【摘要】 目的:探讨心肌梗死后不同阶段非梗死区心肌胶原的变化及其发生机制。方法:雌性Wistar大鼠,通过结扎左冠状动脉前降支制备心肌梗死模型。分为心肌梗死组(最终存活32只)和假手术组(最终存活47只),于术后24h、1周、2周及4周随机从两组中各取10~12只大鼠,分别行病理组织学、心肌胶原容积密度分数(CVF)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)、血管紧张素Ⅱ(AngⅡ)和醛固酮(ALd)水平的分析,以及Ⅰ型胶原(col-1)及Ⅲ型胶原(col-3)的信使核糖核酸(mRNA)检测。结果:大鼠梗死范围为24%~33%。心肌组织Messon染色显示,假手术组间质只可见散在亮绿色胶原;术后24h~1周,心肌梗死组间质亮绿色胶原与假手术组基本相似;术后2~4周最明显。肿瘤坏死因子-α的表达在梗死后1~4周显著增强。心肌血管紧张素Ⅱ水平术后1~4周,心肌梗死组均高于假手术组,有显著性差异(P<0.05~0.001)。心肌醛固酮含量术后2~4周,心肌梗死组也明显于高假手术组,有显著性差异(P<0.05~0.001)。Ⅰ型胶原mRNA水平术后2~4周心肌梗死组明显高于假手术组;Ⅲ型胶原mRNA水平术后1~4周心肌梗死组明显高于假手术组(P均<0.05)。基质金属蛋白酶-9表达无变化。结论:①大鼠心肌梗死2周后非梗死区出现明显间质纤维化。②非梗死区间质纤维化可能与局部肾素血管紧张素醛固酮系统激活后增加血管紧张素Ⅱ水平及肿瘤坏死因子-α上调有关。③大鼠心肌梗死后4周内非梗死区基质金属蛋白酶-9表达无明显变化。更多还原

【Abstract】 Objective:To investigate the changes of interstitial collagen in non-infarct zone(NIZ)and elucidate the mechanisms of the changes in an infarcted rat model.Methods:The rats undergoing sham operation or left coronary artery ligation were killed 24 hours,1,2 and 4 weeks after operation.Infarct size,interstitial collagen volume fraction(CVF),Tumor necrosis factor α(TNF-α),Matrix metalloproteinase(MMP)-9,AngⅡ and Aldosterone(ALD)were measured.Expression of genes encoding collagen type 1 and collagen type 3 were measured by reverse transcriptase-polymerase chain reaction(RT-PCR)methods.Results:The myocardial infarction(MI)group exhibited increased non-infarct zone in CVF from 2 to 4 weeks(P< 0.05-0.01).The levels of TNF-α and AngⅡwere increased from 1 to 4 weeks(P<0.05-0.001).The level of ALD were increaed from 2 to 4 weeks(P<0.05-0.001).The gene expression of collagen type 1 was more obvious from 2 to 4 weeks(P<0.05).The gene expression of collagen type 3 was more obvious from 1 to 4 weeks(P<0.05-0.01).The change of MMP-9 was not obvious(P>0.05).Conclusion:There was interstitial fibrosis in non-infarct zone at 14 days after MI in rats,which might be associated with augmentation of Ang Ⅱ due to the activation of RAAS and the upregulation of TNF-α.The MMP-9 in non-infarct zone had no changes within the 4 weeks.更多还原