自噬与结核病相关性的研究进展

doi:10.3969/j.issn.1004-583X.2024.10.015

摘要/Abstract

摘要：

结核病是结核分枝杆菌(mycobacterium tuberculosis, MTB)感染机体导致的慢性传染性疾病。结核病的发病与宿主免疫状态密切相关。自噬(autophagy)是真核生物一种高度保守的保护性机制,对维持细胞稳态具有重作用。越来越多的证据表明自噬参与了结核病的发生发展,自噬相关基因的多态性与结核病易感性密切相关。自噬有助于机体限制MTB的存活,然而MTB又可以通过多种机制免疫逃避自噬。同时,基于自噬机制的宿主导向治疗(host directed therapy, HDT)在抗结核治疗中表现出乐观的前景。本文就近年自噬在结核病中的研究作一综述,以期从自噬角度为结核病的防治提供新参考。

关键词: 自噬, 结核分枝杆菌, 发病机制, 宿主导向治疗

中图分类号:

R378.911

王鹏, 余玲, 李果, 庞敏, 胥力川, 张全波. 自噬与结核病相关性的研究进展[J]. 临床荟萃, 2024, 39(10): 953-968.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.10.015

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I10/953

图/表 2

参考文献 91

[1]	世界卫生组织. 2023年全球结核病报告[EB/OL]. [2023.11.06]. https://www.who.int/zh/news-room/fact-sheets/detail/tuberculosis.
[2]	吴雪琼, 范琳. 活动性结核病患者免疫功能状态评估和免疫治疗专家共识(2021年版)[J]. 中国防痨杂志, 2022, 44(1): 9-27.
[3]	张西燕, 付玉荣, 伊正君. 自噬在巨噬细胞抗结核感染中的作用及调控机制研究进展[J]. 中国病原生物学杂志, 2018, 13(7): 789-792, 799.
[4]	赵润鹏, 吴静, 胡东. 结核分枝杆菌感染的巨噬细胞的死亡和自噬[J]. 细胞与分子免疫学杂志, 2016, 32(12): 1711-1714.
[5]	Klionsky DJ, Petroni G, Amaravadi RK, et al. Autophagy in major human diseases[J]. EMBO J, 2021, 40(19): e108863.
[6]	Deretic V. Autophagy in inflammation, infection, and immunometabolism[J]. Immunity, 2021, 54(3): 437-453. doi: 10.1016/j.immuni.2021.01.018 pmid: 33691134
[7]	杜金艳, 王燕, 张燕, 等. 结核感染患者外周血中性粒细胞自噬水平的研究[J]. 国际检验医学杂志, 2019, 40(3): 334-337.
[8]	Yu Q, Zhu X, Di W, et al. High beclin-1 expression in human alveolar macrophage significantly correlate with the bacteriologic sterilization in pulmonary tuberculosis patients[J]. Clin Lab, 2016, 62(6): 1003-1007. pmid: 27468561
[9]	郭亚南, 梁国标, 陈安健, 等. 自噬相关因子在结核肾组织中的表达及意义[J]. 贵州医药, 2019, 43(6): 850-853.
[10]	费劲萌, 刘红艳. 活动性肺结核患者血清NOD2、ATG16L1水平与病情及预后的关系研究[J]. 传染病信息, 2023, 36(2): 163-167.
[11]	张先言. 活动性肺结核病患者循环单核细胞噬菌能力和自噬水平研究[D]. 广东: 汕头大学, 2020.
[12]	Pellegrini JM, Sabbione F, Morelli MP, et al. Neutrophil autophagy during human active tuberculosis is modulated by SLAMF1[J]. Autophagy, 2021, 17(9): 2629-2638.
[13]	李颖, 黄秦, 陈维贤, 等. 自噬相关基因频率分布特征与肺结核相关性研究[J]. 重庆医学, 2017, 46(22): 3046-3049.
[14]	Zhang RR, Liang L, Chen WW, et al. ULK1 polymorphisms confer susceptibility to pulmonary tuberculosis in a Chinese population[J]. Int J Tuberc Lung Dis, 2019, 23(2): 265-271. doi: 10.5588/ijtld.18.0174 pmid: 30808462
[15]	Cheng S, Sun C, Lao W, et al. Association of VAMP8 rs1010 Polymorphism with Host Susceptibility to Pulmonary Tuberculosis in a Chinese Han Population[J]. Genet Test Mol Biomarkers, 2019, 23(5): 299-303.
[16]	Ajayi T, Rai P, Shi M, et al. Race-specific association of an IRGM risk allele with cytokine expression in human subjects[J]. Sci Rep, 2023, 13(1): 12911. doi: 10.1038/s41598-023-40313-3 pmid: 37558924
[17]	Zafar A, Shafiq M, Ali B, et al. Association of IRGM promoter region polymorphisms and haplotype with pulmonary tuberculosis in Pakistani (Punjab) population[J]. Tuberculosis (Edinb), 2022, 136: 102233.
[18]	Yuan L, Ke Z, Ma J, et al. IRGM gene polymorphisms and haplotypes associate with susceptibility of pulmonary tuberculosis in Chinese Hubei Han population[J]. Tuberculosis (Edinb), 2016, 96: 58-64.
[19]	Xie H, Li C, Zhang M, et al. Association between IRGM polymorphisms and tuberculosis risk: A meta-analysis[J]. Medicine (Baltimore), 2017, 96(43): e8189.
[20]	Lu Y, Li Q, Peng J, et al. Association of autophagy-related IRGM polymorphisms with latent versus active tuberculosis infection in a Chinese population[J]. Tuberculosis (Edinb), 2016, 97: 47-51.
[21]	Yang CS, Kim JJ, Lee HM, et al. The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy[J]. Autophagy, 2014, 10(5): 785-802.
[22]	Dwivedi R, Baindara P. Differential regulation of TFEB-induced autophagy during mtb infection and starvation[J]. Microorganisms, 2023, 11(12):2944.
[23]	Wu X, Zhang J, Ma C, et al. A role for Wnt/beta-catenin signalling in suppressing Bacillus Calmette-Guerin-induced macrophage autophagy[J]. Microb Pathog, 2019, 127: 277-287.
[24]	Lunemann JD, Munz C. Autophagy in CD4+ T-cell immunity and tolerance[J]. Cell Death Differ, 2009, 16(1): 79-86. doi: 10.1038/cdd.2008.113 pmid: 18636073
[25]	Khan N, Vidyarthi A, Pahari S, et al. Signaling through NOD-2 and TLR-4 Bolsters the T cell Priming Capability of Dendritic cells by Inducing Autophagy[J]. Sci Rep, 2016, 6: 19084. doi: 10.1038/srep19084 pmid: 26754352
[26]	Feng S, Mcnehlan ME, Kinsella RL, et al. Autophagy promotes efficient T cell responses to restrict high-dose mycobacterium tuberculosis infection in mice[J]. Nat Microbiol, 2024, 9(3): 684-697.
[27]	Kinsella RL, Kimmey JM, Smirnov A, et al. Autophagy prevents early proinflammatory responses and neutrophil recruitment during mycobacterium tuberculosis infection without affecting pathogen burden in macrophages[J]. PLoS Biol, 2023, 21(6): e3002159.
[28]	Castillo EF, Dekonenko A, Arko-Mensah J, et al. Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation[J]. Proc Natl Acad Sci U S A, 2012, 109(46): E3168-E3176.
[29]	Golovkine GR, Roberts AW, Morrison HM, et al. Autophagy restricts mycobacterium tuberculosis during acute infection in mice[J]. Nat Microbiol, 2023, 8(5): 819-832. doi: 10.1038/s41564-023-01354-6 pmid: 37037941
[30]	Liu K, Hong D, Zhang F, et al. MicroRNA-106a inhibits autophagy process and antimicrobial responses by targeting ULK1, ATG7, and ATG16L1 during mycobacterial infection[J]. Front Immunol, 2020, 11: 610021.
[31]	Guo L, Zhao J, Qu Y, et al. MicroRNA-20a inhibits autophagic process by targeting ATG7 and ATG16L1 and favors mycobacterial survival in macrophage cells[J]. Front Cell Infect Microbiol, 2016, 6: 134.
[32]	Guo L, Zhou L, Gao Q, et al. MicroRNA-144-3p inhibits autophagy activation and enhances Bacillus Calmette-Guerin infection by targeting ATG4a in RAW264.7 macrophage cells[J]. PLoS One, 2017, 12(6): e179772.
[33]	Qu Y, Ding S, Ma Z, et al. MiR-129-3p favors intracellular BCG survival in RAW264.7 cells by inhibiting autophagy via Atg4b[J]. Cell Immunol, 2019, 337: 22-32. doi: S0008-8749(18)30454-4 pmid: 30782398
[34]	Qu Y, Jiang D, Liu M, et al. LncRNA DANCR restrained the survival of mycobacterium tuberculosis H37Ra by sponging miR-1301-3p/miR-5194[J]. Front Microbiol, 2023, 14: 1119629.
[35]	Jiang F, Lou J, Zheng XM, et al. LncRNA MIAT regulates autophagy and apoptosis of macrophage infected by mycobacterium tuberculosis through the miR-665/ULK1 signaling axis[J]. Mol Immunol, 2021, 139: 42-49. doi: 10.1016/j.molimm.2021.07.023 pmid: 34454184
[36]	Ke Z, Lu J, Zhu J, et al. Down-regulation of lincRNA-EPS regulates apoptosis and autophagy in BCG-infected RAW264.7 macrophages via JNK/MAPK signaling pathway[J]. Infect Genet Evol, 2020, 77: 104077.
[37]	Luo HL, Pi J, Zhang JA, et al. Circular RNA TRAPPC6B inhibits intracellular mycobacterium tuberculosis growth while inducing autophagy in macrophages by targeting microRNA-874-3p[J]. Clin Transl Immunology, 2021, 10(2): e1254.
[38]	Wu M, Liu Z, Zhang S. Down-regulation of hsa_circ_0045474 induces macrophage autophagy in tuberculosis via miR-582-5p/TNKS2 axis[J]. Innate Immun, 2022, 28(1): 11-18.
[39]	Alvarez-Jimenez VD, Leyva-Paredes K, Garcia-Martinez M, et al. Extracellular vesicles released from mycobacterium tuberculosis-infected neutrophils promote macrophage autophagy and decrease intracellular mycobacterial survival[J]. Front Immunol, 2018, 9: 272. doi: 10.3389/fimmu.2018.00272 pmid: 29520273
[40]	Garcia-Martinez M, Vazquez-Flores L, Alvarez-Jimenez VD, et al. Extracellular vesicles released by J774A.1 macrophages reduce the bacterial load in macrophages and in an experimental mouse model of tuberculosis[J]. Int J Nanomedicine, 2019, 14: 6707-6719.
[41]	Cheng Y, Schorey JS. Extracellular vesicles deliver mycobacterium RNA to promote host immunity and bacterial killing[J]. EMBO Rep, 2019, 20(3): e46613.
[42]	Shariq M, Quadir N, Alam A, et al. The exploitation of host autophagy and ubiquitin machinery by mycobacterium tuberculosis in shaping immune responses and host defense during infection[J]. Autophagy, 2023, 19(1): 3-23.
[43]	Sengupta S, Pattanaik K P, Mishra S, et al. Epigenetic orchestration of host immune defences by mycobacterium tuberculosis[J]. Microbiol Res, 2023, 273: 127400.
[44]	张彩勤, 杨丽, 张廷芬, 等. 结核分枝杆菌分泌蛋白调控巨噬细胞自噬诱导持续性感染[J]. 科学技术与工程, 2018, 18(32): 124-128.
[45]	Ge P, Lei Z, Yu Y, et al. M. tuberculosis PknG manipulates host autophagy flux to promote pathogen intracellular survival[J]. Autophagy, 2022, 18(3): 576-594.
[46]	胡东, 王婉, 赵润鹏, 等. 结核分枝杆菌分泌性酸性磷酸酶(SapM)抑制小鼠巨噬细胞自噬[J]. 细胞与分子免疫学杂志, 2016, 32(6): 726-729.
[47]	Zhang W, Dong C, Xiong S. Mycobacterial SapM hampers host autophagy initiation for intracellular bacillary survival via dephosphorylating raptor[J]. iScience, 2024, 27(5): 109671.
[48]	Duan L, Yi M, Chen J, et al. mycobacterium tuberculosis EIS gene inhibits macrophage autophagy through up-regulation of IL-10 by increasing the acetylation of histone H3[J]. Biochem Biophys Res Commun, 2016, 473(4): 1229-1234.
[49]	Shin DM, Jeon BY, Lee HM, et al. Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling[J]. PLoS Pathog, 2010, 6(12): e1001230.
[50]	Strong EJ, Wang J, Ng TW, et al. Mycobacterium tuberculosis PPE51 inhibits autophagy by suppressing toll-like receptor 2-dependent signaling[J]. mBio, 2022, 13(3): e297421.
[51]	Bah A, Sanicas M, Nigou J, et al. The lipid virulence factors of mycobacterium tuberculosis exert multilayered control over autophagy-related pathways in infected human macrophages[J]. Cells, 2020, 9(3): 666.
[52]	Sengupta S, Nayak B, Meuli M, et al. Mycobacterium tuberculosis phosphoribosyltransferase promotes bacterial survival in macrophages by inducing histone hypermethylation in autophagy-related genes[J]. Front Cell Infect Microbiol, 2021, 11: 676456.
[53]	Dai Y, Zhu C, Xiao W, et al. Mycobacterium tuberculosis hijacks host TRIM21- and NCOA4-dependent ferritinophagy to enhance intracellular growth[J]. J Clin Invest, 2023, 133(8): e159941.
[54]	Chen DY, Chen YM, Lin CF, et al. MicroRNA-889 inhibits autophagy to maintain mycobacterial survival in patients with latent tuberculosis infection by targeting TWEAK[J]. mBio, 2020, 11(1).
[55]	Kim JK, Kim TS, Basu J, et al. MicroRNA in innate immunity and autophagy during mycobacterial infection[J]. Cell Microbiol, 2017, 19(1). Epub 2016 Nov 28.
[56]	Kim JK, Lee HM, Park KS, et al. MIR144* inhibits antimicrobial responses against mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2[J]. Autophagy, 2017, 13(2): 423-441. doi: 10.1080/15548627.2016.1241922 pmid: 27764573
[57]	Koster S, Upadhyay S, Chandra P, et al. Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA[J]. Proc Natl Acad Sci U S A, 2017, 114(41): E8711-E8720.
[58]	Wang C, Hua J, He X, et al. A diagnostic model for distinguishing between active tuberculosis and latent tuberculosis infection based on the blood expression profiles of autophagy-related genes[J]. Ther Adv Respir Dis, 2023, 17: 1611170170.
[59]	Sheng Y, Hua H, Yong Y, et al. Identification of hub genes and typing of tuberculosis infections based on autophagy-related genes[J]. Pol J Microbiol, 2023, 72(3): 223-238. doi: 10.33073/pjm-2023-022 pmid: 37725899
[60]	Li F, Gao B, Xu W, et al. The defect in autophagy induction by clinical isolates of mycobacterium tuberculosis is correlated with poor tuberculosis outcomes[J]. PLoS One, 2016, 11(1): e147810.
[61]	杨国玲, 沙巍. 新型抗结核化学药物的研究进展[J]. 抗感染药学, 2023, 20(10): 1033-1041. doi: 10.13493/j.issn.1672-7878.2023.10-006
[62]	Udinia S, Suar M, Kumar D. Host-directed therapy against tuberculosis: Concept and recent developments[J]. J Biosci, 2023, 48.
[63]	Paik S, Kim JK, Chung C, et al. Autophagy: A new strategy for host-directed therapy of tuberculosis[J]. Virulence, 2019, 10(1): 448-459. doi: 10.1080/21505594.2018.1536598 pmid: 30322337
[64]	Young C, Walzl G, Du Plessis N. Therapeutic host-directed strategies to improve outcome in tuberculosis[J]. Mucosal Immunol, 2020, 13(2): 190-204. doi: 10.1038/s41385-019-0226-5 pmid: 31772320
[65]	Ganmaa D, Uyanga B, Zhou X, et al. Vitamin D supplements for prevention of tuberculosis infection and disease[J]. N Engl J Med, 2020, 383(4): 359-368.
[66]	袁乐永, 柯尊琼. 睾酮对结核分枝杆菌感染的RAW264.7细胞自噬的影响[J]. 免疫学杂志, 2019, 35(9): 785-789.
[67]	Choi SW, Gu Y, Peters RS, et al. Ambroxol induces autophagy and potentiates rifampin antimycobacterial activity[J]. Antimicrob Agents Chemother, 2018, 62(9): e01019-18.
[68]	Juarez E, Carranza C, Sanchez G, et al. Loperamide restricts intracellular growth of mycobacterium tuberculosis in lung macrophages[J]. Am J Respir Cell Mol Biol, 2016, 55(6): 837-847.
[69]	Ouyang Q, Zhang K, Lin D, et al. Bazedoxifene suppresses intracellular mycobacterium tuberculosis growth by enhancing autophagy[J]. mSphere, 2020, 5(2):e00124-20.
[70]	Boland R, Heemskerk MT, Forn-Cuni G, et al. Repurposing tamoxifen as potential host-directed therapeutic for tuberculosis[J]. mBio, 2023, 14(1): e302422.
[71]	Wang J, Sha J, Strong E, et al. FDA-approved amoxapine effectively promotes macrophage control of Mycobacteria by inducing autophagy[J]. Microbiol Spectr, 2022, 10(5): e250922.
[72]	李百远, 李元军, 高非凡. 二甲双胍辅助抗结核的作用机制及临床价值[J]. 临床荟萃, 2021, 36(2): 179-183.
[73]	Parihar SP, Guler R, Khutlang R, et al. Statin therapy reduces the mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autophagy and phagosome maturation[J]. J Infect Dis, 2014, 209(5): 754-763. doi: 10.1093/infdis/jit550 pmid: 24133190
[74]	Dutta NK, Bruiners N, Zimmerman MD, et al. Adjunctive host-directed therapy with statins improves tuberculosis-related outcomes in mice[J]. J Infect Dis, 2020, 221(7): 1079-1087. doi: 10.1093/infdis/jiz517 pmid: 31605489
[75]	Mishra A, Kumar A, Naik L, et al. Soybean lectin-triggered IL-6 secretion induces autophagy to kill intracellular mycobacteria through P2RX7 dependent activation of the JAK2/STAT3/Mcl-1 pathway[J]. Cytokine, 2023, 171: 156366.
[76]	Mishra A, Behura A, Kumar A, et al. Soybean lectin induces autophagy through P2RX7 dependent activation of NF-kappaB-ROS pathway to kill intracellular mycobacteria[J]. Biochim Biophys Acta Gen Subj, 2021, 1865(2): 129806.
[77]	侯良绢, 李晓朋, 赵春娥, 等. 黄芪注射液对肺结核大鼠免疫功能、自噬和凋亡的影响[J]. 中国临床药理学杂志, 2022, 38(10): 1092-1096.
[78]	He W, Sun J, Zhang Q, et al. Andrographolide exerts anti-inflammatory effects in mycobacterium tuberculosis-infected macrophages by regulating the Notch1/Akt/NF-kappaB axis[J]. J Leukoc Biol, 2020, 108(6): 1747-1764.
[79]	Sharma V, Makhdoomi M, Singh L, et al. Trehalose limits opportunistic mycobacterial survival during HIV co-infection by reversing HIV-mediated autophagy block[J]. Autophagy, 2021, 17(2): 476-495.
[80]	Zhang Q, Sun J, Wang Y, et al. Antimycobacterial and anti-inflammatory mechanisms of baicalin via induced autophagy in macrophages infected with mycobacterium tuberculosis[J]. Front Microbiol, 2017, 8: 2142. doi: 10.3389/fmicb.2017.02142 pmid: 29163427
[81]	Zhang S, Zhou X, Ou M, et al. Berbamine promotes macrophage autophagy to clear mycobacterium tuberculosis by regulating the ROS/Ca(2+) axis[J]. mBio, 2023, 14(4): e27223.
[82]	Lee HJ, Ko HJ, Kim SH, et al. Pasakbumin A controls the growth of mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages[J]. PLoS One, 2019, 14(3): e199799.
[83]	Shen J, Fu Y, Liu F, et al. Ursolic acid promotes autophagy by inhibiting Akt/mTOR and TNF-alpha/TNFR1 signaling pathways to alleviate pyroptosis and necroptosis in mycobacterium tuberculosis-infected macrophages[J]. Inflammation, 2023, 46(5): 1749-1763.
[84]	Singh P, Subbian S. Harnessing the mTOR pathway for tuberculosis treatment[J]. Front Microbiol, 2018, 9: 70. doi: 10.3389/fmicb.2018.00070 pmid: 29441052
[85]	Rekha RS, Rao MS, Wan M, et al. Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of mycobacterium tuberculosis in human macrophages[J]. Autophagy, 2015, 11(9): 1688-1699. doi: 10.1080/15548627.2015.1075110 pmid: 26218841
[86]	Smyth R, Berton S, Rajabalee N, et al. Protein kinase r restricts the intracellular survival of mycobacterium tuberculosis by promoting selective autophagy[J]. Front Microbiol, 2020, 11: 613963.
[87]	Hu Y, Wen Z, Liu S, et al. Ibrutinib suppresses intracellular mycobacterium tuberculosis growth by inducing macrophage autophagy[J]. J Infect, 2020, 80(6): e19-e26. doi: 10.1016/j.jinf.2020.03.003 pmid: 32171871
[88]	Fu J, Luo X, Lin M, et al. Marine-fungi-derived gliotoxin promotes autophagy to suppress mycobacteria tuberculosis infection in macrophage[J]. Mar Drugs, 2023, 21(12): 616.
[89]	Mawatwal S, Behura A, Mishra A, et al. Calcimycin induced IL-12 production inhibits intracellular mycobacterial growth by enhancing autophagy[J]. Cytokine, 2018, 111: 1-12. doi: S1043-4666(18)30331-4 pmid: 30081297
[90]	Geng S, Hao P, Wang D, et al. Zinc oxide nanoparticles have biphasic roles on mycobacterium-induced inflammation by activating autophagy and ferroptosis mechanisms in infected macrophages[J]. Microb Pathog, 2023, 180: 106132.
[91]	Gupta PK, Jahagirdar P, Tripathi D, et al. Macrophage targeted polymeric curcumin nanoparticles limit intracellular survival of mycobacterium tuberculosis through induction of autophagy and augment anti-TB activity of isoniazid in RAW 264.7 macrophages[J]. Front Immunol, 2023, 14: 1233630.

分类	名称	作用和可能机制
传统药物	维生素D^[65]	促进自噬,改善免疫调节
	睾酮^[66]	激活JNK信号通路,诱导自噬
	氨溴索^[67]	诱导自噬,促进巨噬细胞中MTB杀伤;增强利福平活性
	洛哌丁胺^[68]	增加LC3与MTB共定位,减少MTB复制
	巴多昔芬^[69]、他莫昔芬^[70]	抑制AKT/mTOR信号传导,促进自噬,抑制MTB生长
	阿莫沙平^[71]	诱导mTOR依赖性自噬,促进MTB杀伤
	二甲双胍^[72]	诱导自噬,减轻炎症;增强抗结核药物疗效
	他汀类药物^[73-74]	增强自噬,促进吞噬体成熟
植物提取物	大豆凝集素^[75-76]	通过NF-κB/ROS和JAK2/STAT3/MCL-1信号通路,促进自噬
	黄芪注射液^[77]	激活PI3K/AKT信号通路,抑制自噬
	穿心莲内酯^[78]	抑制NOTCH1/AKT/NF-κB信号通路,诱导自噬;抑制NLRP3炎症小体和IL-1β
	海藻糖^[79]	激活PI3K,导致TFEB核易位,以MCOLN1依赖性方式诱导自噬
	黄芩素^[80]	抑制PI3K/AKT/NF-κB信号通路,诱导自噬;抑制NLRP3炎症小体和IL-1β
	小檗胺^[81]	调节ROS/Ca²⁺轴激活巨噬细胞自噬
	Pasakbumin A^[82]	通过ERK1/2介导的信号通路诱导自噬,抑制MTB生长
	熊果酸^[83]	抑制AKT/mTOR和TNF-α/TNFR1信号通路,促进自噬
化学合成物及其他	雷帕霉素^[84]	诱导自噬,增加巨噬细胞防御MTB能力
	4-苯基丁酸钠^[85]	依赖于抗菌肽LL-37促进自噬
	蛋白激酶R^[86]	激活自噬,抑制MTB存活
	伊鲁替尼^[87]	抑制BTK/Akt/mTOR通路诱导自噬
	胶霉毒素^[88]	增加LC3-II/LC3-I和ATG5表达,促进自噬。
	卡西霉素^[89]	与P2RX7协同调控JNK-NF-κB信号通路,促进自噬,抑制MTB生长
	氧化锌纳米颗粒^[90]	剂量依赖性方式增强巨噬细胞自噬
	姜黄素纳米颗粒^[91]	诱导自噬,抑制MTB耐药菌株的存活

分类	名称	作用和可能机制
传统药物	维生素D^[65]	促进自噬,改善免疫调节
	睾酮^[66]	激活JNK信号通路,诱导自噬
	氨溴索^[67]	诱导自噬,促进巨噬细胞中MTB杀伤;增强利福平活性
	洛哌丁胺^[68]	增加LC3与MTB共定位,减少MTB复制
	巴多昔芬^[69]、他莫昔芬^[70]	抑制AKT/mTOR信号传导,促进自噬,抑制MTB生长
	阿莫沙平^[71]	诱导mTOR依赖性自噬,促进MTB杀伤
	二甲双胍^[72]	诱导自噬,减轻炎症;增强抗结核药物疗效
	他汀类药物^[73-74]	增强自噬,促进吞噬体成熟
植物提取物	大豆凝集素^[75-76]	通过NF-κB/ROS和JAK2/STAT3/MCL-1信号通路,促进自噬
	黄芪注射液^[77]	激活PI3K/AKT信号通路,抑制自噬
	穿心莲内酯^[78]	抑制NOTCH1/AKT/NF-κB信号通路,诱导自噬;抑制NLRP3炎症小体和IL-1β
	海藻糖^[79]	激活PI3K,导致TFEB核易位,以MCOLN1依赖性方式诱导自噬
	黄芩素^[80]	抑制PI3K/AKT/NF-κB信号通路,诱导自噬;抑制NLRP3炎症小体和IL-1β
	小檗胺^[81]	调节ROS/Ca²⁺轴激活巨噬细胞自噬
	Pasakbumin A^[82]	通过ERK1/2介导的信号通路诱导自噬,抑制MTB生长
	熊果酸^[83]	抑制AKT/mTOR和TNF-α/TNFR1信号通路,促进自噬
化学合成物及其他	雷帕霉素^[84]	诱导自噬,增加巨噬细胞防御MTB能力
	4-苯基丁酸钠^[85]	依赖于抗菌肽LL-37促进自噬
	蛋白激酶R^[86]	激活自噬,抑制MTB存活
	伊鲁替尼^[87]	抑制BTK/Akt/mTOR通路诱导自噬
	胶霉毒素^[88]	增加LC3-II/LC3-I和ATG5表达,促进自噬。
	卡西霉素^[89]	与P2RX7协同调控JNK-NF-κB信号通路,促进自噬,抑制MTB生长
	氧化锌纳米颗粒^[90]	剂量依赖性方式增强巨噬细胞自噬
	姜黄素纳米颗粒^[91]	诱导自噬,抑制MTB耐药菌株的存活

自噬与结核病相关性的研究进展

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 2

参考文献 91

相关文章 15

编辑推荐

Metrics

本文评价

[1]	陈岚, 李叶琼, 冶秀鹏. 费城染色体阴性骨髓增殖性肿瘤患者血栓形成影响因素[J]. 临床荟萃, 2024, 39(4): 370-375.
[2]	尹大鹏, 郭志新. 自噬在糖尿病认知功能障碍中的研究进展[J]. 临床荟萃, 2024, 39(3): 279-283.
[3]	左腾, 王俊祥. 血清阴性类风湿关节炎发病机制的研究进展[J]. 临床荟萃, 2023, 38(8): 753-756.
[4]	陈婷, 刘金彦. 中药靶向PI3K/Akt/mTOR通路调节自噬在糖尿病肾脏病中的研究进展[J]. 临床荟萃, 2023, 38(6): 564-568.
[5]	贾丽娜, 吴美妮, 尹昌浩. 2型糖尿病认知功能障碍发病机制的研究进展[J]. 临床荟萃, 2023, 38(6): 554-558.
[6]	邹琳, 崔轶霞, 张娜娜, 陈思荣. 类风湿关节炎合并骨质疏松症发病机制和相关治疗药物对骨质疏松症影响的研究进展[J]. 临床荟萃, 2023, 38(3): 279-284.
[7]	彭艳, 白碧玥, 朱晓峰, 尹昌浩. 酒精使用障碍患者认知功能损害发病机制的研究进展[J]. 临床荟萃, 2023, 38(12): 1131-1134.
[8]	杨晓蓉, 周淑红, 潘亮, 郭莉江. 结缔组织病相关肺动脉高压的发病机制及其筛查的研究进展[J]. 临床荟萃, 2023, 38(10): 944-948.
[9]	曾晓晴, 庄伟端, 陈丽芬. 卒中后癫痫发作发病机制的研究进展[J]. 临床荟萃, 2022, 37(2): 174-177.
[10]	李朝俊, 孙诚鸿, 金文宇. 非结核分枝杆菌肺病与耐多药肺结核的胸部CT征象对照分析[J]. 临床荟萃, 2021, 36(6): 530-534.
[11]	马光宇1，付冰冰2，孙晓鹏2. 细胞自噬与狼疮肾炎研究进展[J]. 临床荟萃, 2020, 35(7): 662-666.
[12]	张慧卿，路延朋，宋学琴. CAPN3基因突变导致的Calpainopathy的发病机制、临床表现和实验室检测研究进展[J]. 临床荟萃, 2020, 35(6): 564-567.
[13]	李晶雪，李哲，王天俊. 帕金森病伴发抑郁发病机制及治疗的研究进展[J]. 临床荟萃, 2019, 34(8): 759-763.
[14]	李晶雪，王天俊. 卒中后抑郁发病机制及治疗研究进展[J]. 临床荟萃, 2019, 34(6): 572-576.
[15]	冯三丽1, 2，张静楠2，乔淑凯2，王文飞1，李扬2，邢丽娜2，郭晓楠2. 原发性骨髓纤维化伴阵发性睡眠性血红蛋白尿1例并文献复习[J]. 临床荟萃, 2019, 34(12): 1119-1122.