BMSC促进巨噬细胞M2型极化减轻急性放射性肺损伤
张鑫辉1,2 , 牛世英1,3 , 姚树桐1,2 , 张晓月1 , 曹雪涛1,2 , 高雪1,2 , 赵国丽4 , 陈敬坤2 , 张月英1,2
1. 山东第一医科大学附属第一医院病理科, 山东 济南 250013; 2. 山东第一医科大学临床与基础医学院病理生理学系, 山东 济南 250117; 3. 山西省临汾市中心医院病理科, 山西 临汾 041099; 4. 聊城市传染病医院病理科, 山东 聊城 252002
BMSCs promote M2 macrophage polarization to attenuate acute radiation-induced lung injury
ZHANG Xinhui1,2 , NIU Shiying1,3 , YAO Shutong1,2 , ZHANG Xiaoyue1 , CAO Xuetao1,2 , GAO Xue1,2 , ZHAO Guoli4 , CHEN Jingkun2 , ZHANG Yueying1,2
1. Department of Pathology, the First Affiliated Hospital of Shandong First Medical University, Jinan 250013 China; 2. Department of Pathophysiology, School of Clinical and Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117 China; 3. Department of Pathology, Linfen Central Hospital, Linfen 041099 China; 4. Department of Pathology, Liaocheng Infectious Disease Hospital, Liaocheng 252002 China
摘要 目的 探讨骨髓间充质干细胞(BMSCs)对放射性肺损伤(RILI)的治疗作用,初步探讨其作用机制。方法 将45只健康成年雄性C57BL/6小鼠随机分为Control组、Model组、BMSCs组。Model组和BMSCs组单次胸部照射剂量为20 Gy,正常对照组不接受X线照射,照射后6 h内,BMSCs组以1×106 个BMSCs通过尾静脉注射小鼠体内。第5周取肺组织HE染色观察肺组织病理变化;免疫组织化学染色观察肺组织炎症因子白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的表达变化;巨噬细胞免疫荧光染色观察肺部巨噬细胞极化的变化;免疫蛋白印迹检测肺组织上皮间质转化标志物上皮钙黏着蛋白(E-cadherin)、神经钙黏着蛋白(N-cadherin)、波形蛋白(Vimentin)的表达。结果 辐射后,Model组肺组织血管扩张充血,肺间隔明显增厚,炎细胞浸润,BMSCs组小鼠肺组织的上述病变明显减轻;Model组明显增高的在炎症因子IL-6和TNF-α的表达在BMSCs组均明显下调(P < 0.01,P < 0.05);BMSCs的治疗显著增加肺部巨噬细胞向M2型极化,同时降低了RILI小鼠体内异常增高的N-cadherin和Vimentin的蛋白水平(P < 0.05, P < 0.01)。结论 BMSCs对小鼠RILI有明显的治疗作用,其机制可能与BMSCs促进巨噬细胞M1型向M2型极化有关。
关键词 :
放射性肺损伤 ,
骨髓间充质干细胞 ,
巨噬细胞极化 ,
上皮间质转化
收稿日期: 2023-09-12
基金资助: 山东省自然科学基金(NoZR2020QH208);山东省医药卫生科技发展计划项目(No202101041037);山东第一医科大学大学生创新创业训练计划项目(2022104391726)
通讯作者:
张月英,E-mail:zhangyueying828@126.com
E-mail: zhangyueying828@126.com
作者简介 : 张鑫辉(1998-),男,山东潍坊人,硕士,从事实验病理学的基础研究工作。E-mail:zxh98117@163.com
引用本文:
张鑫辉, 牛世英, 姚树桐, 张晓月, 曹雪涛, 高雪, 赵国丽, 陈敬坤, 张月英. BMSC促进巨噬细胞M2型极化减轻急性放射性肺损伤[J]. 中国辐射卫生, 2024, 33(1): 21-27.
ZHANG Xinhui, NIU Shiying, YAO Shutong, ZHANG Xiaoyue, CAO Xuetao, GAO Xue, ZHAO Guoli, CHEN Jingkun, ZHANG Yueying. BMSCs promote M2 macrophage polarization to attenuate acute radiation-induced lung injury. Chinese Journal of Radiological Health, 2024, 33(1): 21-27.
链接本文:
http://www.zgfsws.com/CN/10.13491/j.issn.1004-714X.2024.01.004 或 http://www.zgfsws.com/CN/Y2024/V33/I1/21
[1] Bledsoe TJ, Nath SK, Decker RH. Radiation pneumonitis[J]. Clin Chest Med, 2017, 38(2): 201-208. DOI: 10.1016/j.ccm.2016.12.004 [2] 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 [3] Devine A, Marignol L. Potential of amifostine for chemoradiotherapy and radiotherapy-associated toxicity reduction in advanced NSCLC: a meta-analysis[J]. Anticancer Res, 2016, 36(1): 5-12 [4] Niu SY, Zhang YY. Applications and therapeutic mechanisms of action of mesenchymal stem cells in radiation-induced lung injury[J]. Stem Cell Res Ther, 2021, 12(1): 212. DOI: 10.1186/s13287-021-02279-9 [5] Novak ML, Koh TJ. Macrophage phenotypes during tissue repair[J]. J Leukoc Biol, 2013, 93(6): 875-881. DOI: 10.1189/jlb.1012512 [6] 牛世英, 丛昌盛, 孙美丽, 等. 冷诱导RNA结合蛋白在放射性肺损伤模型中的表达变化[J]. 中国辐射卫生,2022,31(1):33-38,46. DOI: 10.13491/j.issn.1004-714X.2022.01.007 Niu SY, Cong CS, Sun ML, et al. Expression of cold-inducible RNA-binding protein in radiation-induced lung injury model[J]. Chin J Radiol Health, 2022, 31(1): 33-38,46. DOI: 10.13491/j.issn.1004-714X.2022.01.007 [7] Van Dyk J, Keane TJ, Kan S, et al. Radiation pneumonitis following large single dose irradiation: a re-evaluation based on absolute dose to lung[J]. Int J Radiat Oncol Biol Phys, 1981, 7(4): 461-467. DOI: 10.1016/0360-3016(81)90131-0 [8] Jiang XP, Jiang X, Qu C, et al. Intravenous delivery of adipose-derived mesenchymal stromal cells attenuates acute radiation-induced lung injury in rats[J]. Cytotherapy, 2015, 17(5): 560-570. DOI: 10.1016/j.jcyt.2015.02.011 [9] Tsoutsou PG, Koukourakis MI. Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research[J]. Int J Radiat Oncol Biol Phys, 2006, 66(5): 1281-1293. DOI: 10.1016/j.ijrobp.2006.08.058 [10] 陈家祯, 王玉, 王存良, 等. 放射性肺损伤发病机制及分子靶向治疗研究进展[J]. 中国辐射卫生,2021,30(3):377-380,390. DOI: 10.13491/j.issn.1004-714X.2021.03.023 Chen JZ, Wang Y, Wang CL, et al. Research progress on pathogenesis and molecular targeted therapy of radiation-induced lung injury[J]. Chin J Radiol Health, 2021, 30(3): 377-380,390. DOI: 10.13491/j.issn.1004-714X.2021.03.023 [11] Zhang Y, Jiang XP, Ren LQ. Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats[J]. Sci Rep, 2019, 9(1): 5589. DOI: 10.1038/s41598-019-41576-5 [12] Chen HX, Xiang H, Xu WH, et al. Manganese superoxide dismutase gene-modified mesenchymal stem cells attenuate acute radiation-induced lung injury[J]. Hum Gene Ther, 2017, 28(6): 523-532. DOI: 10.1089/hum.2016.106 [13] Yahyapour R, Shabeeb D, Cheki M, et al. Radiation protection and mitigation by natural antioxidants and flavonoids: implications to radiotherapy and radiation disasters[J]. Curr Mol Pharmacol, 2018, 11(4): 285-304. DOI: 10.2174/1874467211666180619125653 [14] Giuranno L, Ient J, De Ruysscher D, et al. Radiation-induced lung injury (RILI)[J]. Front Oncol, 2019, 9: 877. DOI: 10.3389/fonc.2019.00877 [15] Parekh KR, Nawroth J, Pai A, et al. Stem cells and lung regeneration[J]. Am J Physiol Cell Physiol, 2020, 319(4): C675-C693. DOI: 10.1152/ajpcell.00036.2020 [16] Ying HJ, Fang M, Hang QQ, et al. Pirfenidone modulates macrophage polarization and ameliorates radiation-induced lung fibrosis by inhibiting the TGF-β1/Smad3 pathway[J]. J Cell Mol Med, 2021, 25(18): 8662-8675. DOI: 10.1111/jcmm.16821 [17] Gao J, Peng S, Shan XN, et al. Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis[J]. Cell Death Dis, 2019, 10(12): 957. DOI: 10.1038/s41419-019-2195-8 [18] Zheng JC, Wang Y, Wang ZW, et al. Near-infrared Nrf2 activator IR-61 dye alleviates radiation-induced lung injury[J]. Free Radic Res, 2022, 56(5/6): 411-426. DOI: 10.1080/10715762.2022.2132942 [19] Zheng L, Zhu Q, Xu C, et al. Glycyrrhizin mitigates radiation-induced acute lung injury by inhibiting the HMGB1/TLR4 signalling pathway[J]. J Cell Mol Med, 2020, 24(1): 214-226. DOI: 10.1111/jcmm.14703 [20] Wu X, Ji H, Wang Y, et al. Melatonin alleviates radiation-induced lung injury via regulation of miR-30e/NLRP3 axis[J]. Oxid Med Cell Longev, 2019, 2019: 4087298. DOI: 10.1155/2019/4087298 [21] Mills CD. M1 and M2 macrophages: oracles of health and disease[J]. Crit Rev Immunol, 2012, 32(6): 463-488. DOI: 10.1615/critrevimmunol.v32.i6.10 [22] Cho DI, Kim MR, Jeong HY, et al. Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages[J]. Exp Mol Med, 2014, 46(1): e70. DOI: 10.1038/emm.2013.135 [23] Abumaree MH, Al Jumah MA, Kalionis B, et al. Human placental mesenchymal stem cells (pMSCs) play a role as immune suppressive cells by shifting macrophage differentiation from inflammatory M1 to anti-inflammatory M2 macrophages[J]. Stem Cell Rev Rep, 2013, 9(5): 620-641. DOI: 10.1007/s12015-013-9455-2 [24] Li MY, Xu JY, Mei XL, et al. Regulatory effects of dermal papillary pluripotent stem cells on polarization of macrophages from M1 to M2 phenotype in vitro[J]. Transpl Immunol, 2019, 52: 57-67. DOI: 10.1016/j.trim.2018.11.003
[1]
高雪, 牛世英, 宋国华, 李露露, 张晓月, 潘文韬, 曹雪涛, 张鑫辉, 孙美丽, 赵国丽, 张月英. 氢气疗法通过抑制NF-κB通路促进巨噬细胞向M2亚型极化 [J]. 中国辐射卫生, 2024, 33(1): 33-39.
[2]
衣峻萱, 董晓丹, 薛文翔, 高姝颖, 薛乃雯, 金顺子. 辐射诱导肺上皮细胞GATA3表达及其RNA甲基化修饰机制 [J]. 中国辐射卫生, 2023, 32(3): 223-229.
[3]
耿爽, 李倩, 郗停停, 王美玉, 郭浩鑫, 王志鑫, 毕晓光, 鄢成名, 杨陟华, 王易龙, 朱茂祥. 补体在放射性肺损伤中的作用与机制 [J]. 中国辐射卫生, 2022, 31(5): 535-541.
[4]
牛世英, 丛昌盛, 孙美丽, 姜一帆, 杨彤, 王兆朋, 张月英. 冷诱导RNA结合蛋白在放射性肺损伤模型中的表达变化 [J]. 中国辐射卫生, 2022, 31(1): 33-38,46.
[5]
陈家祯, 王玉, 王存良, 胡旭东. 放射性肺损伤发病机制及分子靶向治疗研究进展 [J]. 中国辐射卫生, 2021, 30(3): 377-380,390.
[6]
耿继武, 刘浩, 曹立基, 路顺, 韩冬, 陈明, 陈龙华, 周成. 无创吸入式麻醉精准肺野照射装置在小鼠肺损伤研究中的应用 [J]. 中国辐射卫生, 2018, 27(2): 109-113.
[7]
刘主龙, 何方方, 程玉峰. 乳腺托架的应用对肺受照射体积影响的研究 [J]. 中国辐射卫生, 2017, 26(5): 616-618.
[8]
于娟, 苏爽. 呼吸控制对肺癌放射治疗肺损伤相关指标的影响 [J]. 中国辐射卫生, 2010, 19(1): 95-96.