Nix在血小板线粒体自噬以及巨核细胞分化中的作用及其分子机理研究

Nix is regarded as a receptor of mitophagy, and mitochondrion can not be eliminated efficiently in mice with Nix deletion during the process of erythrocyte maturation. Our latest results demonstrated that the number of platelets increased and platelet activation was impaired in mice with Nix deletion. We hypothesize that there is dysfunction of platelet mitophagy in mice with Nix deletion, which results in impaired platelet function. Platelet mitophagy was analyzed in mice with Nix deletion to understand roles and mechanisms of Nix-mediated mitophagy in megakaryocyte differentiation, platelet generation, platelet activation and platelet apoptosis under hypoxia or FCCP induction conditions in the present project. Mega01 cell line with Nix knock-down was employed to explore role of Nix in megakaryocyte differentiation and platelet generation. Polymorphism of Nix in platelets of hemorrage and thrombotic patients was detected to analyze correlation between dysfunction of platelet mitophagy and platelet related diseases and the underlying possible mechanisms. The present study will not only provide better basis for studying roles of Nix in megakaryocyte differentiation and platelet mitophagy, but also may provide new theory evidence for the diagnosis of platelet related diseases.

Nix被认为是线粒体自噬（mitophagy）的受体，Nix基因缺失的小鼠表现出红细胞成熟过程中线粒体不能被有效清除。我们最新的研究显示，Nix缺失的小鼠血小板数目增加，血小板活化的功能受损。我们推测Nix缺失的小鼠血小板线粒体自噬异常，并由此导致血小板功能障碍。本研究采用Nix基因敲除的小鼠分析血小板线粒体自噬的机制，了解Nix介导的线粒体自噬在巨核细胞分化，血小板成熟，血小板活化和血小板凋亡中的作用和分子机理。利用基因敲低的Mega01巨核细胞系分析Nix在巨核细胞分化以及血小板成熟中的作用。分析出血和血栓患者血小板Nix基因的多态性，了解线粒体自噬异常与血小板疾病发生的相关性及可能的分子机制。本研究的实施将为Nix在巨核细胞分化以及血小板线粒体自噬的研究提供良好的基础，并有可能为血小板相关疾病的诊断提供新的理论依据。

Nix被认为是线粒体自噬（mitophagy）的受体。Nix缺失的小鼠血小板数目增加，血小板活化的功能受损。我们推测Nix缺失的小鼠血小板线粒体自噬异常，并由此导致血小板功能障碍。本研究采用Nix基因敲除的小鼠分析血小板线粒体自噬的机制，阐明了Nix介导的线粒体自噬在巨核细胞分化，血小板成熟，血小板活化和血小板凋亡中的作用和分子机理。本研究的实施将为Nix在巨核细胞分化以及血小板线粒体自噬的研究提供良好的基础。