摘要
目的探讨一氧化碳释放分子-2（CORM-2）对大鼠复苏后心功能不全可能的保护机制。方法建立致颤法建立大鼠心肺复苏模型，健康雄性SD大鼠随机（随机数字法）分为模型（Control）组、CORM-2组、无活性CORM-2（iCORM-2）组和假手术（Sham）组，复苏成功后分别静脉注射等体积（1mL）0．2％DMSO溶液、50μmol／kgCORM-2、50μmol／kgiCORM-2及0．2％DMSO溶液。复苏后12h心脏彩超测量射血分数（EF）和心肌功能指数（MPI）评估心功能，Clark氧电极测定心肌线粒体呼吸，Western blot检测心肌胞浆及线粒体蛋白细胞色素c（cytc）及caspase-3表达。组间比较采用方差分析。结果与Control组比较，复苏后12hCORM-2组EF增高，MPI降低，线粒体Ⅲ态呼吸速率、呼吸控制率（RCR）增高，胞质caspase．3及胞质／线粒体cytc比例降低（P〈0．05）。iCORM-2组上述指标与Control组比较，组间差异无统计学意义（P〉0．05）。结论CORM-2可能通过释放CO，抑制心肌线粒体途径细胞凋亡改善线粒体呼吸功能及复苏后心功能不全。
Objective To investigate the protective role of carbon monoxide releasing molecule-2 （CORM-2） in post-resuscitation myocardial dysfunction （PRMD） in rat models of cardiopulmonary resuscitation （CPR）. Methods Cardiopulmonary resuscitation model was established after cardiac arrest induced by ventricular fibrillation. Male healthy Sprague-Dawley （SD） rats were randomly （random number） divided into 4 groups according to random number table： control group, CORM-2 group, inactive CORM-2 （iCORM-2） group and Sham group, in which the equal volume （1 mL） of 0.2% DMSO, 50 μmol/kg CORM-2, 50 μmol/kg iCORM-2 and 0. 2% DMSO were respectively administered into the rats of these groups after resuscitation. The ejection fraction （EF） of left ventricle and myocardial performance index （MPI） were measured to detect the myocardial function by echocardiography at 12 hours after resuscitation. Mitochondrial respiration was assessed with Clark oxygen electrode at the same time. Western blot was used to determine the ratio of mitochondrial cytochrome c （ cyt c） to cytoplasmic cyt c as well as caspase-3 level. Multiple comparisons were made by analysis of variance. Results Compared with the control group, higher EF and MPI, higher state Ⅲ respiration rate and respiratory control rate （RCR） of mitochondria, and decreased ratio of mitochondrial cytc/cytoplasmic cyt c and lower caspase-3 level were observed in the CORM-2 group （P 〈 0. 05 ）. However, there were no significant differences in above biomarkers found between iCORM-2 group and control group （ P 〉 0. 05 ）. Conclusions The CO released from CORM-2 might improve mitochondrial respiration and PRMD by inhibition of myocardial apoptosis via a mitochondrial pathway.
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2016年第12期1278-1283,共6页
Chinese Journal of Emergency Medicine
基金
福建省自然科学基金面上资助项目（2014J01283）
关键词
心肺复苏
心功能不全
一氧化碳释放分子-2
线粒体呼吸
细胞凋亡
Cardiopulmonary resuscitation
Myocardial dysfunction
Carbon monoxide releasing molecular-2
Mitochondrial respiration
Apoptosis
