乙醛脱氢酶2(ALDH2)是心血管疾病干预的新靶点，目前尚未有针对此靶点的新药上市。牛樟芝(AC)是产于台湾地区的真菌，尚未见AC防治心血管疾病的报道。我们研究发现AC抗脂肪肝的作用依赖于ALDH2基因，通过上调ALDH2酶活性实现，表明AC的作用靶点可能是ALDH2；AC具有抑制野生型小鼠心肌纤维化的作用，伴随心脏ALDH2酶活性上调，4-HNE水平减低，氧化应激抑制，AP-1、TGF-β1和Samd3表达下调，表明AC可能通过上调靶点ALDH2的酶活性促进活性氧清除，抑制线粒体氧化应激对TGF-β1通路的激活而抗心肌纤维化。本课题采用Ang II在野生型和ALDH2敲除小鼠及心脏成纤维细胞上建立心肌纤维化体内和体外模型，研究AC及其单体抗心肌纤维化的作用及机制与ALDH2的关系，阐明AC中单体调控ALDH2酶活性的分子机制。本研究将对发现调控ALDH2靶点的心血管新药具有重要意义。

Aldehyde dehydrogenase 2 (ALDH2) is a new target in intervention for cardiovascular diseases. However, currently there are no new cardiovascular drugs on the market that aim at targeting ALDH2. Antrodia cinnamomea (AC) is a kind of fungus grown in Taiwan, and there are no reported studies about its protective effects on cardiovascular diseases. Preliminary results from our study showed that the inhibitory effects of AC on both alcoholic fatty liver disease and nonalcoholic fatty liver disease were all dependent on the existence of ALDH2 gene, and AC exhibited such effects by upregulating the enzyme activity of ALDH2, indicating that ALDH2 could be the probable therapeutic target of AC. In addition, AC was found having inhibitory effects on myocardial fibrosis in wild type mice, which was accompanied by upregulation of ALDH2 enzyme activity, decrease of 4-hydroxynonenal, suppression of mRNA expression of genes related to oxidative stress, as well as downregulation of mRNA expression of AP-1, TGF-β1 and Samd3. These phenomena suggest that AC probably upregulated the enzyme activity of its potential target, ALDH2, to scavenge reactive oxygen species, therefore inhibited activation of the TGF-β1 pathway induced by mitochondrial oxidative stress, finally led to the prevention of myocardial fibrosis. In this research project, we will use angiotensin II to induce myocardial fibrosis in both wild type and ALDH2 knockout mice, as well as in primary cardiac fibroblasts. The inhibitory effects and related mechanisms of AC and its active compounds on myocardial fibrosis, and the role of ALDH2 therein will be investigated on these in vivo and in vitro myocardial fibrosis models. Moreover, the molecular mechanisms behind the regulation of ALDH2 enzyme activity by the active compounds in AC will be revealed. Our study will be of great significance to the discovery of new cardiovascular drugs that target ALDH2.