脓毒症致急性肺损伤相关的microRNAs研究进展

doi:10.3760/cma.j.issn.1007-1245.2023.04.004

摘要/Abstract

摘要：

脓毒症是导致全球范围内急重症患者死亡的最常见病因，其本质是由于机体促炎和抗炎过程失衡，导致全身炎症级联反应发生和特异性免疫功能障碍，并最终演变成多器官功能障碍综合征（multiple organ dysfunction syndrome，MODS）。在脓毒症的发生发展过程中，肺脏损伤的相关表现尤为常见，继发于脓毒症的急性肺损伤（acute lung injury，ALI）或急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）是脓毒症患者致死的最主要原因。因此，早期识别和诊断脓毒症相关肺损伤对患者诊治具有重要意义。作为一种单链非编码RNAs，microRNAs具有较高的生物特异性、选择性和保守性，当前已作为理想的生物标志物被用于多种疾病的临床诊断。多项研究证实，microRNAs在脓毒症相关肺损伤的发病过程中差异表达，通过监测和分析其变异水平能有效对脓毒症相关肺损伤的诊断及预后进行判断。本文回顾分析microRNAs在脓毒症相关肺损伤中的系列研究，现对异常表达的microRNAs及其在脓毒症相关肺损伤中的作用机制进行综述。

关键词:

脓毒症, 肺损伤, 微RNA, 诊疗价值

Abstract:

Sepsis is the most common cause of death in acute critical patients worldwide. The essence of sepsis is the imbalance of proinflammatory and anti-inflammatory processes in the body, which leads to systemic inflammatory cascade reaction and specific immune dysfunction, and eventually evolves into multi-organ dysfunction syndrome. In the development of sepsis, acute lung injury is particularly common. Acute lung injury or acute respiratory distress syndrome secondary to sepsis are the main causes of death in sepsis patients. Therefore, early identification and diagnosis of sepsis-associated lung injury is of great significance for sepsis patients. As single-chain non-coding RNAs, microRNAs have high biological specificity, selectivity, and conserved properties. Currently, microRNAs have been used as ideal biomarkers for clinical diagnosis of a variety of diseases. Multiple studies have confirmed that microRNAs are differentially expressed in the pathogenesis of sepsis associated with lung injury; monitoring and analyzing their variation levels is effective in the diagnosis and prognosis evaluaiton of sepsis associated with lung injury. In this paper, we review the abnormal expression of microRNAs and their mechanism of action in sepsis associated with lung injury by summarizing a series of studies on microRNAs in sepsis associated with lung injury.

Key words:

Sepsis, Acute lung injury, MicroRNAs, Diagnosis and therapeutic values

王宁宁林家凯罗小燕孙斌.

脓毒症致急性肺损伤相关的microRNAs研究进展 [J]. 国际医药卫生导报, 2023, 29(4): 456-460.

Wang Ningning, Lin Jiakai, Luo Xiaoyan, Sun Bin.

Associated microRNAs in patients with acute lung injury caused by sepsis [J]. International Medicine and Health Guidance News, 2023, 29(4): 456-460.

参考文献

[1] Sun GD, Zhang Y, Mo SS, et al. Multiple organ dysfunction syndrome caused by sepsis: risk factor analysis[J]. Int J Gen Med, 2021,14:7159-7164. DOI: 10.2147/IJGM.S328419.
[2] Ziesmann MT, Marshall JC. Multiple organ dysfunction: the defining syndrome of sepsis[J]. Surg Infect (Larchmt), 2018,19(2):184-190. DOI: 10.1089/sur.2017.298.
[3] Lonsdale DO, Shah RV, Lipman J. Infection, sepsis and the inflammatory response: mechanisms and therapy[J]. Front Med (Lausanne), 2020,7:588863. DOI: 10.3389/fmed.2020.588863.
[4] Huang X, Xiu H, Zhang S, et al. The role of macrophages in the pathogenesis of ALI/ARDS[J]. Mediators Inflamm, 2018,2018:1264913. DOI: 10.1155/2018/1264913.
[5] Zhou J, Peng Z, Wang J. Trelagliptin alleviates lipopolysaccharide (LPS)-induced inflammation and oxidative stress in acute lung injury mice[J]. Inflammation, 2021,44(4):1507-1517. DOI: 10.1007/s10753-021-01435-w.
[6] Wang X, Yang B, Li Y, et al. AKR1C1 alleviates LPS-induced ALI in mice by activating the JAK2/STAT3 signaling pathway[J]. Mol Med Rep, 2021,24(6):833. DOI: 10.3892/mmr.2021.12473.
[7] Van Looveren K, Van Wyngene L, Libert C. An extracellular microRNA can rescue lives in sepsis[J]. EMBO Rep, 2020,21(1):e49193. DOI: 10.15252/embr.201949193.
[8] Yuan FH, Chen YL, Zhao Y, et al. microRNA-30a inhibits the liver cell proliferation and promotes cell apoptosis through the JAK/STAT signaling pathway by targeting SOCS-1 in rats with sepsis[J]. J Cell Physiol, 2019,234(10):17839-17853. DOI: 10.1002/jcp.28410.
[9] Zhang Y, Huang H, Liu W, et al. Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression[J]. Cell Death Dis, 2021,12(4):335. DOI: 10.1038/s41419-021-03578-y.
[10] Ojha R, Nandani R, Pandey RK, et al. Emerging role of circulating microRNA in the diagnosis of human infectious diseases[J]. J Cell Physiol, 2019,234(2):1030-1043. DOI: 10.1002/jcp.27127.
[11] Zhang Y, Huang T, Jiang L, et al. MCP-induced protein 1 attenuates sepsis-induced acute lung injury by modulating macrophage polarization via the JNK/c-Myc pathway[J]. Int Immunopharmacol, 2019,75:105741. DOI: 10.1016/j.intimp.2019.105741.
[12] Garg AD, Galluzzi L, Apetoh L, et al. Molecular and translational classifications of DAMPs in immunogenic cell death[J]. Front Immunol, 2015,6:588. DOI: 10.3389/fimmu.2015.00588.
[13] Zhang ZM, Wang YC, Chen L, et al. Protective effects of the suppressed NF-κB/TLR4 signaling pathway on oxidative stress of lung tissue in rat with acute lung injury[J]. Kaohsiung J Med Sci, 2019,35(5):265-276. DOI: 10.1002/kjm2.12065.
[14] Zhu WD, Xu J, Zhang M, et al. MicroRNA-21 inhibits lipopolysaccharide-induced acute lung injury by targeting nuclear factor-κB[J]. Exp Ther Med, 2018,16(6):4616-4622. DOI: 10.3892/etm.2018.6789.
[15] Fu S. MicroRNA-17 contributes to the suppression of the inflammatory response in lipopolysaccharide-induced acute lung injury in mice via targeting the toll-like receptor 4/nuclear factor-κB pathway[J]. Int J Mol Med, 2020,46(1):131-140. DOI: 10.3892/ijmm.2020.4599.
[16] Monahan LJ. Acute respiratory distress syndrome[J]. Curr Probl Pediatr Adolesc Health Care, 2013,43(10):278-84. DOI: 10.1016/j.cppeds.2013.10.004.
[17] Jiao Y, Zhang T, Zhang C, et al. Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury[J]. Crit Care, 2021,25(1):356. DOI: 10.1186/s13054-021-03775-3.
[18] Tian J, Cui X, Sun J, et al. Exosomal microRNA-16-5p from adipose mesenchymal stem cells promotes TLR4-mediated M2 macrophage polarization in septic lung injury[J]. Int Immunopharmacol, 2021,98:107835. DOI: 10.1016/j.intimp.2021.107835.
[19] Hu X, Li J, Fu M, et al. The JAK/STAT signaling pathway: from bench to clinic[J]. Signal Transduct Target Ther, 2021,6(1):402. DOI: 10.1038/s41392-021-00791-1.
[20] O'SheaJJ, SchwartzDM, VillarinoAV, et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention[J]. Annu Rev Med, 2015,66:311-328. DOI: 10.1146/annurev-med-051113-024537.
[21] LiauNPD, LaktyushinA, LucetIS, et al. The molecular basis of JAK/STAT inhibition by SOCS1[J]. Nat Commun, 2018,9(1):1558. DOI: 10.1038/s41467-018-04013-1.
[22] 李芮,崔云,张育才,等.miR-155抑制剂对内毒素血症小鼠肺组织JAK/STAT1信号通路的影响[J].中华急诊医学杂志,2015,24(8):839-844.DOI:10.3760/cma.j.issn.1671-0282.2015.08.007.
[23] Yan J, Yang F, Wang D, et al. MicroRNA-217 modulates inflammation, oxidative stress, and lung injury in septic mice via SIRT1[J]. Free Radic Res, 2021,55(1):1-10. DOI: 10.1080/10715762.2020.1852234.
[24] Song H, Chen Q, Xie S, et al. GDF-15 prevents lipopolysaccharide-mediated acute lung injury via upregulating SIRT1[J]. Biochem Biophys Res Commun, 2020,526(2):439-446. DOI: 10.1016/j.bbrc.2020.03.103.
[25] Liu X, Jin X, Yu D, et al. Suppression of NLRP3 and NF-κB signaling pathways by α-Cyperone via activating SIRT1 contributes to attenuation of LPS-induced acute lung injury in mice[J]. Int Immunopharmacol,2019 ,76:105886. DOI: 10.1016/j.intimp.2019.105886.
[26] Chen L, Xie W, Wang L, et al. MiRNA-133a aggravates inflammatory responses in sepsis by targeting SIRT1[J]. Int Immunopharmacol, 2020,88:106848. DOI: 10.1016/j.intimp.2020.106848.
[27] Lee J, Song CH. Effect of reactive oxygen species on the endoplasmic reticulum and mitochondria during intracellular pathogen infection of mammalian cells[J]. Antioxidants (Basel), 2021,10(6):872. DOI: 10.3390/antiox10060872.
[28] Zhang Q, Kuang H, Chen C, et al. The kinase Jnk2 promotes stress-induced mitophagy by targeting the small mitochondrial form of the tumor suppressor ARF for degradation[J]. Nat Immunol, 2015,16(5):458-466. DOI: 10.1038/ni.3130.
[29] Yang J, Do-Umehara HC, Zhang Q, et al. miR-221-5p-mediated downregulation of JNK2 aggravates acute lung injury[J]. Front Immunol, 2021,12:700933. DOI: 10.3389/fimmu.2021.700933.
[30] Bedoui S, Herold MJ, Strasser A. Emerging connectivity of programmed cell death pathways and its physiological implications[J]. Nat Rev Mol Cell Biol, 2020,21(11):678-695. DOI: 10.1038/s41580-020-0270-8.
[31] Liu Y, Chen C, Sun Q, et al. Mesenteric lymph duct drainage attenuates lung inflammatory injury and inhibits endothelial cell apoptosis in septic rats[J]. Biomed Res Int, 2020,2020:3049302. DOI: 10.1155/2020/3049302.
[32] Yi L, Chang M, Zhao Q, et al. Genistein-3'-sodium sulphonate protects against lipopolysaccharide-induced lung vascular endothelial cell apoptosis and acute lung injury via BCL-2 signalling[J]. J Cell Mol Med, 2020,24(1):1022-1035. DOI: 10.1111/jcmm.14815.
[33] Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins[J]. Nat Rev Mol Cell Biol, 2019,20(3):175-193. DOI: 10.1038/s41580-018-0089-8.
[34] Siddiqi S, Sussman MA. Cell and gene therapy for severe heart failure patients: the time and place for Pim-1 kinase[J]. Expert Rev Cardiovasc Ther, 2013,11(8):949-957. DOI: 10.1586/14779072.2013.814830.
[35] Zheng D, Yu Y, Li M, et al. Inhibition of microRNA 195 prevents apoptosis and multiple-organ injury in mouse models of sepsis[J]. J Infect Dis, 2016,213(10):1661-1670. DOI: 10.1093/infdis/jiv760.
[36] Wang Y, Wang X, Liu W, et al. Role of the Rho/ROCK signaling pathway in the protective effects of fasudil against acute lung injury in septic rats[J]. Mol Med Rep, 2018,18(5):4486-4498. DOI: 10.3892/mmr.2018.9446.
[37] Zhao X, Wang M, Sun Z, et al. MicroRNA-139-5p improves sepsis-induced lung injury by targeting Rho-kinase1[J]. Exp Ther Med, 2021,22(4):1059. DOI: 10.3892/etm.2021.10493.
[38] Kawasaki M, Kuwano K, Hagimoto N, et al. Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor[J]. Am J Pathol, 2000,157(2):597-603. DOI: 10.1016/S0002-9440(10)64570-1.
[39] Liu S, Gao S, Yang Z, et al. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12[J]. Open Med (Wars), 2021,16(1):1109-1120. DOI: 10.1515/med-2021-0258.
[40] Ho J, Yu J, Wong SH, et al. Autophagy in sepsis: degradation into exhaustion?[J].Autophagy,2016,12(7):1073-1082.DOI:10.1080/15548627.2016.1179410.
[41] Mandelbaum J, Rollins N, Shah P, et al. Identification of a lung cancer cell line deficient in atg7-dependent autophagy[J]. Autophagy, version posted online: 19 Jun 2015. DOI: 10.1080/15548627.2015.1056966.
[42] Li G, Wang B, Ding X, et al. Plasma extracellular vesicle delivery of miR-210-3p by targeting ATG7 to promote sepsis-induced acute lung injury by regulating autophagy and activating inflammation[J]. Exp Mol Med, 2021,53(7):1180-1191. DOI: 10.1038/s12276-021-00651-6.
[43] Li LL, Dai B, Sun YH, et al. The activation of IL-17 signaling pathway promotes pyroptosis in pneumonia-induced sepsis[J]. Ann Transl Med, 2020,8(11):674. DOI: 10.21037/atm-19-1739.
[44] Chen S, Ding R, Hu Z, et al. MicroRNA-34a inhibition alleviates lung injury in cecal ligation and puncture induced septic mice[J]. Front Immunol, 2020,11:1829. DOI: 10.3389/fimmu.2020.01829.