白细胞介素-10抑制大鼠急性心肌梗死后左心室心肌胶原沉积

IL-10 inhibits myocardium collagen deposition after acute myocardial infarction in rats

目的揭示携带重组人白细胞介素-10的2型腺相关病毒(AAV2-rhIL-10)转染大鼠心肌后高表达的rhIL-10是否能改善心肌梗死后左心室重构和功能。方法雄性成年SD大鼠随机分为对照组(n=6)、急性心肌梗死+AAV2-rhIL-10注射组(MI/AAV2-IL-10组,n=16)和急性心肌梗死+AAV2注射组(MI/AAV2组,n=16)。比较各组在超声心动图、血流动力学、胶原容积分数(CVF)、Ⅰ、Ⅲ型胶原容积分数等方面的差别。结果AMI后4周,MI/AAV2-IL-10组大鼠心脏功能较MI/AAV2组明显改善。MI/AAV2-IL-10组较MI/AAV2组梗死远隔区CVF、Ⅰ型胶原容积分数和Ⅰ/Ⅲ型胶原的比例明显下降(P<0.01)。MI/AAV2-IL-10组的Ⅰ型胶原mRNA表达和MMP-2mRNA表达明显下降,分别为P<0.05和P<0.01。结论转染AAV2-rhIL-10引起的rhIL-10表达增加可以减少心肌梗死后心肌组织胶原沉积,最终改善左心室功能。

Objective To test the hypothesis that IL-10 may promoting left ventricular remodeling and cardiac function by modulating extracellular matrix after acute myocardial infarction. Methods Male adult rats were randomly divided into three groups ： control group （ n = 6 ）, MI/AAV2 group （ n = 16 ） and MI/AAV2-IL-10 group （ n = 16）. Establishing animal modol of experimental myocardial infarction and recombinant adeno-associated virus type 2 （AAV）/IL-10 （AAV2-rhlL-10） and AAV2 were injected around the ischemic zone. Echocardiography parameters, hemodynamic parameters, left ventricular mass index （LVMI）, collagen volume fraction （CVF） , perivascular circumferential area （PVCA） , collagen type Ⅰ ＆Ⅲ volume fraction and mRNA levels of collagen type Ⅰ ＆Ⅲ, matrix metalloproteinases-2 （MMP-2） and tissue inhibitor of metalloproteinase-1 （ TIMP-1 ） were compared among the three groups. Results Improved cardiac function was observed in MI/AAV2-IL-10 group shown by echocardio- graphy and hemodynamic examination. Four weeks after myocardial infarction, thickness of different parts of LV was not different in MI/AAV2-IL-10 group and MI/AAV2 group. Nevertheless CVF, PVCA and collagen type I volume fraction was significantly descending in remote zone of MI/AAV2-IL-10 group compared with that of MI/ AAV2 group. The mRNA expression of collagen type I and MMP-2 was lower in MI/AAV2-IL-10 group than that in MI/AAV2 group. Conclusion Recombinant IL-10 expression mediated by AAV2-rhlL-10 transfection of rats＇ myo- cardium promotes LV remodeling and cardiac function after acute myocardial infarction. The promotion was partially achieved by inhibition myocardium collagen deposition.