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首页> 外文期刊>Expert opinion on therapeutic targets >A specific inhibitor of plasminogen activator inhibitor-1 suppresses rat autoimmune myocarditis.
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A specific inhibitor of plasminogen activator inhibitor-1 suppresses rat autoimmune myocarditis.

机译：纤溶酶原激活物抑制剂1的特异性抑制剂可抑制大鼠自身免疫性心肌炎。

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OBJECTIVE: Myocarditis is a serious disease, however no effective treatment exists. Plasminogen activator inhibitor-1 (PAI-1) is critical in cell recruitment and inflammation. Although inflammation is an essential pathological feature of acute myocarditis, the effects of PAI-1 inhibition on the development of acute myocarditis have not been well studied. METHODS: To clarify the role of PAI-1, we used a rat experimental autoimmune myocarditis (EAM) model. Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. The rats with induced EAM were treated with the PAI-1 inhibitor (IMD-1622) (n = 8) or not treated (n = 6); hearts were harvested on day 21. Echocardiograms, heart weight to body weight ratios (H:B), histological examinations and in vitro studies were performed. RESULTS: Echocardiograms indicated that the PAI-1 inhibitor improved left ventricular fractional shortening (50 +/- 3%) compared with controls (36 +/- 4%, p < 0.05). The inhibitor significantly reduced H:B ratios compared with controls. Pathologically, areas of myocardial cell infiltration and fibrosis in the inhibitor-treated group were significantly smaller than those in the control group. Immunohistochemistry revealed enhanced expression of adhesion molecules and inflammatory factors in non-treated EAM hearts, the inhibitor suppressed this expression. CONCLUSIONS: The PAI-1 inhibitor suppressed EAM development; thus this inhibitor is promising for treating clinical myocarditis.
机译：目的：心肌炎是一种严重的疾病，但是尚无有效的治疗方法。纤溶酶原激活物抑制剂1（PAI-1）在细胞募集和炎症中至关重要。尽管炎症是急性心肌炎的基本病理特征，但对PAI-1抑制作用对急性心肌炎发展的影响尚未得到很好的研究。方法：为了阐明PAI-1的作用，我们使用了大鼠实验性自身免疫性心肌炎（EAM）模型。在第0天用猪心肌肌球蛋白免疫Lewis大鼠以建立EAM。用PAI-1抑制剂（IMD-1622）治疗（n = 8）或未治疗（n = 6）诱导EAM的大鼠;在第21天收集心脏。进行了超声心动图检查，心脏重量与体重之比（H：B），组织学检查和体外研究。结果：超声心动图显示PAI-1抑制剂与对照组（36 +/- 4％，p <0.05）相比，改善了左心室分数缩短（50 +/- 3％）。与对照相比，该抑制剂显着降低了H：B比率。病理上，抑制剂治疗组的心肌细胞浸润和纤维化面积明显小于对照组。免疫组织化学显示在未治疗的EAM心脏中粘附分子和炎性因子的表达增强，该抑制剂抑制了该表达。结论：PAI-1抑制剂抑制了EAM的发展。因此，该抑制剂有望用于治疗临床心肌炎。

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