Resistin基于PI3k-Akt和MAPK通路参与重症肌无力CD4+辅助性T细胞亚群失衡的研究

CD4+辅助性T细胞-细胞因子网络失衡在重症肌无力（MG）致病中起重要的作用，而PI3k-Akt和MAPK通路是细胞因子诱导其失衡的重要信号通路。Resistin作为前炎症因子，可启动多个炎症信号通路，诱导大量的细胞因子表达，进而通过相互间的协同作用引起CD4+辅助性T细胞亚群失衡，促进炎症的发展。我们前期已发表的研究发现，乙酰胆碱受体抗体阳性的全身型MG患者Resistin水平明显升高，且Resistin与疾病严重程度呈正相关，免疫治疗后水平显著下降，提示Resitin可能参与了MG的致病过程。此外，细胞水平的预实验发现Resistin可诱导Th1/Th2亚群比例升高。本课题拟在前期基础上，以MG病人及实验性自身免疫性重症肌无力小鼠为媒介，进一步阐明Resistin基于PI3k-Akt和MAPK通路参与MG CD4+辅助T细胞亚群失衡，并探索以Resistin为靶点的分子治疗。

An imbalance in the CD4+ helper T cell-cytokine network, principally induced by two pathways, the PI3k-Akt and MAPK pathways, plays a key role in the pathogenesis of myasthenia gravis (MG). Increased levels of resistin, a proinflammatory cytokine, can induce secretion of various cytokines via different inflammatory signaling pathways such as NF-κB, PI3K, and MAPK pathways. Potential interactions among cytokines underlying the imbalance of CD4+ helper T cell have been identified; however, the role of resistin in MG has not been reported. Previously, we demonstrated that levels of resistin were significantly elevated in patients with acetylcholine receptor antibody-positive MG (AChR-MG). We also observed correlations between serum resistin and MG-ADL scores in patients with AChR-generalized MG; and the resistin levels declined after immunosuppressive therapy. In addition, our preliminary studies showed that resistin can induce an increase in the Th1/Th2 subsets. In the present study, we will investigate the role and molecular mechanisms of resistin with respect to the PI3k-Akt and MAPK pathways in patients with MG and in experimental autoimmune myasthenia gravis (EAMG) mouse model, and investigate whether resistin may be a potential target for MG treatment.