Growing evidences have revealed that a histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA) has anti-fibrotic effect in different diseases. In this study, we first evaluated whether SAHA could suppress cardiac fibrosis. Mice with MI-induced cardiac fibrosis were treated with SAHA by intraperitoneal injection and their cardiac function was improved after SAHA treatment. Results of western blotting and qRT-PCR in heart tissues suggested that TGFβ1/P38 pathway was activated in MI mice, and this effect was reversed by SAHA. Cell proliferation assay suggested that SAHA could suppress TGF-β1-induced cardiac fibroblasts proliferation. Furthermore, results of western blotting and qRT-PCR in cardiac fibroblasts depicted that SAHA may exert its anti-fibrotic effect through inhibiting TGF-β1-induced P38 phosphorylation by promoting DUSP4 expression. Our findings may substantiate SAHA as a promising treatment for MI-induced cardiac fibrosis.

越来越多的证据表明，组蛋白去乙酰化酶抑制剂 (HDACi)、辛二酰苯胺异羟肟酸 (SAHA) 在不同疾病中具有抗纤维化作用。在这项研究中，我们首先评估了 SAHA 是否可以抑制心脏纤维化。用SAHA腹腔注射治疗MI诱导的心脏纤维化小鼠，SAHA治疗后心脏功能得到改善。心脏组织中的蛋白质印迹和 qRT-PCR 结果表明，在 MI 小鼠中，TGFβ1/P38 通路被激活，而这种作用被 SAHA 逆转。细胞增殖试验表明SAHA可以抑制TGF-β1诱导的心脏成纤维细胞增殖。此外，心脏成纤维细胞中的蛋白质印迹和qRT-PCR结果表明SAHA可能通过促进DUSP4表达抑制TGF-β1诱导的P38磷酸化来发挥其抗纤维化作用。我们的研究结果可能证实 SAHA 作为 MI 诱导的心脏纤维化的有希望的治疗方法。