鞘氨醇-1-磷酸及其受体在结核分枝杆菌感染和抗生素研发中的作用  

The roles of sphingosine-1-phosphate and its receptor in Mycobacterium tuberculosis infection and novel antibiotics discovery

作　　者：甄俊峰 鄢双全 李雨竹 谢建平[1] ZHEN Jun-feng;YAN Shuang-quan;LI Yu-zhu;XIE Jian-ping(Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource ofthe Three Gorges Area, School of Life Sciences, Southwest University, Chongqing 400715, China)

机构地区：[1]西南大学生命科学学院现代生物医药研究所三峡库区生态环境与生物资源省部共建国家重点实验室培育基地

出　　处：《药学学报》2019年第8期1348-1355,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81871182,81371851)

摘　　要：结核病仍是全球关注的重大公共卫生问题,这与其耐药及感染后的持留和免疫逃逸有关。鞘脂类生物活性分子参与多个重要的病理生理过程。鞘氨醇-1-磷酸是鞘脂类代谢的关键产物,能够通过自分泌/旁分泌的方式发挥作用。鞘氨醇-1-磷酸调节T细胞和结核分枝杆菌感染过程中多种抗原呈递细胞,促进单核细胞抗原的加工和表达,促进吞噬溶酶体的成熟,还可以调控Ca2+稳态以及参与巨噬细胞自噬等过程,抑制结核分枝杆菌在宿主细胞内的存活和生长,有效降低结核菌感染小鼠肺的损伤。外源添加鞘氨醇-1-磷酸,能够减少结核分枝杆菌感染小鼠肺和脾的分枝杆菌量。本文综述了鞘氨醇-1-磷酸及其受体调控网络,阐述了鞘氨醇-1-磷酸在抑制结核分枝杆菌感染宿主细胞后存活过程的具体机制,旨在为结核病治疗寻找新的防控靶标。Tuberculosis(TB) caused by Mycobacterium tuberculosis(M. tuberculosis) infection remains a major public health problem of global concern, largely due to antibiotics resistance, persistence and immune evasion.Sphingolipid bioactive molecules are involved in several important pathophysiological processes. Sphingosine-1-phosphate is a key product of sphingolipid metabolism, and can play a role in two manners: autocrine and/or paracrine. Sphingosine-1-phosphate regulates T cells and a variety of antigen-presenting cells during M. tuberculosis infection, promotes antigen processing and expression in monocytes, is involved in the maturation of phagolysosome,regulates Ca2+ homeostasis, participates in the autophagy of macrophages, inhibits the survival and proliferation of M. tuberculosis within host cells, and effectively reduces the necrosis of the mouse lungs infected by M. tuberculosis.Injection of 20 nmol per mouse sphingosine-1-phosphate inhibited up to 47% of mycobacterial growth in the lung and spleen of mice infected by M. tuberculosis. In this paper, sphingosine-1-phosphate, its receptors and regulatory network were reviewed, and the specific mechanism of sphingosine-1-phosphate inhibiting the survival of M. tuber‐culosis-infected host cells was elaborated. This will provide novel insights into the new targets for tuberculosis prevention and treatment.

关 键 词：结核分枝杆菌 鞘氨醇-1-磷酸 抗原加工 调控机制 结核病 耐药 

分 类 号：R966[医药卫生—药理学]