我们发现SIRT1激活在心血管保护中发挥重要作用，还证实SIRT1介导姜黄素抗心脏缺血再灌注损伤，激活SIRT1可抑制多种因素诱导的心肌肥厚。CTRP3是脂肪细胞因子CTRP超家族成员，可调控细胞内一系列分子，进而减轻心梗后的心肌重构，而这些分子跟SIRT1联系密切，提示CTRP3与SIRT1通路间可能有交互关系。近期我们发现：①大鼠心肌肥厚后CTRP3表达下调；②CTRP3敲除可以加重压力负荷下大鼠的心肌肥厚，且伴随SIRT1表达下调；③姜黄素发挥抗心肌肥厚作用伴随CTRP3表达上调。以上证据强烈提示：CTRP3可能是逆转心肌肥厚的重要分子，可以通过调控SIRT1通路发挥抗心肌肥厚作用。本项目将从在体（敲除和转基因大鼠）、细胞与分子水平研究证实CTRP3-SIRT1信号通路在逆转心肌肥厚中的作用，为寻找全新的抗心肌肥厚靶点和开发以姜黄素为基础的心肌保护药物奠定理论基础。

Previously, we have confirmed silent information regulator 1 (SIRT1) is an important cardioprotective molecule, and that activation of SIRT1 by curcumin can attenuate myocardial ischemia reperfusion injury (IRI). Studies have found that activation of SIRT1 can inhibits the progression of cardiac hypertrophy induced by angiotensin II and phenylephrine, etc. C1q/tumor necrosis factor-related protein-3 (CTRP3), a member of the CTRP superfamily, is a novel identified adipokine which exerts multiple cardioprotective roles. Importantly, Activation of CTRP3 can alleviate the myocardial remodeling of rat after acute myocardial infarction, which may be related to the regulation of a number of intracellular molecules (e.g. AMPK, Akt, PKA, eNOS, BAD, etc). In addition, those intracellular molecules regulated by CTRP3 have multiple interactions with SIRT1 signaling, suggesting CTRP3 may interact with SIRT1 signaling pathway. Interestingly, our preliminary experiments documented that CTRP3 knockout rat shows down-regulation of SIRT1 and aggravating myocardial hypertrophy under excessive pressure load, but curcumin could alleviate its progression through up-regulating CTRP3. These evidences strongly suggest that CTRP3 may be the key molecular in reversing the progression of myocardial hypertrophy through regulating SIRT1 signaling pathway. In this study, CTRP3 knockout and/or transgenic rat and cell line will be used to investigate the role of CTRP3-SIRT1 pathway in inhibiting myocardial hypertrophy, and to further explore the interaction or up-downstream relationships between CTRP3 and SIRT1 signalings. In the meantime, we will focus on the CTRP3-SIRT1 signaling in alleviating myocardial hypertrophy performed by curcumin. Above all, this study will provide new anti-hypertrophic target and theoretical basis for curcumin to inhibit myocardial hypertrophy.