| 常山酮防治放射性肺损伤及其机制的研究* |
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| 引用本文： | 王 鹏, 巩琳琳, 王 帅, 刘宁波, 庞青松, 赵路军, 王 平. 常山酮防治放射性肺损伤及其机制的研究*[J]. 中国肿瘤临床, 2015, 42(6): 323-328. DOI: 10.3969/j.issn.1000-8179.20141969 |
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| 作者姓名： | 王 鹏 巩琳琳 王 帅 刘宁波 庞青松 赵路军 王 平 |
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| 作者单位： | 作者单位:天津医科大学肿瘤医院放疗科,国家肿瘤临床医学研究中心,天津市肿瘤防治重点实验室(天津市300060) |
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| 摘 要： | 目的：研究常山酮对放射性肺损伤的防治作用，并探索其可能机制。方法：健康雌性C 57BL/6J 小鼠72只，随机分为对照组、照射组、常山酮组及照射联合常山酮组，每组18只。对照组不做处理；常山酮组每只小鼠予常山酮灌胃1 次/d ，连续1 个月或至处死；联合组灌胃方法同常山酮组，并于灌胃至15d 时予全肺6MV-X 线单次照射12Gy；照射组予全肺照射，照射时间及剂量同联合组；照射后24h 、1 、2 、4 、12、20周各组随机处死3 只，留取肺组织，H&E染色观察肺组织形态、羟脯氨酸碱水解法测定羟脯氨酸含量、免疫组织化学法及RT-PCR 法测定TGF-β 1 的表达水平。结果：H&E染色结果示联合组小鼠各时间点肺泡炎症及（或）肺纤维化程度较照射组均明显减轻。联合组肺组织羟脯氨酸含量低于照射组，至照射后20周达统计学差异（P =0.037）。 免疫组织化学及RT-PCR 结果示照射后各时间点照射组及联合组肺组织中TGF-β 1 表达水平均高于对照组及常山酮组（均P < 0.05）；联合组TGF-β 1 蛋白表达水平于照射后2、4、12、20周显著低于照射组（均P < 0.05），TGF-β 1 mRNA 水平于照射后4、12周显著低于照射组（均P < 0.05）。 结论：常山酮可抑制胸部照射后小鼠肺组织炎性及纤维化改变，这可能是通过抑制放射导致的肺组织中TGF-β 1 表达升高引起的，有望将常山酮开发为防治放射性肺损伤的新型药物。
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| 关 键 词： | 常山酮 转化生长因子- β 1 放射性肺损伤 羟脯氨酸 |
| 收稿时间： | 2014-11-22 |
| 修稿时间： | 2015-01-15 |
Study of halofuginone in ameliorating radiation injury of lung |
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| Peng WANG, Linlin GONG, Shuai WANG, Ningbo LIU, Qingsong PANG, Lujun ZHAO, Ping WANG. Study of halofuginone in ameliorating radiation injury of lung[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2015, 42(6): 323-328. DOI: 10.3969/j.issn.1000-8179.20141969 |
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| Authors: | Peng WANG Linlin GONG Shuai WANG Ningbo LIU Qingsong PANG Lujun ZHAO Ping WANG |
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| Affiliation: | Department of Radiation Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China |
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| Abstract: | Objective:To investigate the inhibitory effects of halofuginone on radiation-induced pulmonary injury and to explore the therapeutic mechanism of this drug. Methods:A total of 72healthy female C 57BL/6 mice were randomized into4 groups, namely, control, irradiation, halofuginone, and irradiation plus halofuginone groups, with 18mice in each group. No treatment was performed in the control group. In the halofuginone group, the halofuginone lavage was conducted once a day, with a continuous course treatment for a month or until sacrifice of the mice. In the therapeutic alliance group, the treatment mode was the same as that in the halofuginone group. Then, a 6MV-X ray single fraction irradiation was performed after the completion of a15-day intragastric administration. At 24h, 1 week,2 weeks, 4 weeks, 12weeks, and 20weeks after the irradiation, 3 mice from each group were randomly sacrificed, and total lung tissues were harvested. The lung was dissected to prepare pathological sections. The sections were stained with hematoxylin and eosin staining (H&E) to explore morphologic changes. The protein and mRNA expression levels of TGF- β 1 were analyzed by a combi-nation of immunohistochemistry and polymerase chain reaction. The level of hydroxyproline was also measured.Results: The out-comes of H&E staining showed that halofuginone markedly ameliorated the acute pulmonary inflammation and fibrosis induced by irra -diation. The combination group had a lower level of hydroxyproline than the irradiation group, with statistically significant differences at 20weeks after irradiation (P=0.037). The protein and mRNA expression levels of TGF-β 1 were higher in the irradiation and combi-nation groups than in the control group and (or) halofuginone group at different time points (P<0.05). The combination group had lower TGF-β 1 protein expression than the irradiation group at different time points, with statistically significant differences at 2, 4, 12, and 20 weeks after the irradiation (P<0.05). Meanwhile, TGF-β 1 mRNA level was lower in the combination group than in the irradiation group only at 4 and 12weeks after the irradiation (P<0.05). Conclusion:Halofuginone can ameliorate the irradiation-induced lung inflammation and fibrosis probably by inhibiting the radiation-induced TGF- β 1 expression. Therefore, halofugione is expected to be a therapeutic drug for preventing irradiation injury of the lung. |
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| Keywords: | halofuginone transforming growth factor- β 1 radiation injury of lung hydroxyproline |
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