硫化氢对胃肠道的“双相”调节作用及其介导的药物效-毒转化  

Dual modulating effects of hydrogen sulfide on gastrointestinal tract and efficacy-toxicity transformation of hydrogen sulfide-mediated drugs

作　　者：于金高 李娜[1,2] 王征[1] 惠玉晶 贺宇 樊修和 YU Jingao;LI Na;WANG Zheng;HUI Yu-jing;HE Yu;FAN Xiu-he(Co-construction Collaborative Innovation Centerfor Chinese Medicine Resources Industrialization by Shaanxi&Education Ministry/State Key Laboratory of Research&Development of Characteristic Qin Medicine Resources(Cultivation)/Shaanxi Innovative Drug Research Center,Shaanxi University of Chinese Medicine,Xianyang712046,China;Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine,Shaanxi Provincial Administration of Traditional Chinese Medicine Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]陕西中医药大学陕西中药资源产业化省部共建协同创新中心/秦药特色资源研究开发国家重点实验室(培育)/陕西省创新药物研究中心,陕西咸阳712046 [2]陕西中医药大学陕西省中医药管理局中药药效机制与物质基础重点研究室,陕西咸阳712046

出　　处：《中国中药杂志》2022年第15期3986-3993,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82003964);陕西中医药大学校级科研课题(2020GP30);陕西高校青年创新团队项目。

摘　　要：硫化氢是机体细胞重要的信号转导分子之一,其在胃肠道内的合成和分解代谢极为旺盛,在胃肠道生理病理过程中的作用也十分复杂。通过梳理近年来有关硫化氢和胃肠道相关的研究文献,提出硫化氢在胃肠道内发挥着“双相”调节作用,低浓度下可促进胃肠道功能,而高浓度下则损害胃肠道。硫化氢供体药物或硫化氢代谢调节剂通过恢复硫化氢代谢稳态从而发挥治疗作用,并通过硫化氢相关的肠生物轴将药物作用范围扩大到全身组织;同时,药物可因性质不稳定、局部剂量过高、药理效应偏强等原因,使硫化氢代谢偏离稳态,从而诱发毒副作用或将治疗作用逐渐转化为毒副作用。相关认识可为硫化氢生理病理作用机制的深入研究以及硫化氢相关药物研发及其毒、效机制研究提供参考。Hydrogen sulfide is one of the most important signal transduction molecules in the body. Its anabolism and catabolism in the gastrointestinal tract(GT) are extremely high, and its role in the physiological and pathological process of the GT is fairly complicated. The study reviewed recent literature on hydrogen sulfide and GT, and proposed that hydrogen sulfide exerted dual modulating effects in the GT;specifically, it promoted the functions of the GT at low concentrations while damaged the GT at high concentrations. Hydrogen sulfide donors or metabolic modifiers exerted their therapeutic effects by restoring the metabolic homeostasis of hydrogen sulfide, and extended their efficacy to other tissues through hydrogen sulfide related gut-axis. Additionally, drugs could deviate hydrogen sulfide metabolism from the normal state due to their instability of structure, local over exposure and/or excessive pharmacological effects, thus inducing toxic and side effects or transforming therapeutic effects into toxic and side effects. This study provided references for the deep research on physiological and pathological mechanisms of hydrogen sulfide and facilitated the development of hydrogen sulfide-related drugs and discovery of their toxicity and efficacy mechanism.

关 键 词：硫化氢 代谢稳态 胃肠道 菌群 供体 毒性 效-毒转化 机制 

分 类 号：R285[医药卫生—中药学]