Ang-2/BMP-4信号环路在椎间盘退变中的作用机制及独活寄生汤的干预作用研究

椎间盘退变（IDD）导致的下腰痛给社会带来沉重负担。申请人前期研究发现Ang-2和BMP-4分别是促进椎间盘退变与修复的关键分子；独活寄生汤通过调控髓核细胞外基质代谢及细胞凋亡促进椎间盘修复，进一步研究证实Ang-2、BMP-4是独活寄生汤治疗IDD的核心靶点，但Ang-2、BMP-4在IDD中是否存在动态平衡及独活寄生汤的干预作用至今未见报道。本项目预实验表明IDD中Ang-2与BMP-4表达水平呈负相关且两者可相互调控，据此推测Ang-2/BMP-4通路间相互作用，构成信号调节环路，共同参与IDD的发生、发展及独活寄生汤通过恢复Ang-2/BMP-4信号环路平衡延缓IDD进程。本项目拟通过临床标本、细胞实验、动物模型，明确Ang-2/BMP-4信号环路参与IDD的作用机制及独活寄生汤干预作用，以期为阐明IDD精确病理机制提供新的实验依据，并为中医药有效治疗IDD提供新的靶点。

Low back pain caused by intervertebral disc degeneration (IDD) raises great concern in the society. The results of previous study by the applicant show that Ang-2 and BMP-4 are the key molecules to disc degeneration and repair, respectively. The drug of duhuo jisheng decoction can improve disc repair by regulating extracellular matrix metabolism and cell apoptosis. Results of more studies show that Ang-2 and BMP-4 are the core targets for using this drug for treatment of IDD. However, whether Ang-2 and BMP-4 has dynamic equilibrium in IDD and the inhibition of this drug has not been reported. The preliminary experiment shows that there is a negative correlation between the expression level of Ang-2 and BMP-4 in IDD, and the two can regulate each other. Based on this, we surmise that Ang-2/BMP-4 signaling pathways interact with each other to form a signaling regulatory loop to participate in the occurrence and development of IDD and duhuo jisheng decoction can interfere with and delay the IDD process by restoring the equilibrium of Ang-2/BMP-4 signaling loop. Through clinical specimens, cell experiments and animal models, this program aims to clarify the mechanism of Ang-2/BMP-4 signaling loop in IDD and the inhibition of duhuo jisheng decoction, so as to provide new experimental basis for the pathological mechanism of IDD and new target for Chinese medicine to treat IDD effectively.