病毒性心肌炎发病率高，慢性迁延导致的扩张型心肌病(DCM)病死率高，治疗棘手。心肌纤维化是其重要病理改变。我们前期发现钙离子依赖性的半胱氨酸蛋白酶(calpain)可诱导病毒性DCM小鼠心肌纤维化，机制不清。NF-ΚB活化与纤维化密切相关，而乙酰化修饰是其活性调节的重要方式。既往报道组蛋白去乙酰基酶(HDAC3)是调控NF-ΚB乙酰化的关键靶点。新近我们发现在病毒性DCM中，Calpain可上调HDAC3表达，并引起NF-ΚB活化。故提出假说：Calpain通过诱导NF-ΚB乙酰化，促进心肌纤维化。为了弄清其机制，本项目拟进一步在细胞、过表达calpain内源性抑制蛋白小鼠模型上研究CVB3感染后calpain不同亚型活性变化对心肌纤维化的作用，明确calpain特异性亚型对NF-ΚB乙酰化调控的分子机制，有望揭示calpain促进心肌纤维化的新机制，为临床DCM诊治靶标的探寻提供新思路。

One of the malignant outcomes of viral myocarditis is its progression into dilated cardiomyopathy (DCM). The prognosis of DCM are poor; however, the treatment of DCM is still lack of specific measures. And myocardial fibrosis is the important pathological changes in DCM. Our previous study has shown that calcium dependent cysteine protease (calpain) induce myocardial fibrosis in the mice with CVB3-induced DCM; however, the detailed mechanism is not clear. Nuclear factor-ΚB (NF-ΚB) is closely related to fibrosis, and acetylation is reported to play an important role on the regulation of NF-ΚB activity. Several investigations have shown that histone deacetylase 3 (HDAC3) is a key to regulate the acetylation of NF-ΚB. Recently, we have found that calpain can increase HDAC3 expression and activate NF-ΚB in the murine model of CVB3-induced DCM. Therefore, we propose the hypothesis that calpain contributed to myocardial fibrosis through increasing acetylation of NF-kB. To explore the potential mechanisms, we will furtherly study the effects of subtypes of calpain on myocardial fibrosis after CVB3 infection in vivo and in vitro, and the mechanisms on calpain-regulated the acetylation of NF-ΚB. The study is expected to reveal the new mechanisms on calpain-induced myocardial fibrosis in DCM and provide the novel ideas for the treatment of DCM.