基于中药系统毒理学数据库的生育毒性中药特性及机制研究

Study on characteristics and mechanism of Chinese herbs with fertility toxicity based on Traditional Chinese Medicine System Toxicology Database

目的探讨生育毒性中药的特点及作用机制。方法检索中药系统毒理学数据库(TCMSTD)中具有生殖毒性、发育毒性和遗传毒性的中药材,收集其药性、药味、归经、毒性分类、临床表现、毒性成分和作用靶点,进行描述性统计分析。结果筛选出具有生育毒性的中药材共55种,其药性属温性[20种(36.4%)]和寒性[15种(27.3%)]居多,药味以苦、辛占比较高[苦-辛、苦和辛味分别占30.9%(17种)、23.6%(13种)和18.2%(10种)],归经多为肝、肺、脾和肾[分别占58.2%(32种)、38.2%(21种)、38.2%(21种)和34.5%(19种)],其生育毒性的表现主要为男性或女性生殖机能损伤、胚胎生长发育异常和遗传/细胞毒性,其结果可能导致怀孕率降低、流产、胎儿生长发育异常等。有已知生育毒性成分的中药材共29种,涉及35种毒性成分。其中30种毒性成分已知毒性靶点,涉及11个靶点。较常见的毒性靶点包括甲状腺激素受体β、细胞色素P4501A1、性激素结合球蛋白和白细胞介素1β。结论生育毒性中药的药性多属温性和寒性,药味多苦、辛,归经多为肝、肺、脾和肾经,主要通过改变机体内分泌、干扰性激素代谢等途径影响生育能力和胚胎发育。

Objective To explore the characteristics and mechanism of Chinese herbs with fertility toxicity.Methods Chinese herbs with reproductive toxicity,developmental toxicity and genetic toxicity were retrieved from Traditional Chinese Medicine System Toxicology Database.The property,taste,meridian tropism,toxicity classification and performance,and the toxic component and action target of each medicinal material were collected and descriptive statistical analysis was performed.Results A total of 55 kinds of Chinese herbs with fertility toxicity were screened out.They were mostly warm[20(36.4%)]or cold[15(27.3%)]in property,and mostly bitter and pungent in taste[bitter‑pungent,bitter,and pungent accounted for 30.9%(17/55),23.6%(13/55)and 18.2%(10/55)].The channel tropisms were mainly liver,lung,spleen,and kidney[58.2%(32/55),38.2%(21/55),38.2%(21/55)and 34.5%(19/55)],and the main manifestations of its reproductive toxicity were reproductive function damage in males and females,abnormal embryonic growth and development and genetic/cytotoxicity,which might lead to reduced pregnancy rate,miscarriage,abnormal fetal growth and development,etc.There were 29 kinds of Chinese herbs with 35 known fertility toxic components.Among them,30 toxic components had 11 known toxic targets.The more common toxic targets included thyroid hormone receptor beta,cytochrome P4501A1,sex hormone‑binding globulin and interleukin‑1 beta.Conclusions Chinese herbs with fertility toxicity are mostly warm or kidney;they mainly affect fertility and embryonic development by changing the body′s endocrine and interfering with sex hormone metabolism.