Hu Rui-Xue, Yu Dan-Dan, Li Hui-Min, Gu Hao, Zhao Hui, Xu Hai-Yu, Li Bing, Hu Jing, Liao Xing
Center for Evidence-based Chinese Medicine,Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences Beijing 100700,China.
Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences Beijing 100700,China.
Zhongguo Zhong Yao Za Zhi. 2021 Jul;46(14):3722-3731. doi: 10.19540/j.cnki.cjcmm.20201209.501.
This study aims to explore the efficacy of Chinese medicine injections( CMIs) for promoting blood circulation and removing blood stasis for acute cerebral infarction from the perspectives of clinical medication and mechanism of action based on two complex network analysis methods. Firstly,the current 13 kinds of CMIs for acute cerebral infarction were obtained from 2019 List of medicines for national basic medical insurance,industrial injury insurance and maternity insurance with the method of network Meta-analysis. Secondly,with the use of network pharmacology,the mechanisms of top 2 CMIs with the highest therapeutic effect for acute cerebral infarction were explored from two levels including core target and network function enrichment. The result of network Meta-analysis showed Mailuoning Injection was superior to Danhong Injection in terms of total effectiveness rate for neurological deficit score and NIHSS score. The network pharmacology results showed that Mailuoning Injection had more core targets,interaction networks,enriched biological functions and more signaling pathways than Danhong Injection for cerebral infarction. Both two CMIs can play a role in treating cerebral infarction through core targets such as TP53 and NOS3,biological processes such as fibrinolysis,nitric oxide biosynthesis,nitric oxide-mediated signal transduction,negative regulation of apoptosis in endothelial cells and apoptosis process,as well as the signaling pathways such as PI3 K-Akt signaling pathway,HIF-1 signaling pathway and cell apoptosis signaling pathways. The results of pharmacological studies explained their differences in clinical efficacy to a certain extent. A research strategy based on curative effect should be advocated in efficacy evaluation of traditional Chinese medicine,where comparative research on clinical efficacy can be conducted firstly,and then mechanism research based on outstanding effective drugs to better provide references and basis for selection of similar competitive drugs for one disease in the clinical practice.
本研究旨在基于两种复杂网络分析方法，从临床用药和作用机制的角度探讨活血化瘀类中药注射剂治疗急性脑梗死的疗效。首先，采用网状Meta分析方法，从《2019年国家基本医疗保险、工伤保险和生育保险药品目录》中获取目前治疗急性脑梗死的13种中药注射剂。其次，运用网络药理学方法，从核心靶点和网络功能富集两个层面，探讨治疗急性脑梗死疗效最佳的前2种中药注射剂的作用机制。网状Meta分析结果显示，在神经功能缺损评分及美国国立卫生研究院卒中量表（NIHSS）评分的总有效率方面，脉络宁注射液优于丹红注射液。网络药理学结果表明，脉络宁注射液较丹红注射液在脑梗死方面具有更多的核心靶点、相互作用网络、富集的生物学功能及更多的信号通路。两种中药注射剂均可通过TP53和NOS3等核心靶点、纤维蛋白溶解、一氧化氮生物合成、一氧化氮介导的信号转导、内皮细胞凋亡的负调控及凋亡过程等生物学过程，以及PI3K-Akt信号通路、HIF-1信号通路和细胞凋亡信号通路等发挥治疗脑梗死的作用。药理学研究结果在一定程度上解释了它们临床疗效的差异。在中药疗效评价中应倡导基于疗效的研究策略，即先进行临床疗效的对比研究，再基于疗效突出的药物进行作用机制研究，以便更好地为临床实践中针对某一疾病选择同类竞争性药物提供参考和依据。
