BMSC促进巨噬细胞M2型极化减轻急性放射性肺损伤
BMSCs promote M2 macrophage polarization to attenuate acute radiation-induced lung injury
张鑫辉 1牛世英 2姚树桐 1张晓月 3曹雪涛 1高雪 1赵国丽 4陈敬坤 5张月英1
作者信息
- 1. 山东第一医科大学附属第一医院病理科,山东济南 250013;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
- 2. 山东第一医科大学附属第一医院病理科,山东济南 250013;山西省临汾市中心医院病理科,山西临汾 041099
- 3. 山东第一医科大学附属第一医院病理科,山东济南 250013
- 4. 聊城市传染病医院病理科,山东聊城 252002
- 5. 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
- 折叠
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 × l06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Ml型向M2型极化有关.
Abstract
Objective To investigate the therapeutic effects of bone marrow mesenchymal stem cells(BMSCs)for radi-ation-induced lung injury(RILI)and the underlying mechanism.Methods Forty-five healthy adult male C57BL/6 mice were randomly divided into control,model,and BMSCs groups.The model and BMSCs groups received a single irradiation dose of 20 Gy to the chest,while the control group did not receive X-ray irradiation.For the BMSCs group,an injection of 1 × i06 BMSCs cells was administered via the tail vein within 6 h after irradiation.In the 5th week,the lung tissue was taken to observe pathological changes with HE staining;examine the expression of the inflammatory factors interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)with immunohistochemical staining;observe the polarization of macrophages with im-munofluorescence staining;and measure the expression of the epithelial-mesenchymal transition markers E-cadherin,N-cad-herin,and vimentin proteins by Western blot.Results After radiation,the model group developed pulmonary vasodilation and congestion with septal thickening and inflammatory cell infiltration,and these changes were markedly reduced in the BMSCs group.The model group showed significantly down-regulated expression of IL-6 and TNF-α compared with signi-ficantly increased levels in the model group(P＜0.01,P＜0.05).Treatment with BMSCs significantly increased the polariz-ation of lung macrophages towards the M2 type,while significantly decreasing the abnormally increased N-cadherin and vi-mentin levels in RILI mice(P＜0.05,P＜0.01).Conclusion BMSCs have therapeutic effects for RILI mice,which may be through promoting macrophage polarization from Ml to M2.
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Key words
Radiation-induced lung injury/Bone marrow mesenchymal stem cell/Macrophage/Epithelial-mesenchymal transition引用本文复制引用
基金项目
山东省自然科学基金(ZR2020QH208)
山东省医药卫生科技发展计划(202101041037)
山东第一医科大学大学生创新创业训练计划(2022104391726)
出版年
2024
NETL
NSTL
万方数据