腺苷介导大鼠心脏缺血后适应的保护效应

Cardioprotection with ischemic postconditioning mediated by adenosine in rats

目的观察大鼠心肌缺血再灌注时NFκ-B mRNA表达和炎性细胞因子的变化及腺苷后适应对其影响,初步探讨腺苷后适应对缺血再灌注损伤心肌的保护机制。方法健康雄性SD大鼠48只随机分为4组:假手术组、缺血再灌注组、缺血后处理组及腺苷后适应组,每组12只,建立大鼠心肌缺血再灌注模型。光镜下观察心肌组织形态学改变;TTC染色计算各组大鼠心肌梗死面积;RT-PCR检测心肌NF-κB mRNA表达水平,ELISA测定组织中TNF-α及白细胞介素6(IL-6)含量。结果假手术组心肌组织无改变,缺血再灌注组心肌损伤较重,腺苷后适应组及缺血后处理组心肌组织病理学改变明显减轻。与缺血再灌注组比较,腺苷后适应组NF-κB mRNA的表达水平、心肌梗死面积及TNF-α与IL-6的含量明显降低(P<0.01);与缺血后处理组比较,腺苷后适应组NFκ-B mRNA表达及TNF-α、IL-6的分泌均下降(P<0.05)。NFκ-B mRNA的表达与心肌中TNF-α、IL-6浓度呈正相关(P<0.01)。结论腺苷后适应可抑制再灌注后心肌NF-κB的表达活化,从而通过促使炎性细胞因子TNFα-、IL-6分泌减少来减轻缺血再灌注损伤。

Objectives To observe the effects of adenosine postconditioning on the expression of NF-κB mRNA and changes of inflammatory factors in myocardial ischemia-reperfusion（IR） injury,and investigate the protective mechanism of adenosine postconditioning against myocardial ischemia -reperfusion injury. Methods Forty-eight healthy male SD rats were randomly divided into four groups（ n = 12 each） ：sham operation group, IR group,ischemic post-conditioning（IPTC） group and adenosine postconditioning（ADOP） group. The model of myocardial ischemia-reperfusion was established. Light microscope was used to observe tissue changes of myocardium,and infarct size（TTC staining）, NF-κB mRNA（RT-PCR）, TNF-α, IL-6 （ELISA） were measured at the end of ischemia-reperfusion. Results Compared with IR group,myocardial infarct size,expression of NF-κB mRNA and the concentrations of TNF-α and IL-6 in myocardial tissue in ADOP group decreased markedly（ P d0.01）. Moreover, the myocardial pathological damage was also relieved obviously in ADOP and IPTC group, but the difference between ADOP group and IPTC group was not significant （ P 〉 0. 05）, except that the expression of NF-κB mRNA and secretion of TNF-α,IL-6 in ADOP group were a little lower than those in IPTC group（ P 〈0.05）. NF-κB mRNA level in myocardium was correlated positively with the concentrations of TNF-α （r = 0.713, P〈0.01） and IL-6（ r =0. 642, P 〈0. 01）. Conclusion ADOPcaninhibitthesecretionof inflammatory factors induced by activated NF-κB after reperfusion to attenuate myocardial ische- mia-reperfusion injury.