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放射性肺损伤发生机制研究进展
应航洁, 陈亚梅, 陈梦圆, 方敏, 陈明
浙江省肿瘤医院放疗科 中国科学院大学附属医院 中国科学院肿瘤与基础医学研究所,杭州 310022
Research progress on the mechanism of radiation-induced lung injury
Ying Hangjie, Chen Yamei, Chen Mengyuan, Fang Min, Chen Ming
Department of Radiation Oncology, Zhejiang Cancer Hospital, Cancer Hospital of University of Chinese Academy of Sciences, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Hangzhou 310022, China
Abstract：Radiation-induced lung injury (RILI) is a common complication in thoracic cancer patients through radiotherapy, which can be divided into the early-stage radiation-induced pneumonitis (RP) and late-stage radiation-induced lung fibrosis (RILF). At present, glucocorticoids are mainly adopted in the clinical treatment of RP. However, there has been no effective medical treatment for RILF. RILF patients will eventually die from respiratory failure. The exact mechanism of RILI remains unclear. Current studies have proposed that its possible pathogenesis might consist of genetic heterogeneity, oxidative stress and cell damage. In this review, studies related to the pathogenesis of RILI were summarized.
Ying Hangjie,Chen Yamei,Chen Mengyuan et al. Research progress on the mechanism of radiation-induced lung injury[J]. Chinese Journal of Radiation Oncology, 2021, 30(2): 213-216.
[1] Hanania AN, Mainwaring W, Ghebre YT, et al. Radiation-induced lung injury:assessment and management[J]. Chest, 2019, 156(1):150-162. DOI:10. 1016/j. chest. 2019. 03. 033. [2] Rajan Radha R, Chandrasekharan G. Pulmonary injury associated with radiation therapy-assessment, complications and therapeutic targets[J]. Biomed Pharmacother, 2017, 89:1092-1104. DOI:10. 1016/j. biopha. 2017. 02. 106. [3] Yuan X, Liao Z, Liu Z, et al. Single nucleotide polymorphism at rs1982073:T869C of the TGF-beta 1 gene is associated with the risk of radiation pneumonitis in patients with non-small-cell lung cancer treated with definitive radiotherapy[J]. J Clin Oncol, 2009, 27(20):3370-3378. DOI:10. 1200/JCO. 2008. 20. 6763. [4] Yin M, Liao Z, Liu Z, et al. Functional polymorphisms of base excision repair genes XRCC1 and APEX1 predict risk of radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy[J]. Int J Radiat Oncol Biol Phys, 2011, 81(3):67-73. DOI:10. 1016/j. ijrobp. 2010. 11. 079. [5] Mak RH, Alexander BM, Asomaning K, et al. A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy[J]. Cancer, 2012, 118(14):3654-3665. DOI:10. 1002/cncr. 26667. [6] Amirifar P, Ranjouri MR, Yazdani R, et al. Ataxia-telangiectasia:a review of clinical features and molecular pathology[J]. Pediatr Allergy Immunol, 2019, 30(3):277-288. DOI:10. 1111/pai. 13020. [7] Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, et al. Nijmegen breakage syndrome (NBS)[J]. Orphanet J Rare, 2012, 28(7):13. DOI:10. 1186/1750-1172-7-13. [8] Kunwar A, Haston CK. Basal levels of glutathione peroxidase correlate with onset of radiation induced lung disease in inbred mouse strains[J]. Am J Physiol Lung Cell Mol Physiol, 2014, 307(8):597-604. DOI:10. 1152/ajplung. 00088. 2014. [9] Murray LA, Chen Q, Kramer MS, et al. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P[J]. Int J Biochem Cell Biol, 2011,43(1):154-162. DOI:10. 1016/j. biocel. 2010. 10. 013. [10] 张艺凡,何成诗,郞锦义,等. 放射性肺损伤机制及相关因子研究进展[J]. 云南中医中药杂志, 2015, 36(5):81-83. DOI:10. 16254/j. cnki. 53-1120/r. 2015. 05. 042. Zhang YF,He CS, Lang JY, et al. Research progress on the mechanism and related factors of radiation-induced lung injury[J]. Yunnan J Tradit Chin Med Mater Medica, 2015, 36(5):81-83. DOI:10. 16254/j. cnki. 53-1120/r. 2015. 05. 042. [11] Lierova A, Jelicova M, Nemcova M, et al. Cytokines and radiation-induced pulmonary injuries[J]. J Radiat Res, 2018, 59(6):709-753. DOI:10. 1093/jrr/rry067. [12] Xu L, Xiong S, Guo R, et al. Transforming growth factor-β3 attenuates the development of radiation-induced pulmonary fibrosis in mice by decreasing fibrocyte recruitment and regulating IFN-γ/IL-4 balance[J]. Immunol Lett, 2014, 162(1 Pt A):27-33. DOI:10. 1016/j. imlet. 2014. 06. 010. [13] Chiang CS, Liu WC, Jung SM, et al. Compartmental responses after thoracic irradiation of mice:strain differences[J]. Int J Radiat Oncol Biol Phys, 2005, 62(3):862-871. DOI:10.1016/j.ijrobp.2005.02.037. [14] Paun A, Bergeron ME, Haston CK. The Th1/Th17 balance dictates the fibrosis response in murine radiation-induced lung disease[J]. Sci Rep, 2017, 7(1):11586. DOI:10. 1038/s41598-017-11656-5. [15] Büttner C, Skupin A, Reimann T, et al. Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats:macrophages as a prominent source of interleukin-4[J]. Am J Respir Cell Mol Biol, 1997, 17(3):315-325. DOI:10. 1165/ajrcmb. 17. 3. 2279. [16] Zhang C, Zhao H, Li BL, et al. CpG-oligodeoxynucleotides may be effective for preventing ionizing radiation induced pulmonary fibrosis[J]. Toxicol Lett, 2018, 292:181-189. DOI:10. 1016/j. toxlet. 2018. 04. 009. [17] Reiman RM, Thompson RW, Feng CG, et al. Interleukin-5(IL-5) augments the progression of liver fibrosis by regulating IL-13 activity[J]. Infect Immun, 2006, 74(3):1471-1479. DOI:10. 1128/IAI. 74. 3. [18] Park SW, Ahn MH, Jang HK, et al. Interleukin-13 and its receptors in idiopathic interstitial pneumonia:clinical implications for lung function[J]. J Korean Med Sci, 2009, 24(4):614-620. DOI:10. 3346/jkms. 2009. 24. 4. 614. [19] Lee JW, Zoumalan RA, Valenzuela CD, et al. Regulators and mediators of radiation-induced fibrosis:Gene expression profiles and a rationale for Smad3 inhibition[J]. Otolaryngol Head Neck Surg, 2010, 143(4):525-530. DOI:10. 1016/j. otohns. 2010. 06. 912. [20] Chung SI, Horton JA, Ramalingam TR, et al. IL-13 is a therapeutic target in radiation lung injury[J]. Sci Rep, 2016, 22:39714. DOI:10. 1038/srep39714. [21] Paats MS, Bergen IM, Hanselaar WE, et al. T helper 17 cells are involved in the local and systemic inflammatory response in community-acquired pneumonia[J]. Thorax, 2013, 68(5):468-474. DOI:10. 1136/thoraxjnl-2012-202168. [22] Cappuccini F, Eldh T, Bruder D, et al. New insights into the molecular pathology of radiation-induced pneumopathy[J]. Radiother Oncol, 2011, 101(1):86-92. DOI:10. 1016/j. radonc. [23] Wang Y, Xu G, Wang J, et al. Relationship of Th17/Treg cells and radiation pneumonia in locally advanced esophageal carcinoma.[J]. Anticancer Res, 2017, 37(8):4643-4647. DOI:10. 21873/anticanres. 11866. [24] Xiong S, Guo R, Yang Z, et al. Treg depletion attenuates irradiation-induced pulmonary fibrosis by reducing fibrocyte accumulation, inducing Th17 response, and shifting IFN-γ, IL-12/IL-4, IL-5 balance[J]. Immunobiology, 2015, 220(11):1284-1291. DOI:10. 1016/j. imbio. 2015. 07. 001. [25] S N SG, Raviraj R, Nagarajan D, et al. Radiation-induced lung injury:impact on macrophage dysregulation and lipid alteration-a review[J]. Immunopharmacol Immunotoxicol, 2019, 41(3):370-379. DOI:10. 1080/08923973. 2018. 1533025. [26] Cai Y, Sugimoto C, Arainga M, et al. in vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques:implications for understanding lung disease in humans[J]. J Immunol, 2014, 192(6):2821-2829. DOI:10. 4049/jimmunol. 1302269. [27] Groves AM, Johnston CJ, Misra RS, et al. Whole-lung irradiation results in pulmonary macrophage alterations that are subpopulation and strain specific[J]. Radiat Res, 2015, 184(6):639-649. DOI:10. 1667/RR14178. 1. [28] Meziani L, Mondini M, Petit B, et al. CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages[J]. Eur Respir J, 2018, 51(3):1702120. DOI:10. 1183/13993003. [29] Kong FM, Ao X, Wang L, et al. The use of blood biomarkers to predict radiation lung toxicity:a potential strategy to individualize thoracic radiation therapy[J]. Cancer Control, 2008, 15(2):140-150. DOI:10. 1177/107327480801500206. [30] Sekine I, Sumi M, Ito Y, et al. Retrospective analysis of steroid therapy for radiation-induced lung injury in lung cancer patients[J]. Radiother Oncol, 2006, 80(1):93-97. DOI:10. 1016/j. radonc. 2006. 06. 007. [31] Mathew B, Huang Y, Jacobson JR, et al. Simvastatin attenuates radiation-induced murine lung injury and dysregulated lung gene expression[J]. Am J Respir Cell Mol Biol, 2011, 44(3):415-422. DOI:10. 1165/rcmb. 2010-01220C. [32] Anscher MS, Thrasher B, Zgonjanin L, et al. Small molecular inhibitor of transforming growth factor-beta protects against development of radiation-induced lung injury[J]. Int J Radiat Oncol Biol Phys, 2008, 71(3):829-837. DOI:10.1016/j.ijrobp.2008.02.046. [33] Flechsig P, Dadrich M, Bickelhaupt S, et al. LY2109761 attenuates radiation-induced pulmonary murine fibrosis via reversal of TGF-β and BMP-associated proinflammatory and proangiogenic signals[J]. Clin Cancer Res, 2012, 18(13):3616-3627. DOI:10. 1158/ 1078-0432. CCR-11-2855. [34] Zhao Y, Wang L, Huang Q, et al. Radiosensitization of non-small cell lung cancer cells by inhibition of TGF-β1 signaling with SB431542 is dependent on p53 status[J]. Oncol Res, 2016, 24(1):1-7. DOI:10. 3727/096504016X14570992647087. [35] Choi NC. Radioprotective effect of amifostine in radiation pneumonitis[J]. Semin Oncol, 2003, 30(6 suppl 18):10-17. DOI:10. 1053/j. seminoncol. 2003. 11. 038.
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