酪氨酸激酶抑制剂调控宿主抗结核作用的研究进展  

Research progress on the regulation of host anti-tuberculosis effect by tyrosine kinase inhibitors

作　　者：段淑娟 王伟[2] 逄宇 李凌 Duan Shujuan;Wang Wei;Pang Yu;Li Ling(Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics/School of Medical Technology,Guangdong Medical University,Dongguan 523000,China;Department of Bacteriology and Immunology,Beijing Key Laboratory of Drug Resistant Tuberculosis/Beijing Chest Hospital,Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China)

机构地区：[1]广东医科大学医学技术学院/广东省医学分子诊断学重点实验室,东莞523000 [2]首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所/耐药结核病研究北京市重点实验室细菌免疫室,北京101149

出　　处：《中国防痨杂志》2024年第5期584-589,共6页Chinese Journal of Antituberculosis

基　　金：国家自然科学基金(82202530)。

摘　　要：尽管现有的抗结核治疗方案在药物敏感结核病患者的治疗中取得了显著成效,但是药物毒性及耐药菌株的问题日益突出。因此,研究者们开始寻找新的药物和治疗策略,以期更好地治疗结核病。宿主导向治疗(host-directed therapy,HDT)可利用小分子化合物调节宿主的免疫反应,进而保护组织并清除病原体。HDT的主要目的是增强宿主的抗结核免疫功能,同时缩短传统抗生素治疗的时间,提高治疗效果,被视为治疗结核病的一种有前景的方法。酪氨酸激酶(protein tyrosine kinase,PTK)主要参与激活细胞信号转导,从而调节细胞生长、增殖、死亡等一系列生理生化过程。酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)是一种新型抗癌药物,在多种恶性肿瘤中可靶向过表达细胞通路,也可通过诱导自噬并激活其他信号通路发挥抗肿瘤活性。研究发现,TKI也可以在巨噬细胞中调节信号转导过程,降低胞内结核分枝杆菌的载量,具有巨大的治疗潜力。因此,TKI可作为HDT的潜在候选药物,应用于临床辅助治疗结核病。笔者将从PTK及信号转导入手,针对潜在的HDT治疗结核病的靶向药物研究进行综述,旨在为HDT疗法更好地应用于现有药物及研发新药,从而辅助治疗结核病提供参考。Although existing anti-tuberculosis treatment regimens have achieved remarkable results in the treatment of patients with drug-susceptible tuberculosis,the problems of drug toxicity and resistant strains are increasingly prominent.As a result,new drugs and treatment strategies are developed to better treat tuberculosis.Host-directed therapy(HDT)uses small molecule compounds to modulate the host’s immune response,thereby to protect tissues and eliminate pathogens.The main purpose of HDT is to enhance the host’s anti-tuberculosis immune function while shorten the duration of traditional antibiotic therapy and improve the treatment effect,which is regarded as a promising method for the treatment of tuberculosis.Tyrosine kinase(PTK)is mainly involved in activating cell signal transduction,to regulate a series of physiological and biochemical processes such as cell growth,proliferation,and death.Tyrosine kinase inhibitor(TKI)is a novel anticancer drug that can target overexpressed cellular pathways in a variety of malignant tumors,and can also exert antitumor activity by inducing autophagy and activating other signaling pathways.It has been found that TKI can also regulate the signal transduction process in macrophages and reduce the intracellular Mycobacterium tuberculosis(MTB)load,which has great therapeutic potential.Therefore,TKI can be used as potential candidates for HDT in the clinical adjuvant treatment of tuberculosis.In this paper,the potential targeted drug research for the treatment of tuberculosis by transferring PTK and signaling were reviewed,aiming to provide a reference for better application of existing drugs and the development of new drugs for the treatment of tuberculosis.

关 键 词：结核 抗结核药 宿主与病原体相互作用 蛋白酪氨酸激酶类 

分 类 号：R521[医药卫生—内科学] R392[医药卫生—临床医学]