碳酸酐酶III与重症肌无力发病的相关性及机制的研究

重症肌无力（MG）是一种由抗体介导的、多因素参与的自身免疫性疾病，这可能与乙酰胆碱受体（AChR）抗体和MuSK抗体的产生有关，但还有5－10%的病人病因未明。且目前的抗体机制仍不能解释MG病态的易疲劳等现象。我们前期发现P25蛋白在MG患者骨骼肌中表达降低，并确认P25蛋白是碳酸酐酶III(CAIII)，进一步检测发现CAIII的蛋白和mRNA在MG患者中均有降低，但其与MG发病的相关性及机制尚不清楚。在此基础上，我们拟首先在AChR损伤和MuSK通路损伤的MG细胞模型中观察CAIII的表达变化；然后进一步观察CAIII高表达或功能阻断对AChR数量及聚集功能的影响；最后利用RNA干扰技术抑制在体组织中CAIII或MuSK的表达，探讨CAIII与AChR及MuSK抗体机制间的相互影响。本项目的完成有助于了解CAIII与MG的相关性及作用机制，为MG发病机制的研究提供新的理论依据。

Myasthenia gravis(MG) is an antibodies-mediated, heterogeneous autoimmune disease. Anti-AChR and Anti-MuSK antobodies present in 90%-95% patients. 5-10% patients are still in obscure. And the antibody mechanism still can not explain the fatigue we see in MG patients. Our previous study found that P25 protein is dramaticly reduced in muscles of MG patients. MALDI-TOF suggested P25 is carbonic anhydrase III(CAIII). We subsequently proved that CAIII is reduced in protein and mRNA levels in MG patients, but the mechanism is still unknown. Here we first observe the CA III protein and mRNA levels in AChR and MuSK antibodies treated C2C12 cells. Second, using CAIII over expression or blocked cell models, observe the effect of CAIII over expression and blockage on the AChR quantity and Agrin induced AChR assembly. Finnally using RNA interferrin, observe the AChR and ColQ levels in CAIII silenced models, and the CAIII level in MuSK silenced models in vivo. This study will elucidate the correlation and the possible roles that CAIII plays in the pathogenesis of MG.