冠状动脉微栓塞后大鼠心肌组织炎症细胞因子表达和心功能的动态变化及关系

Altered Expression of Myocardial Inflammatory Cytokines and Their Association With Myocardial Function in Coronary Microembolization Rats

目的:探讨大鼠冠状动脉微栓塞(CME)后心肌组织中炎症细胞因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β及IL-10的表达和心功能动态变化及其关系。方法:经左心室心尖部注射42μm的微球,建立大鼠CME模型。将大鼠随机分为CME组和假手术组,以注射生理盐水为假手术组(每组n:50)。按CME后3 h、6 h、12 h、24 h、4周共5个时间点(各时间点n=10)分为不同时间观察。采用逆转录——聚合酶链反应和免疫组织化学方法检测各组大鼠微栓塞后不同时间点心肌组织内TNF-α、IL-1β、IL-10的动态表达规律及其与心功能变化的关系。结果:CME组与假手术组比较,在CME后3 h、6 h、12 h、24 h心肌组织中TNF-α、IL-1β和IL-10信使核糖核酸、蛋白表达均升高,差异均有统计学意义(P均<0.05)。心脏超声显示与假手术组比较,CME组在微栓塞后3 h、6 h、12 h、24 h和4周的左心室射血分数均下降,差异均有统计学意义(P均<0.05)。CME组中3 h、6 h、12 h、24 h TNF-α信使核糖核酸(mRNA)和IL-1βmRNA表达量分别与左心室射血分数呈显著负相关(P均<0.05)。CME组内各时间点微梗死面积和炎症细胞浸润比较差异无统计学意义(P均>0.05)。结论:CME后TNF-α、IL-1β和IL-10在心肌组织中表达均显著增高,并在微栓塞后12 h达到高峰,24 h后明显下降。同时心功能也随着炎症细胞因子的变化而改变,提示CME后心肌组织TNF-α、IL-1β等炎症细胞因子表达的显著增加在心肌损伤中发挥重要作用。

Objective ： To evaluate the changes of myocardial inflammatory cytokines and their association with myocardial dysfunction in rats after coronary microembolization （CME）. Methods： A total of 10 Rats were randomly divided into Coronary microembolization CME） group and Sham group, n = 5 in each group. 42μm micro spheres were injected into rat＇s left ventricle during 10 seconds occlusion of the ascending aorta to make CME model. Expression of myocardial inflammatory eytokines and myocardial function were evaluated at 3 h, 6 h, 12 h,24 h, and 4 weeks time points after CME in each group. Myocardial inflammation was evaluated by accounting the number of infiltrated inflammatory cells in myocardium and by analyzing the myocardial cytokines of tumor necrosis factor-α （TNF-α ） , interleukin-1 β（IL-1β） and anti-inflammatory cytokine interleukin-10 （IL-10）. Myocardial function was detected by echocardiography. Results： The levels of TNF-α ,IL-1β and IL-10 in CME group were markedly increased compared with Sham group at 3 h, 6 h, 12 h and 24 h time points （P 〈 0.05 ）, the peak level appeared at the 12 h time point while markedly decreased at 24 h time point. No differences were found at 4 weeks time point （ P 〉 0. 05 ） between two groups. Echocardiography showed that the left ventricular ejection fraction （LVEF） in CME group was significantly decreased compared with Sham group at each time point. There was an negative correlation between the expression of TNF-α mRNA ,IL-1β mRNA and LVEF at 3 h,6 h, 12 h,24 h time point respectively in CME group. The inflammatory cell infiltration in CME group was markedly increased compared with Sham group （ P 〈 0. 05 ）. Conclusion： TNF-α ,IL-1β and IL-10 in myocardium were significantly increased after CME. Such increase might play an important role in myocardial dysfunction.