CAJ | 학술논문

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.
목적 게시휴대중조인백세포개소-10적2형선상관병독(AAV2-rhIL-10)전염대서심기후고표체적rhIL-10시부능개선심기경사후좌심실중구화공능.방법 웅성성년SD대서수궤분위대조조(n=6)、급성심기경사+AAV2-rhIL-10주사조(MI/AAV2-IL-10조,n=16)화급성심기경사+AAV2주사조(MI/AAV2조,n=16).비교각조재초성심동도、혈류동역학、효원용적분수(CVF)、Ⅰ、Ⅲ형효원용적분수등방면적차별.결과 AMI후4주,MI/AAV2-IL-10조대서심장공능교MI/AAV2조명현개선.MI/AAV2-IL-10조교MI/AAV2조경사원격구CVF、Ⅰ형효원용적분수화Ⅰ/Ⅲ형효원적비례명현하강(P<0.01).MI/AAV2-IL-10조적Ⅰ형효원mRNA표체화MMP-2mRNA표체명현하강,분별위P<0.05화P<0.01.결론 전염AAV2-rhIL-10인기적rhIL-10표체증가가이감소심기경사후심기조직효원침적,최종개선좌심실공능.
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-rhIL-10) and AAV2 were injected around the ischemic zone. Echocardiography parameters, hemodynamic parameters, left ventricular mass index (LVMI) , collagen volume fraction (CVF) , perivascu-lar 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 echocardiography 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-rhIL-10 transfection of rats' myocardium promotes LV remodeling and cardiac function after acute myocardial infarction. The promotion was partially achieved by inhibition myocardium collagen deposition.