VEGF下调Calmodulin维持肝窦内皮细胞窗孔结构在肝纤维化中的作用及机制

研究肝纤维化对于治疗慢性肝病具有重要意义。肝窦内皮细胞（liver sinusoidal endothelial cell，LSEC）窗孔结构的消失是激活肝星状细胞，引发肝纤维化的前提条件。已有的报道及课题组前期实验均证实VEGF具有维持LSEC窗孔结构的作用，然而其作用机制仍未阐明。我们前期研究发现，钙调蛋白（Calmodulin，CaM）在LSEC窗孔结构消失过程中表达显著上升，而加入VEGF后，其上升受到抑制。由此可以推测，VEGF很有可能通过下调CaM维持LSEC的窗孔结构从而抑制肝纤维化的发生。本课题拟通过研究VEGF下调LSEC中CaM的具体类型及途径，证实VEGF维持LSEC窗孔结构与下调CaM有关，并通过干预CaM的表达深入分析其对VEGF维持窗孔结构的影响，阐明VEGF通过下调CaM维持LSEC窗孔结构的具体作用机制，从而为临床对肝纤维化的治疗提供新的思路及解决策略。

To research liver fibrosis is very important for clinical therapy of chronic liver disease. The defenestration of liver sinusoidal endothelial cells (LSEC) is the prerequisite for activation of hepatic stellate cells and the occurrence of liver fibrosis. According to the previous report and the results of our lab, VEGF is confirmed for maintaining the fenestrae of LSEC. However, the mechanism is still unknown. In prophase research, we found that the expression of calmodulin(CaM) in LSEC increased when the fenestrae was disappearing and this trend could be suppressed after adding VEGF in. So it can be concluded that VEGF sustains LSEC fenestrae through down-regulating the expression of CaM. This project intends to proof the functional relationship between VEGF and CaM by detecting the categorical changes of CaM and possible pathways that mediated by VEGF. Then further analyzes the effect of CaM on VEGF about sustaining LSEC fenestraeand through regulating CaM expression and elucidate the mechanism, which may provide new ideas and solutions for clinical treatment of liver fibrosis.