【摘要】 目的:从分子水平探讨补肾壮筋汤延缓关节软骨退变的多靶点作用,为临床上"从本治痿"理论治疗骨关节炎做出药效学阐释。方法:利用分子对接、生物网络等计算机模拟平台,以与关节软骨退变相关的基质金属酶-1、基质金属酶-2、基质金属酶-3、基质金属酶-7、基质金属酶-8、基质金属酶-9、基质金属酶-11和基质金属酶-13为靶点,以其原配体建立活性位点,研究其与补肾壮筋汤分子集中化合物的相互作用,构建延缓关节软骨退变的补肾壮筋汤分子集化合物-靶点作用网络,分析补肾壮筋汤的作用特点。结果:从补肾壮筋汤分子集中虚拟筛选出106个潜在的活性化合物,主要为苷类化合物,其中,能作用1个靶点、2个靶点和>2个靶点的化合物数目分别为33、40和33。所构建的化合物-靶点作用网络中,每个化合物的平均靶点数为2.3个,平均每个靶点与13.2个化合物相关联,且大部分化合物只能作用于少数的靶点,仅有3个化合物最多能作用于7个靶点。其化合物-靶点的作用关系曲线遵循幂函数p（k）=k^-1.6429规律,体现补肾壮筋汤中化合物与靶点的作用具有"一对多,多对一"的非线性特点。结论:补肾壮筋汤延缓关节软骨退变存在多靶导向作用,主要是通过类似混杂药物的方式起到多靶作用。这为"从本治痿"理论治疗骨关节炎提供了解释,也为从补肾壮筋汤中寻找治疗骨关节炎的新型药物提供参考与借鉴。更多还原

【Abstract】 Objective:To explore the multi-target effects of Bushen Zhuangjin decoction（BSZJD） in delaying cataplasia of articular cartilage from the molecular level, and give a pharmacodynamic illustration for the theory of "treatment for flaccidity aims at the origin". Methods:Based on the simulation platforms of molecular docking and biological network, the targets of cataplasia of articular cartilage including matrix metalloproteinase（MMP）-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-11 and MMP-13 were chosen as subject, their active-sites were built by respectively original ligand. The interaction between targets and compounds in BSZJD was studied by molecular docking. BSZJD compound-target network of delaying cataplasia of articular cartilage was constructed. The functional characteristic of BSZJD was studied by biological network. Results:Total of potential active compounds was 106, which mainly belong to saponins, and 33 compounds among them had good interaction with one target, while 40 and 33 compounds had good interaction with two targets and more than two targets, respectively. The average number of targets was 2.3 in each compound contained in compound-target network model, and every target was related to 13.2 compounds on average. Moreover, the majority of compounds acted on few targets, while three compounds acted on a large number of targets, up to a maximum of seven. The relations between BSZJD compounds and targets followed the power function p（k）=k^-1.6429, which revealed the interaction between BSZJD compounds and targets existed the nonlinear regulation pattern of "one to many, many to one". Conclusion:BSZJD effects for delaying cataplasia of articular cartilage exist multi-target effects. Furthermore, the compounds in BSZJD work mainly by ways of promiscuous drug in the therapy of OA. This comes up an explanation about BSZJD therapeutical effect for OA based on the theory of "treatment for flaccidity aims at the origin". The results also provide a certain reference and inspiration for discovering new drugs from BSZJD for treatment of OA.更多还原