Vimentin构象改变与自噬的相互调控在Cadmium致血睾屏障破坏作用中的机制研究

课题组前期研究发现镉(Cadmium, Cd)染毒所致的血睾屏障（blood-testis barrier, BTB）破坏中支持细胞波形蛋白（Vimentin, Vim）的表达显著减少，且与自噬活性增高相关。然而，在Cd染毒环境下Vim与自噬相互作用的调控机制尚不明确。自噬通过去除衰老细胞器及吞噬并降解结构异常的蛋白质维持内环境的稳态。我们推测：Cd可能与Vim结合并破坏其结构，而异常结构的Vim激活自噬进而大量吞噬Vim，最终引起BTB损伤。本项目立足于课题组现有的研究基础，从Cd与Vim结合并破坏Vim的构象为研究视角，探索Cd诱导的BTB破坏中Vim表达减少的分子机制以及以自噬为靶点治疗Cd诱导的TM4细胞间连接结构破坏的效果，以期解析Cd所致的BTB破坏中Vim与自噬之间的相互调控机制和发现潜在的治疗靶点，为Cd诱导的BTB破坏的原创性研究做出贡献。

Our pre-experiment showed that the expression of vimentin in Sertoli cells was significantly decreased in the damage of blood-testis barrier (BTB) induced by cadmium (Cd), which was high related to the increased activation of autophagy. However, the regulatory mechanism of the interaction between Vimentin and autophagy is still unclear. Autophagy is crucial for maintaining the homeostasis of intracellular environment, which can remove damaged organelles, phagocytize and degrade abnormal structure proteins. We speculate that Cd may bind to Vimentin and destroy the structure of Vimentin, and Vimentin with abnormal structure activates intracellular autophagy and phagocytes Vimentin in large quantities, which eventually leads to damage of BTB. The purpose of this study is to explore the molecular mechanism of the reduction of Vimentin expression in Cd-induced BTB injury by in vitro study and animal model, and the therapeutic effect of autophagy as a target on Cd-induced junction damage between TM4 cells. We aim to disclose the molecular mechanism of the decrease of Vimentin expression in the destruction of BTB caused by Cd and discover the potential therapeutic targets, which will contribute to the original research on the destruction of BTB induced by Cd.