DMP1在HFRS发病机制中的作用及机理研究

DMP1 is a kind of collagen acidic extracellular matrix protein, which is initially identified in bone and teeth. Recent studies have shown that DMP1 was widely expressed in the body, including vascular endothelial cells and kidney tissues. DMP1 was reported as one of the structural proteins to maintain the integrity of endothelial cells by down-regulating the phosphorylation of VEGFR2 mediated by VEGF and inducing the expression of VE-cadherin. Therefore, DMP1 is likely to be one of the most important cellular structural proteins to maintain the permeability of vascular endothelial cells. In this study, we determined to research the expression of DMP1 in patients with HFRS and clarify the correlation between DMP1 and related inflammatory factors. Meanwhile, the inhibitory effect of exogenous DMP1 on decreasing the hyperpermeability of vascular endothelial cell infected by HTNV, VEGF and other inflammation factors, which might provide theoretical basis for the pathogenesis of HFRS and new clues for clinical treatment of HFRS. As the infection of HTNV has been widely concerned as a heavy burden on Chinese, this research has potential application value and theoretical significance in clinical therapy for HFRS.

HFRS患者的基本病变是血管内皮细胞的通透性增加，DMP1是骨组织以及牙本质表达的非胶原性酸性细胞外基质蛋白，近期发现DMP1在体内表达广泛，在血管内皮细胞及肾脏组织中均可见，有研究提示DMP1具有抑制VEGFR2磷酸化的功能，并且通过诱导钙粘蛋白的表达，抑制VEGF介导的下调钙粘蛋白的作用，从而稳定血管内皮细胞的通透性。因此DMP1可能是具有稳定血管内皮细胞通透性的细胞结构蛋白。本课题以DMP1为研究对象，观察HFRS患者DMP1的表达规律以及与疾病相关性，研究VEGF及相关炎症因子对DMP1的作用及影响，同时研究外源性DMP1对HTNV和VEGF等炎症因子引起的血管内皮细胞通透性增高的影响及作用机理，为进一步探讨HFRS的发病机制提供理论依据，进而为临床治疗HFRS提供新思路。由于HFRS在中国人群中疾病负担较重，所以本研究对HFRS的临床治疗有潜在的应用价值和理论意义。