黄连解毒丸治疗“ 实热火毒” 证候临床生物标志物辨识验证研究  

Identification and validation of clinical biomarkers for the treatment of excess heat causing fire toxins syndrome with Huanglian Jiedu Pill

作　　者：罗珂珂 王宏洁[1] 王梦晓 田孟尧 司南[1] 夏文 陈运琴 杨健[1] 李星 覃广源 周严严[1] 边宝林[1] LUO Ke-ke;WANG Hong-jie;WANG Meng-xiao;TIAN Meng-yao;SI Nan;XIA Wen;CHEN Yun-qin;YANG Jian;LI Xing;QIN Guang-yuan;ZHOU Yan-yan;BIAN Bao-lin(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Guizhou Bailing Group Pharmaceutical Co.,Ltd.,Anshun 561000,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]贵州百灵企业集团制药股份有限公司,贵州安顺561000

出　　处：《时珍国医国药》2025年第1期176-183,共8页Lishizhen Medicine and Materia Medica Research

基　　金：中国中医科学院科技创新工程重大攻关项目(CI2021A04507);中国中医科学院基本科研业务费优秀青年科技人才培养专项-创新类(ZZ15-YQ-038);中国中医科学院中药研究所启航人才项目和国自然培育项目(ZXKT22037,ZXKT22008)。

摘　　要：目的课题组通过招募57例发现集受试者初步探索和筛选了黄连解毒丸干预“实热火毒”证候的临床生物标志物,但结果仍需进一步辨识验证。方法招募30例“实热火毒”证候受试患者,以黄连解毒丸为受试药物,收集其给药前后的血液样本,并招募30例健康人群作为正常对照组。采用液相芯片技术,酶联免疫方法,靶向脂质组学及靶向测定三羧酸循环中间体技术验证课题组前期找到的与“实热火毒”证候密切相关的炎症,氧化应激,能量代谢及脂质成分。结果LDH,TNF-α,IL-8,IL-6,PC(16∶1/18∶2),PC(18∶2/20∶4),PC(16∶0/16∶1),琥珀酸,乳酸,苹果酸,α-酮戊二酸,富马酸,一磷酸腺苷,葡萄糖在正常对照组,黄连解毒丸组,及“实热火毒”证候三组之间均表现出显著差异,可以作为黄连解毒丸干预“实热火毒”证候的潜在生物标志物群。结论该研究为Ⅱ期及Ⅲ期临床深入探索黄连解毒丸治疗“实热火毒”证候机制奠定基础,为证候类新药研发及其创新作用机制研究提供范式。Objective To conduct initial exploration and screening of clinical biomarkers for treating excess heat causing fire toxins syndrome with Huanglian Jiedu Pill(HJP)using 57 cases in the preliminary phase.However,further identification and validation of the results are still needed.Methods The study recruited 30 participants with confirmed excess heat causing fire toxins syndrome.HJP was used as the investigational drug.Blood samples were collected before and after administration,and another 30 healthy individuals were recruited as the normal control group.Liquichip technology,enzyme-linked immunosorbent assay,targeted lipidomics,and targeted determination of tricarboxylic acid cycle intermediates were used to validate the inflammation,oxidative stress,energy metabolism,and lipid components that were closely related to excess heat causing fire toxins syndrome as identified by the research group.Results LDH,TNF-α,IL-8,IL-6,PC(16∶1/18∶2),PC(18∶2/20∶4),PC(16∶0/16∶1),succinate,lactate,malic acid,Oxaglutaric acid,fumaric acid,adenosine monophosphate,and glucose showed significant differences among the three groups.These biomarkers can be potentially used to intervene the excess heat causing fire toxins syndrome with HJP.Conclusion This study lays a foundation for exploring the mechanism of HJP in treating excess heat causing fire toxins syndrome in phase II and III clinical trials,and provides a paradigm for the development of new drugs and the study of innovative mechanisms in syndrome-oriented treatments.

关 键 词：黄连解毒丸 “实热火毒”证候 炎症-氧化应激-能量代谢 脂质组学 三羧酸循环 

分 类 号：R2-03[医药卫生—中医学]