青年和老年小鼠脑缺血再灌注心肺损伤的机制  

Mechanism of heart and lung injury induced by cerebral ischemia/reperfusion in both young and old mice

作　　者：吕燕妮[1] 付龙生 钱贻崧[2] 江明金[1] 何礼标[1] 欧阳爱军[1] 郑宇[1] 

机构地区：[1]南昌大学第一附属医院药学部,江西南昌330006 [2]南昌大学转化医学研究院心血管疾病研究中心,江西南昌330001

出　　处：《细胞与分子免疫学杂志》2017年第6期800-806,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：江西省卫生计生委科技计划项目(20175081)

摘　　要：目的研究小鼠脑缺血再灌注心肺组织损伤情况及机制。方法按5~6月龄和20~21月龄,将C57BL/6J小鼠分为青年和老年组。实验组设立假手术组,模型组为缺血1 h再灌注1、12、24、48 h组。取各灌注时间点的小鼠心肺组织,HE和TUNEL染色观察形态学改变,化学比色法检测心脏Na^+-K^+-ATP酶、Ca^(2+)-ATP酶变化,称重法计算肺指数,Western blot法分别检测心肺组织中核因子κBp65(NF-κBp65)、磷酸化NF-κBp65(p-NF-κBp65)、核因子κB抑制蛋白α(IκBα)、磷酸化IκBα(p-IκBα)水平,ELISA检测白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平,比色法测定一氧化氮(NO)水平。结果青年和老年小鼠分别在再灌注24 h和再灌注1 h发生肺部炎症反应,而分别于再灌注24 h和再灌注12 h可见心脏出血,肺对再灌注刺激的反应比心脏组织更早。同时在对Na^+-K^+-ATP酶、Ca^(2+)-ATP酶、肺指数、NF-κB信号通路与炎症因子的测定发现,这些指标在青年和老年小鼠组上的变化与其病理组织变化时程一致。结论老年小鼠脑缺血再灌注后会引起心肺组织的损伤,能量代谢和炎症级联反应为其损伤的主要机制。Objective To study the mechanism of heart and lung injury after cerebral ischemia/reperfusion in mice. Methods C57BL/6J mice were divided into young and old groups according to their ages, the former being 5 -6 months old and the latter being 20 - 21 months old. Each group was divided into five subgroups subjected to sham operation, middle cerebral artery occlusion for 1-hour ischemia followed by 1-,12-, 24-, 48-hour reperfusion. At different reperfusion time, HE and TUNEL staining were used to observe the morphological changes of heart and lung tissues; meanwhile, chemical colorimetry was performed to determine the changes of cardiac Na ^＋ -K^ ＋ -ATPase and Ca^2＋ -ATPase; the lung indexes were evaluated ; the levels of nuclear factor （NF） -KBp65, p-NF-KBp65, IKBα, p-IKBα were detected by Western blotting; the levels of interleukin 16 （IL-1β）, tumor necrosis factor α （TNF-α） were determined by ELISA; and the release of NO was examined by colorimetry. Results We observed inflammatory responses in the lung tissues of young and old mice at 24-hour reperfusion and 1-hour reperfusion, respectively, and hemorrhage in the heart tissues of young and old mice at 24-hour reperfusion and 12-hour reperfusion, respectively. Lung tissues showed earlier response to the stimulation of cerebral ischemia/ reperfusion than heart tissues did. Meanwhile, the results of Na ^＋ -K ^＋ -ATPase, Ca^2 ＋ -ATPase, lung index, NF-KB signaling pathway and inflammatory cytokines in young and old mice were consistent with histological changes of heart and lung tissues. Conclusion Cerebral ischemia/reperfusion can cause heart and lung tissue injury in the old mice, and energy metabolism and inflammation cascade are the main mechanisms of the injury.

关 键 词：脑卒中后并发症 大脑中动脉栓塞模型 心肺损伤 老年小鼠 炎症级联反应 

分 类 号：R541.5[医药卫生—心血管疾病] R743.33[医药卫生—内科学]