摘要
目的探讨辣椒素(CAP)对心脏缺血再灌注损伤的保护作用及可能机制。方法 24只SD雄性大鼠随机分为4组(n=6):(1)对照组,(2)缺血再灌注组(IR组),(3)CAP干预缺血再灌注组(CAP+IR组),(4)辣椒素受体拮抗剂辣椒平(CAPZ)预处理后加CAP干预缺血再灌注组(CAPZ+CAP+IR组)。采用大鼠离体心脏Langendorff灌流方法,再灌注30min末以左室发展压(LVDP)和左室舒张末压(LVEDP)评价心脏功能。测定再灌注开始后前5min冠脉流出液中乳酸脱氢酶(LDH)的含量。再灌注120min后取心脏,采用2、3、5-氯化三苯基四氮唑(TTC)染色法评价心肌梗死面积的变化;HE染色观察心肌纤维形态学变化;线粒体氧化应激检测试剂盒检测超氧化物歧化酶(SOD)和丙二醛(MDA)。再灌注10min取心脏组织,Western blot检测细胞色素c和caspase-3蛋白表达。结果与对照组相比,IR组LVEDP升高、LVDP降低(P<0.01),心肌梗死面积增大(P<0.01),心肌纤维排列紊乱,线粒体SOD活性降低、MDA质量摩尔浓度增加(P<0.01),冠脉流出液中LDH含量增多(P<0.01),caspase-3、细胞色素c蛋白的表达量增加(P<0.01);与IR组比较,CAP+IR组LVEDP降低、LVDP部分恢复(P<0.01),心肌梗死面积减小(P<0.01),心肌纤维断裂减少,线粒体SOD活性增加,MDA质量摩尔浓度减少(P<0.01),冠脉流出液中LDH含量减少(P<0.01),caspase-3和细胞色素c蛋白表达量降低(P<0.01);但CAPZ可阻断CAP的上述保护作用。结论 CAP可通过降低线粒体氧化应激减少缺血再灌注引起的细胞坏死和凋亡,改善心脏功能,减轻大鼠离体心脏缺血再灌注损伤。
Objective To investigate the role of capsaicin （CAP） in myocardial ischemia reperfusion injury and its underlying mechanisms. Methods Twenty-four adult male SD rats were randomized into 4 groups, namely the control group, ischemia reperfusion group, ischemia reperfusion with CAP group, and ischemia reperfusion with CAPZ and CAP group. Isolated rat hearts underwent Langendorff perfusion. Left ventricular end-diastolic pressure （LVEDP） andleft ventricular developed pressure （LVDP） was calculated to evaluate myocardial performance at 30 rain of reperfusion. Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium at 120 rain reperfusion. The morphological changes in myocardial fiber was analyzed by HE staining at the end of reperfusion. Lactate dehydrogenase （LDH） content in the coronary flow was determined during the first 5 min reperfusion. The myocardial mitochondria was isolated and extracted for measuring a series of indicators of mitochondrial oxidative stress, including superoxide dismutase （SOD）, methane dicarboxylic aldehyde （MDA） at the end of reperfusion. Western blot was used to determine the expression of caspase-3 and cytochrome c at 10 min reperfusion. Results Compared with the control group, IR group significantly decreased in cardiac function, the level of LVDP and SOD activity and induced an enlarged infarct size （P〈0.01）, accompanied by the disordered arrangement of myocardial ceils, the content of MDA was increased （P〈0.01）, the content of caspase-3 and cytochrome c were also up-regulated （P〈0.01）. 10 mol/L CAP significantly attenuated these effects induced by ischemia reperfusion injury, levels of LVDP and infarct size at the end of reperfusion were significantly improved（P〈0.01）, nevertheless levels of LVEDP and MDA at the end of reperfusion and LDH were down-regulated markedly （P〈0.01）, the content of caspase-3 and cytochrome c were also decreased （P〈0.01）. Conclusion These results demonstrate that CAP can suppresses cell apoptosis and necrosis, and alleviate heart function and cell survival from ischemia reperfusion injury through attenuating mitochondrial oxidative stress.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2017年第5期716-720,共5页
Journal of Sichuan University(Medical Sciences)
基金
陕西省教育厅科研基金(No.15JK1639)
陕西省科技厅科研基金(No.2014JM2-8164)
西安医学院博士科研启动基金项目(No.2015DOC02)资助
关键词
辣椒素
线粒体氧化应激
心脏缺血再灌注损伤
Capsaicin Mitochondria oxidative stress Heart ischemia reperfusion injury
