脂联素在自身免疫性心肌炎中的抗炎效应及相关机制研究

项目名称： 脂联素在自身免疫性心肌炎中的抗炎效应及相关机制研究

项目编号： No.81460067

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 韦传东

作者单位： 右江民族医学院

项目金额： 47万元

中文摘要： 自身免疫性心肌炎是造成扩张型心肌病、心力衰竭等重症心脏病的主要原因，严重危害人类健康，目前仍无特效治疗手段。研究表明，Thl7细胞介导炎症细胞浸润及炎症因子分泌表达是造成心脏损伤的主要病因，血液中脂联素(APN)水平与炎症性疾病呈明显负相关。APN是一种具有广泛抗炎、抗心肌损伤效应的蛋白质激素，课题组在前期研究发现球状APN（gAPN）不仅可通过激活PI3K/Akt信号、抑制ERK1/2信号活性来抵抗棕榈酸诱导H9c2细胞的凋亡；而且能抵抗TNF-α诱导H9c2细胞的凋亡。因此，本课题拟在前期研究的基础上，进一步探索gAPN抵抗TNF-α诱导H9c2细胞凋亡的作用机制；并通过建立自身免疫性心肌炎大鼠模型，探讨外源性gAPN如何通过调节Th17细胞分化来减少自身免疫性心肌炎对心脏的损伤；期望能为APN作为心肌炎性心肌病预防和治疗的新靶点提供理论依据。

中文关键词： 脂联素；心肌炎；H9c2；细胞；JAKs/STATs；细胞凋亡

英文摘要： Autoimmune Myocarditis is a serious hazard of common diseases to human health. It is a major cause of dilated cardiomyopthy, heart failure, and other severe heart disease. Currently, there is still no specific treatment for Autoimmune Myocarditis. Studies have shown that Thl7 cell-mediated infiltration of inflammatory cell and secretion of inflammatory cytokine is a major cause of heart damage in Autoimmune Myocarditis, and the level of serum adiponectin was significantly negatively correlated in inflammatory diseases. APN is a hormone of protein, and have a broad anti-inflammatory, anti-myocardial damage effects. Applicants found that global APN (gAPN) not only can resist apoptosis of H9c2 cells induced by palmitate via activation of PI3K/Akt signaling, and inhibiting ERK1/2 signaling activity, but also can resist apoptosis of H9c2 cells induced by TNF-α. The topic intends to further explore the special mechanism involved in gAPN H9c2 resist apoptosis of H9c2 cells induced by TNF-α, and then to study that the gAPN how to regulate Th17 cells differentiation to reduce the damage of heart in the rat model of autoimmune myocarditis, which would provide a theoretical basis for APN as a new target for prevention and treatment in Inflammatory cardiomyopathy.

英文关键词： Adiponectin;myocarditis;H9c2 cell;JAKs/STATs;Apoptosis