CTRP3介导LAMP1-JIP2-JNK信号通路保护心肌缺血/再灌注损伤

MI/RI是心肌缺血后心肌损伤加重的重要原因。脂肪因子CTRP3是新发现的保护MI/RI的重要分子，其在肝癌细胞系的受体是溶酶体相关膜蛋白1。迄今CTRP3心肌受体及其下游分子仍知之甚少。我们的预实验结果提示：溶酶体相关膜蛋白1和JNK在CTRP3保护MI/RI起重要作用。为此，我们提出假说：CTRP3通过受体溶酶体相关膜蛋白1、JNK相互作用蛋白2及JNK保护MI/RI。为了验证这一假说，我们通过小鼠心肌细胞、大鼠心肌细胞缺氧/复氧和小鼠MI/RI模型，采用LRC-TriCEPS技术，Western blot、腺病毒载体转染、RNA干扰等手段，从分子、细胞、组织以及动物整体水平等多方面探讨CTRP3在MI/RI的重要作用，明确CTRP3通过减轻氧化/硝化应激保护MI/RI的调控机制。本研究将从CTRP3这个新视点为揭示MI/RI的保护机制奠定基础，为冠心病及其并发症的防治提供新的思路。

MI/RI is important reason in aggravating damage after myocardial ischemia. CTRP3 played a major role in the protecting of MI/RI. Lysosomal-associated membrane protein 1( LAMP1) is receptors which mediate the hepatic actions of CTRP3. Our previous studies showed LAMP1 and Jun N-terminal kinase(JNK) played a important role in protecting of MI/RI. Thus, we speculate that CTRP3 may decrease MI/RI through LAMP1-JNK Interacting Protein 2(JIP2)-JNK signal pathway.We planed to construct anoxia/reoxygenation injury mice myocardial cell model and MI/RI model in mice and use LRC-TriCEPS / Western blot/adenovirus vector transfection/ RNA interfering technology to reveal the role of CTRP3 in MI/RI and elucidate the regulatory mechanism of CTRP3 in decreasing the oxidation/nitrification stress.Therefore, the present study may reveal mechanism of protecting of MI/RI and provide a new idea to prevention and cure CHD from a new perspective of CTRP3.