1,25(OH)2D3通过调控VDR/IP3R/CAMKⅡ信号通路参与病毒性心肌炎症反应的机制研究

过度炎症反应是病毒性心肌炎（VMC）病情迅速进展的重要因素，其发生机制不明。预实验发现：（1）VMC患儿血清中的促炎症因子水平与1,25(OH)2D3含量呈负相关；（2）与野生型VMC小鼠相比，1,25(OH)2D3缺乏的VMC小鼠心肌中炎性细胞浸润进一步增加，心肌细胞内Ca2+浓度及IP3R表达显著上升；（3）生物信息学分析发现，人和小鼠IP3R启动子区存在维生素D反应元件（VDRE），即1,25(OH)2D3特异性受体VDR的效用位点。因此，我们推测：1,25(OH)2D3可能通过VDR/IP3R/CaMKⅡ通路参与CVB3诱导小鼠心肌过度炎症反应。本研究基于质粒转染细胞和多种基因编辑工具鼠，运用分子生物学、生理学、病理学等手段，阐明1,25(OH)2D3通过VDR调节IP3R表达参与VMC的炎症进展。研究成果将进一步深化VMC炎症反应的理解，为VMC的防治提供新的实验依据和思路。

Excessive inflammatory response is an important factor in the rapid progression of viral myocarditis (VMC), but its formation mechanism is unknown. The results of our preliminary experiments : (1) The content of serum pro-inflammatory factors was negatively correlated with the content of 1,25(OH)2D3 in children with VMC；（2）Compared with wild-type VMC mice, 1,25(OH)2D3 deficient VMC mice showed a further increase in inflammatory cell infiltration in the myocardium as well as the concentration of Ca2+ and the expression of IP3R； (3) Bioinformatics analysis revealed the presence of vitamin D response element (VDRE) in the human and mouse IP3R promoter region, which is the utility site of the 1,25(OH)2D3 specific receptor VDR.Therefore, we speculated that 1,25(OH)2D3 may participate in CVB3-induced myocardial hyperinflammatory reactions in mice through the VDR/IP3R/CaMKⅡ pathway. Based on plasmid transfected cells and a variety of gene editing tool mice, this study will elucidate the involvement of 1,25(OH)2D3 in the inflammatory progression of VMC through VDR regulation of IP3R expression by means of molecular biology, physiology, and pathology.The research results will further deepen the understanding of the inflammatory response of VMC, and provide new experimental evidence and ideas for the prevention and treatment of VMC.