清肺排毒汤、化湿败毒方和宣肺败毒方体外抗补体活化作用的比较研究

Comparison of the in vitro Effects of Qingfei Paidu Decoction(清肺排毒汤),Huashi Baidu Decoction(化湿败毒方)and Xuanfei Baidu Decoction(宣肺败毒方)against Complement Activation

目的:平行比较新冠肺炎“抗疫三方”(清肺排毒汤、化湿败毒方和宣肺败毒方)对抗新冠肺炎(COVID-19)重要病机补体活化的作用。方法:基于酶联免疫吸附测定(ELISA)原理,采用免疫球蛋白M(IgM)、酵母多糖和甘露聚糖作为包被物分别启动经典途径、替代途径和凝集素途径,通过测定补体活化终端产物攻膜复合物(C5b-9)水平以评价补体活化程度。不仅如此,通过包被新冠病毒刺突蛋白(S蛋白)与核衣壳蛋白(N蛋白)还可考察“三方”对抗这两种蛋白引起补体活化的作用。结果:“三方”均能剂量依赖地对抗经典途径、替代途径和凝集素途径引起的C5b-9生成,也均对S蛋白与N蛋白引起的C5b-9生成具有抑制作用,其中宣肺败毒方的作用最强。结论:“三方”均可在体外对抗三条补体途径的激活并抑制新冠S蛋白与N蛋白引起的补体活化,此作用可能是三方发挥治疗COVID-19作用的药效学基础之一。

Objective:To compare the effects of three decoctions for COVID-19,Qingfei Paidu Decoction(清肺排毒汤,QF),Huashi Baidu Decoction(化湿败毒方,HS),Xuanfei Baidu Decoction(宣肺败毒方,XF) against the complement activation(the important pathogenesis of COVID-19),by using the parallel experimental models. Methods:Based on the principle of ELISA,the IgM,zymosan and mannan were selected as coating substances to activate the classical, alternative and lectin complement pathway, respectively. Complement activation was evaluated by measuring the level of terminal complement complex C5b-9. Meanwhile, coated SARS-CoV-2 spike protein(S protein) and SARS-CoV-2 nucleocapsid(N protein) was employed to investigate the effects of three decoctions against complement activation mediated by these two proteins. Results:Three decoctions for COVID-19 could concentration-dependently inhibit the production of C5b-9 in three complement activation pathways, and they all inhibited the C5b-9 production triggered by S and N proteins. Among them, XF exhibited the strongest ability. Conclusion:Three decoctions for COVID-19 can suppress the complement activation mediated by all three pathways, as well as S and N proteins in vitro,suggesting that the ability of three decoctions against complement activation may be one of the pharmacodynamic bases for their clinical use in the treatment of COVID-19.