氯沙坦干预病毒性心肌炎恢复期、慢性期心脏胶原表达及心功能的实验研究

目的观察病毒性心肌炎恢复期、慢性期心脏间质胶原表达及其对心功能的影响，并初步探讨药物干预的效果，为临床干预心肌纤维化提供实验依据。方法建立恢复期、慢性期病毒性心肌炎小鼠模型，通过阻抗微分法观察心排血量，Ｈ．Ｅ染色及苦味酸天狼猩红胶原特异染色偏振光显像进行心脏间质胶原的组织化学观察，ＲＴＰＣＲ观察心脏Ｉ型胶原ｍＲＮＡ表达的变化，并与氯沙坦（ｌｏｓａｒｔａｎ）干预后比较。结果病毒性心肌炎恢复期心脏胶原增生，心排血量降低，氯沙坦干预后胶原表达无论从蛋白水平还是从ｍＲＮＡ水平均明显降低，但心排血量未见明显改善；病毒性心肌炎慢性期心脏胶原大量增生，心排血量降低，氯沙坦干预后胶原表达无论从蛋白水平还是从ｍＲＮＡ水平均明显降低，心排血量改善，与正常对照组比较差异无显著性。结论病毒性心肌炎恢复期可能存在修复性纤维化和反应性纤维化两种胶原增生状态，二者对心功能的影响不同，这可能是氯沙坦消除增生的胶原后心脏功能不见明显改善的原因。病毒性心肌炎慢性期胶原蛋白增生为单纯性反应性纤维化，使心排血量下降，氯沙坦部分阻逆反应性增生胶原，可提高心排血量，改善心脏功能。

Expression of myocardial collagen and cardiac function in recovery and chronic stage of viral myocarditis: Losartan intervention study

Objective To investigate the remodeling of myocardial interstitial collagen in mice with viral myocarditis (VMC) at revovery and chronic stage and its effects of cardiac function, preliminarily probe the feasibility of drug intervention, offer the experimental evidence for clinic to intervene the fibrosis of heart interstitium.Methods The mice model with VMC was established. CO was measured by impedance differential plethysmography, myocardial interstitial collagen was observed by staining with H.E. and Sirius Red in a supersaturated picric acid solution viewed by polarization microscopy. The changes of mRNA expression of collagen type I were analyzed by RT PCR. The results were compared with those after intervention with Losartan.Results Myocardial collagen proliferated significantly and CO decreaed in two stages of VMC, and the expression of collagen mRNA and protein decreased remarkably after intervention with Losartan. In chronic stage, CO was improved after intervention with Losartan and there was no significant difference compared with normal control, but after intervention in recovery stage, CO was no significant difference compared with VMC that without intervening markably, CO improved. Conclusion At recovery stage, there could be two kinds of fibrosis course: reparative fibrosis and reactive fibrosis, the effect of these two courses may offset each other, this may be the reason why no influnence of cardiac index was observed. At chronic stage, collagen increased widely which is the result of reactive fibrosis, the proliferous collagen impaired greatly the cardiac function. Intervening by Losartan could improve cardiac function through suppressing reactive fibrosis during chronic phase of viral myocarditis.