改善心脏收缩功能。与I/R组相比，I/R+IHA组大鼠心肌MG-53荧光强度明显增加(P<0.05)，dysfelin、MG-53、caveolin-3蛋白表达含量均显著升高(P<0.05)。
结论 IHA处理产生的作用包括降低血清LDH浓度、改善心肌病理学改变、提高心脏收缩功能减轻大鼠心肌I/R损伤，其机制可能与提高细胞膜修复能力有关。

Abstract:
AIM To investigate whether intermittent hypoxic adaptation (IHA) can attenuate myocardial ischemia/reperfusion (I/R) injury by improving the ability of plasma membrane repair.
METHODS Small animal hypobaric chamber was used to simulate different barometric heights. Male Sprague Dawley rats were randomly divided into four groups: Sham, Sham+IHA, I/R, I/R+IHA. After 7 days of IHA, different treatments were used in each group. In I/R group, LAD was ligated for 30 minutes and then reperfusion for 12 hours. The myocardial ischemia/reperfusion injury was assessed with HE staining, echocardiography. The fluorescence intensity of mg-53 in myocardial tissue was detected by immunofluorescence assay. The levels of serum lactate dehydrogenase isoenzyme-1 (LDH-1) and creatine kinase isoenzyme-MB (CK-MB) were detected by enzyme-linked immunosorbent assay (ELISA). The expression of dysferlin, caveolin-3 and MG-53 proteinwere detected by Western Blot.
RESULTS There was no significant difference in all indexes between Sham and Sham+IHA. Compared with those in I/R group, the myocardial injury in I/R+IHA group was lighter, and the systolic function were significantly increased (P<0.01). Compared with those in IR group, the fluorescence intensity of MG-53 in I/R+IHA group was significantly increased (P<0.05), and the expression levels of dysfelin, MG-53 and caveolin-3 protein were significantly increased (P<0.05).
CONCLUSION IHA treatment can reduce myocardial I/R injury by improving the ability of plasma membrane repair in adult SD rats.

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