| 孙慧勤,王涛,庞学利,王钰,王锋超,何君,周青,龙爽,冉新泽,粟永萍.粒细胞集落刺激因子动员自体干细胞对放射性肺损伤的防治作用[J].中华放射医学与防护杂志,2019,39(3):178-184 |
| 粒细胞集落刺激因子动员自体干细胞对放射性肺损伤的防治作用 |
| The therapeutic effect of G-CSF-mobilized autologous stem cells on radiation pulmonary injury in mice |
| 投稿时间：2018-06-28 |
| DOI：10.3760/cma.j.issn.0254-5098.2019.03.004 |
| 中文关键词: 放射性肺损伤 粒细胞集落刺激因子 自体干细胞动员 防治 小鼠 |
| 英文关键词:Radiation-induced lung injury G-CSF Autologous stem cell mobilization Therapeutic effect Mice |
| 基金项目:军队后勤科研重大项目（AWS13J002，AWS14J002） |
| 作者 | 单位 | E-mail | | 孙慧勤 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | | | 王涛 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | | | 庞学利 | 西南医院肿瘤放疗科, 重庆 400038 | | | 王钰 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | | | 王锋超 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | | | 何君 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | | | 周青 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | | | 龙爽 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | | | 冉新泽 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | | | 粟永萍 | 陆军军医大学军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室, 防原医学教研室, 重庆 400038 | suyp2003@163.com |
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| 中文摘要: |
| 目的 研究粒细胞集落刺激因子（G-CSF）动员自体干细胞对放射性肺损伤的防治作用。方法 75只C57 BL/6实验小鼠采用随机数表法分为健康对照组、单纯照射组及治疗组。采用胸部单次照射剂量14 Gy建立放射性肺损伤模型，治疗组照前以重组人粒细胞集落刺激因子（G-CSF，250 μg·kg-1·d-1，连续5 d）行自体骨髓干细胞动员，照射后逐日动态观测小鼠一般状况、死亡率，主要于3、4个月时相点通过组织学结合图像分析等方法，比较研究肺损伤及防治效应。结果 胸部局部照射14 Gy是造成小鼠放射性肺纤维化的适宜剂量。单纯照射组小鼠死亡率为37.5%，死亡时间主要在照后11周。治疗组及健康对照组全程无动物死亡。照射后3个月肺系数（肺/体重）单纯照射组（10.8±1.49）和治疗组（8.53±1.55）较健康对照组（5.83±0.45）明显升高（F=23.20，P<0.05），但治疗组较单纯照射组减小（P<0.05）。病理组织学变化3个月时主要为肺组织的变性、坏死及炎细胞浸润伴成纤维细胞及局灶性纤维增生；4个月时肺泡及间质炎减轻，而纤维增生及胶原沉积则愈加明显，但治疗组的病理变化均较单纯照射组为轻。组织学评分肺泡炎在3个月时单纯照射组、治疗组均与健康对照组存在差异（F=11.93，P<0.05），纤维化评分在3、4个月时相点单纯照射组、治疗组均较健康对照组升高（F=28.73、16.85，P<0.05），但治疗组较单纯照射组降低，4个月时存在差异（P<0.05），天狼猩红染色结合图像分析测定胶原含量（IOD值）4个月较3个月升高，3、4个月单纯照射组各为4 653±1 018、11 174±1 999，治疗组为2 380±314、6 687±661，较健康对照组的251±54、2 001±264明显升高（F=17.70、17.79，P<0.05），但治疗组升高程度较单纯照射组明显降低（P<0.05）。结论 采用照射前G-CSF行自体干细胞动员可减轻放射性肺损伤，降低死亡率，提示其对放射性肺损伤的防治具有正向作用。 |
| 英文摘要: |
| Objective To investigate the effects of G-CSF-mobilized autologous stem cells in the prevention of radiation pulmonary injury. Methods Mice were divided into control group, irradiation group and treatment group. Mouse model of pulmonary fibrosis was established by exposing chest to a single dose of 14 Gy. Animals in the treatment group received recombinant human G-CSF (250 μg/kg daily for 5 d) before the irradiation in order to mobilize autologous stem cells in vivo. The general condition and mortality were documented after radiation injury. The pathological study with histological scoring, Masson staining and Sirius red staining with polarized light analysis were used to identify lung injury and the potential benefit of stem cell mobilization. Results Local chest irradiation of a single dose of 14 Gy was a suitable dose to create radiation-induced pulmonary fibrosis in mice. The death rate was 37.5%, which mainly happened around 11 weeks after injury. In contrast, all of the animals in G-CSF treated group survived. The ratio of lung to body mass was significantly increased in both irradiation group and treatment group (F=23.20,P<0.05) around 3 months after the injury, with a higher ratio in irradiation group than that in treatment group (P<0.05). Histological scoring for alveolar inflammation at 3 months after injury revealed statistically significant difference in irradiation group and treatment group compared with control group (F=11.93,P<0.05). At this time point, the pathological observation showed lung tissue degeneration and necrosis with alveolitis and interstitial inflammation, as well as fibroblasts proliferation and focal collagen deposition in alveolar septa. At 4 month after the injury, the inflammation in interstitial tissue was receded, but fibrosis and collagen deposition were significantly increased. In addition, at 3 and 4 months after injury, the pulmonary fibrosis was aggravated in irradiation group(F=28.73, 16.85, P<0.05), and significantly alleviated in the treatment group (P<0.05). The similar results were confirmed in collagen content analysis (IOD) by Sirius red staining and image analysis (F=17.70, 17.79,P<0.05). Conclusions Autologous mobilization of stem cells could prevent the death of radiation-injured animals possibly by alleviating early lung injury and interstitial inflammation as well as the late pulmonary fibrosis, suggesting a therapeutic potential of autologous stem cell mobilization in radiation pulmonary fibrosis. |
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