Norrin信号在肝纤维化血管新生中的作用和龙血素B的干预影响

Chronic liver disease cause serious health burdens in china. At present study on angiogenesis of interstitial remodeling in progressive liver fibrosis has attracted many scientists attention. Angiogenesis in liver fibrosis and the advantages and disadvantages of matrix reconstruction remains unclear. Discovered in the early effect of Dragon's blood B can inhibit pathological angiogenesis and hepatic stellate cell activation and delay the progression of liver fibrosis, but its molecular mechanisms of angiogenesis in the bi-directional effect of hemostatic and promoting blood circulation mechanism remains unclear, expression of Norrin was upgraded in actue liver injury. Norrin signals can inhibit pathological angiogenesis, maintain the construction of normal vascular network, antagonistic TGF-beta signal and play a positive role in retinal angiogenesis and proliferative diseases. Currently Norrin is not investigated in chronic liver disease. Through separation rat liver interstitial cell study the expression of Norrin signal protein in endothelial cell and hepatic stellate cells, with modify the expression of Norrin and Dragon's blood B intervention, research the effect of hepatic stellate cells activation and angiogenesis; in vivo, comparison the expression of Norrin in positioning quantitative and timing between acute liver injury and chronic liver injury, and the changes after dragon blood B intervention, the aims is investigate the effect of Norrin signal on interstitial remodeling in progressive liver fibrosis. Research will explore new targets for intervention strategies in chronic liver disease and also supply the theoretical base of anti-fibrosis effects in angiogenesis intervention in traditional Chinese medicine.

慢性肝病进展与血管新生关系密切，肝纤维化间质重建中血管新生机制和利弊关系仍不明确。Norrin信号有促进构建正常功能血管网络和抑制病理性血管新生的双向作用，在血管增殖病变中发挥正向效应。前期发现Norrin在急性肝损伤中表达上调，在慢性肝损伤中随纤维化进展表达减弱。龙血素B单体抑制病理性血管新生和肝星状细胞活化延缓肝纤维化进展，但在血管新生中的分子作用机制仍未阐明。 体外分离大鼠肝脏间质细胞，观察Norrin信号分子在窦内皮细胞和星状细胞中的表达，通过改变Norrin表达和龙血素B干预，观察其对星状细胞活化和血管新生的影响；体内，比较Norrin在慢性肝损伤进展中的定位定量和时序表达，以及龙血素干预后的变化，探讨龙血素B对肝纤维化血管新生中Norrin信号的影响。研究旨在为慢性肝病血管新生干预策略探索新的靶点，若能证实也为具有活血止血双向作用的血管新生干预中药的抗纤维化作用提供理论基础。

血管新生与慢性肝病进展关系密切，肝纤维化间质重建中血管新生机制和利弊关系仍不明确。Norrin信号有促进构建正常功能血管网络和抑制病理性血管新生的双向作用，在血管增殖病变中发挥正向效应。前期发现Norrin在急性肝损伤中表达上调，在慢性肝损伤中随纤维化进展表达减弱。龙血素B单体抑制病理性血管新生和肝星状细胞活化延缓肝纤维化进展，但在血管新生中活血止血作用的机制仍未阐明。 分离大鼠肝脏间质细胞，观察Norrin信号分子在窦内皮细胞和星状细胞中的表达，通过改变Norrin表达和龙血素B干预，观察其对星状细胞活化和血管新生的影响；体内，比较Norrin在慢性肝损伤进展中的定位定量和时序表达，以及龙血素干预后的变化，探讨龙血素B对肝纤维化血管新生中Norrin信号的影响。研究旨在为慢性肝病血管新生干预策略探索新的靶点，若能证实也为具有活血止血双向作用的血管新生干预中药的抗纤维化作用提供理论基础。