白细胞介素10在心肌缺血再灌注损伤中对细胞凋亡的作用及机制研究  

The effect of IL-10 on cardiomyocyte apoptosis during myocardial ischemia-reperfusion injury and its mechanism

作　　者：褚松筠[1] 丁文惠[1] 胡春阳[1] 蔡大勇[2] 马铁民[2] 唐朝枢[2] 

机构地区：[1]北京大学第一医院心内科,北京100034 [2]北京大学医学部生理系,北京100083

出　　处：《中华老年心脑血管病杂志》2006年第6期404-407,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：首都医学发展科研基金(2002-2003)

摘　　要：目的探讨心肌缺血再灌注(IR)时应用白细胞介素10(IL-10)是否可减少细胞凋亡及其可能的信号途径。方法SD大鼠40只,分为4组,每组10只。IR组结扎左前降支(LAD)1 h,再灌注2 h造成模型。IL-10干预10μg/kg和20μg/kg 2组在再灌注前15 min静脉给予IL-10。假手术组在LAD下穿线但不结扎。测定梗死面积、血流动力学参数,TUNEL计数凋亡细胞数,Western blot测定caspase-3以及蛋白激酶B(Akt),p38丝裂原激活的蛋白激酶(p38MAPK)磷酸化表达。结果与假手术组比较,IR组显示明确的心肌缺血和梗死区域,且细胞凋亡明显。IL-10干预组减少梗死面积,改善心功能,心肌细胞凋亡减少,caspase-3的激活降低。同时IL-10干预磷酸化Akt表达上调,而磷酸化p38MAPK表达下调。结论IL-10可减少IR导致的心肌细胞凋亡,保护心功能;IL-10干预的保护作用可能影响了caspase-3的激活,通过激活Akt,抑制p38MAPK途径而实现。Objective To investigate whether IL-10 treatment could reduce myocyte apoptosis during myocardial ischemia reperfusion （IR） .Method Forty adult SD rats were assigned randomly to 3 groups. In IR group, the rats were subjected to ligation of LAD for 1 h and subsequent reperfusion for 2 h. In IL-10 intervention group, IL-10 （ 10 - 20μ/kg） was given intravenously at 15 min before reperfusion. In sham operation group, a suture was placed under LAD without ligation. The infarction area was measured and cardiac function was evaluated with hemodynamic monitoring. Apoptosis was estimated by TUNEL staining. Expression of caspase-3, p38 mitogen-activated protein kinase（MAPK） and protein kinase（Akt） was determined by Western blot. Results IR group presented apparent infarction and apoptosis in myocardimn. IL-10 treatment reduced the infarction area and improved the cardiac function as compared with IR group. The results of TUNEL staining indicated that apoptotic myocytes decreased in IL-10 intervention group as compared with IR group. Consistent with these, expression of cleaved caspase-3 decreased in IL-10 group. Also, the expression of phospho-Akt was upregulated while the expression of phospho-p38MAPK was downregulated in IL-10 group. Condusion IL-10 treatment could decrease the infarction area and improve the cardiac function at least partly through decreasing the apoptotic myocytes during myocardial ischemia-reperfusion. The protective effect of IL-10 may be associated with its regulation of Akt and p38MAPK signaling pathways.

关 键 词：心肌缺血 白细胞介素10 再灌注损伤 细胞凋亡 干预 

分 类 号：R541.4[医药卫生—心血管疾病]