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

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。

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

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(10～20 μg/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 myocardium.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.Conclusion 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.