基于2种复杂网络分析方法探索活血化瘀类中药注射液治疗急性脑梗死的疗效

Exploring efficacy of Chinese medicine injection for promoting blood circulation and removing blood stasis in treatment of acute cerebral infarction based on two complex network analysis methods

该研究基于2种复杂网络分析方法,从临床用药和作用机制2个角度探索活血化瘀类中药注射液治疗急性脑梗死的疗效。首先,运用网状Meta分析方法,获得2019年版《国家基本医疗保险、工伤保险和生育保险药品目录》中13种中药注射液治疗急性脑梗死的疗效排序;其次,运用网络药理学研究方法,从核心靶点和网络功能富集2个层面探讨疗效排序相对靠前的2种中药注射液治疗急性脑梗死作用机制的异同。网状Meta分析结果显示,在神经功能缺损评分总有效率和NIHSS评分疗效排序上,脉络宁注射液均优于丹红注射液。网络药理学结果显示,脉络宁注射液治疗脑梗死的核心靶点、相互作用网络和富集的生物功能、信号通路数量多于丹红注射液。2种中药注射液均可通过TP53、NOS3等核心靶点,纤维蛋白溶解、一氧化氮生物合成过程、一氧化氮介导的信号转导、内皮细胞的细胞凋亡负调节、凋亡过程的负调控等生物过程,PI3K-Akt、HIF-1信号通路和细胞凋亡等信号通路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药物临床疗效的差异。中医药疗效评价倡导以疗效为先导的研究策略,先进行临床疗效比较研究,再选择临床疗效突出的药物开展机制研究,可更好地为临床中相同疾病同类竞争药物的选择提供参考和依据。

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.