尼可地尔后处理对心肌缺血-再灌注损伤大鼠心肌的保护作用  

Protective effect of nicorandil postconditioning on myocardium of rats with myocardial ischemia-reperfusion injury

作　　者：李悦玮[1] 张文琪[2] 孙景辉[1] 张科强[3] 

机构地区：[1]吉林大学第一医院儿内五科,吉林长春130021 [2]吉林大学中日联谊医院心内科,吉林长春130033 [3]吉林大学第二医院医务部,吉林长春130041

出　　处：《吉林大学学报（医学版）》2012年第6期1160-1163,I0014,共5页Journal of Jilin University：Medicine Edition

基　　金：吉林省卫生厅科研基金资助课题(2009z004)

摘　　要：目的:观察尼可地尔后处理对心肌缺血-再灌注损伤(MIRI)大鼠心肌的保护作用,并探讨其作用机制。方法:26只SD大鼠随机分为对照组(8只)、盐酸异丙肾上腺素(ISO)组(8只)和尼可地尔后处理组(10只)。对照组大鼠腹腔注射等量生理盐水,ISO组大鼠腹腔注射ISO 5mg·kg-1,每隔24h重复注射1次,连续注射3d;尼可地尔后处理组于注射ISO 1h后尾静脉注射尼可地尔(1mg·kg-1),每日1次,连续3d。于第3次注射ISO后24h断尾取血后处死,检测各组大鼠血清中乳酸脱氢酶(LDH)、磷酸激酸(CK)活性;常规HE染色观察各组大鼠心肌组织形态学表现;免疫组织化学染色法检测Caspase-3蛋白的表达;TUNEL法检测各组大鼠心肌细胞凋亡情况。结果:尼可地尔后处理组与对照组比较血清LDH和CK活性差异无统计学意义(P>0.05),但2组均低于ISO组(P<0.05)。HE染色,ISO组大鼠局部心肌组织变性坏死,伴有炎细胞浸润;尼可地尔后处理组大鼠坏死心肌细胞明显减少,炎症反应轻微;对照组大鼠心肌无异常表现。免疫组织化学染色,ISO组大鼠大量心肌细胞胞浆表达Caspase-3,对照组和尼可地尔后处理组大鼠Caspase-3无表达。尼可地尔后处理组细胞凋亡指数(AI)较ISO组明显降低(P<0.01)。结论:尼可地尔可减轻大鼠MIRI,其作用机制可能与抑制Caspase-3激活、减少细胞凋亡有关。Objective To explore the protective effect of nicorandil postconditioning on myocardium of rats with myocardial ischemia-reperfusion injury（MIRI） in rats and to discuss its mechanism.Methods 26 SD rats were divided into control group（n=8）,isoproterenol（ISO） group（n=8） and nicorandil postconditioning group（n=10）.The rats in ISO group were injected intraperitoneally with isoproterenol（5 mg·kg-1）at an interval of 24 h for 3 d;the rats in control group only received an injection of same amount of saline;the rats in nicorandil postconditioning group were injected intravenously with nicorandil（1 mg·kg-1） 1 h after ISO injection once a day,lasting for 3 d.The rats were killed 24 h after the third injection of ISO.The activities of serum creatine kinase（CK） and lactate dehydrogenase（LDH） of rats in various groups were detected;the histopathological changes of myocardium of rats in various groups were observed by routine HE staining;the expressions of Caspase-3 protein were determined by immunohistochemistry;the apoptosis of cardiocytes of rats in various groups was analyzed by TUNEL staining.Results There were no significant differences in the activites of serum CK and LDH between nicorandil postconditioning group and control group（P0.05）,but the activities of CK and LDH in control and nicorandil postconditioning groups were lower than those in ISO group（P0.05）.The HE staining results showed local degeneration,necrosis and inflammation in ISO group,but slightly necrosis and inflammation in nicorandil postconditioning group and no pathological changes in control group.Immunohistochemistry staining showed that Caspase-3 was positive in cardiocyte plasma in ISO group;however,there were no Caspase-3 expression in control and nicorandil postconditioning groups.The apoptosis index（AI） in nicorandil postconditioning group was significantly decreased compared with ISO group（P0.01）.Conclusion Nicorandil can attenuate MIRI of rats,and its mechanism may be related to inhibiting

关 键 词：心肌缺血-再灌注损伤 尼可地尔 缺血后处理 药物后处理 细胞凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]