常山酮防治放射性肺损伤及其机制的研究

发布时间：2018-09-14 08:50

【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C57BL/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15 d时予全肺6MV-X线单次照射12 Gy;照射组予全肺照射,照射时间及剂量同联合组;照射后24 h、1、2、4、12、20周各组随机处死3只,留取肺组织,HE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-β1的表达水平。结果:HE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-β1表达水平均高于对照组及常山酮组(均P0.05);联合组TGF-β1蛋白表达水平于照射后2、4、12、20周显著低于照射组(均P0.05),TGF-β1 m RNA水平于照射后4、12周显著低于照射组(均P0.05)。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-β1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。
[Abstract]:Objective: to study the preventive and therapeutic effects of Changshanone on radiation induced lung injury and explore its possible mechanism. Methods: 72 healthy female C57BL/6J mice were randomly divided into three groups: control group, irradiation group, Changshanone group and combined group with 18 rats in each group. In the control group, the mice in the Changshan ketone group were given intragastric administration of Changshanone once a day for one month or until death, and the combined group was given the same method as the Changshanone group, and the whole lung was irradiated with 6MV-X line for 12 Gy; at the time of gastric perfusion for 15 days. The time and dose of irradiation were the same as those in the combined group, and 3 rats were randomly killed in each group at 24 h after irradiation, 3 rats in each group were sacrificed at random, the lung tissue was stained by HE staining, and the hydroxyproline content was measured by hydrolysation of hydroxyproline. The expression of TGF- 尾 1 was detected by immunohistochemical method and RT-PCR method. Results the grade of alveolar inflammation and / or pulmonary fibrosis in the combined group was significantly reduced than that in the irradiated group. The content of hydroxyproline in the combined group was lower than that in the irradiated group, and the difference was statistically significant at 20 weeks after irradiation (P0. 037). The results of immunohistochemistry and RT-PCR showed that the expression level of TGF- 尾 1 in lung tissue of irradiation group and combination group was higher than that of control group and Changshanone group (P0.05), and the expression level of TGF- 尾 1 protein in combined group was significantly lower than that in irradiation group at 20 weeks after irradiation. The level of TGF- 尾 1 m RNA in group A (P0.05) was significantly lower than that in group B (P 0.05) at 12 weeks after irradiation. Conclusion: Changshanone can inhibit the changes of lung inflammation and fibrosis in mice after chest irradiation, which may be caused by inhibiting the increase of TGF- 尾 1 expression in lung tissue induced by radiation. It is hopeful that Changshanone can be developed as a new drug to prevent and treat radiation-induced lung injury.
【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;
【基金】：国家自然科学基金资助项目(编号:30970864) 天津市抗癌重大专项攻关计划项目(编号:12ZCDZSY15900)资助~~
【分类号】：R730.55

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