姜黄素对Lewis肺癌荷瘤小鼠放疗致机体损伤的保护作用及机制研究

发布时间：2018-01-03 10:05

本文关键词：姜黄素对Lewis肺癌荷瘤小鼠放疗致机体损伤的保护作用及机制研究　出处：《吉林大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的：本研究观察姜黄素对Lewis肺癌荷瘤小鼠的肿瘤放疗增敏及放疗致机体损伤的保护双向作用及其机制研究。方法：C57BL/6纯系小鼠，雌雄各半，，制备小鼠Lewis肺癌体内移植肿瘤模型，按体重将荷瘤小鼠随机分成四组，即空白对照组、单纯放疗组、单纯姜黄素组和姜黄素+放疗联合组。末次给药后称取小鼠体重，测量肿瘤重量及体积，测定各组Lewis肺癌荷瘤小鼠外周血白细胞数量、骨髓有核细胞计数、胸腺及脾指数，同时测定荷瘤小鼠T淋巴细胞转化率、NK细胞杀伤活性及Bax、Bcl-2蛋白表达水平。结果：①与空白对照组比较，单纯放疗组荷瘤小鼠体重、瘤重及肿瘤体积明显降低（P0.05），联合应用姜黄素和放射治疗可使荷瘤小鼠瘤重、肿瘤体积明显降低（P0.01）；与单独放射治疗比较，联合应用可对抗放疗致荷瘤小鼠体重降低（P0.05），且荷瘤小鼠瘤重、肿瘤体积明显下降（P0.05），肿瘤抑制率显著升高（P0.01）；②与空白对照组比较，在Lewis肺癌肿瘤模型中，单纯放疗组在发挥抗肿瘤作用的同时可见脏器指数、外周血白细胞总数及骨髓有核细胞数均明显下降（P0.05或P0.01）；而姜黄素与放射治疗合用可对抗放疗所致的胸腺及脾等免疫器官萎缩、白细胞及骨髓有核细胞数下降，减轻放射治疗所产生的毒性（P0.05或P0.01）；③与空白对照组比较，单纯放疗组ConA诱导的小鼠淋巴细胞增殖反应及小鼠NK细胞活性明显降低（P0.05），姜黄素与放射治疗合用，可使ConA诱导的小鼠淋巴细胞增殖反应显著升高（P0.05），亦可明显提高小鼠NK细胞活性（P0.05）；④与空白对照组比较，单纯放疗组荷瘤小鼠肿瘤组织中Bax蛋白表达量明显升高（P0.01），Bcl-2蛋白表达量明显降低（P0.01），Bax/Bcl-2比率升高（P0.05）；联合应用姜黄素和放射治疗可使荷瘤小鼠Bax蛋白表达量明显升高（P0.01），Bcl-2蛋白表达量明显降低（P0.01），Bax/Bcl-2比率明显升高（P0.05），且作用优于放射治疗组（P0.01）。结论：姜黄素与放射治疗联合应用具有肿瘤放疗增敏作用，还能对正常组织的辐射损伤有保护作用，其机制可能与抗贫血、升高白细胞、免疫调节作用及调节Bax、Bcl-2蛋白表达水平诱导凋亡有关。
[Abstract]:Objective: To observe the effect and mechanism of curcumin on the protective effect of curcumin on radiation sensitization and injury induced by radiotherapy in Lewis lung cancer mice.
Methods: C57BL/6 mice, male and female, the preparation of Lewis lung cancer in mice transplanted tumor model, according to the weight of the tumor bearing mice were randomly divided into four groups: control group, radiotherapy group, pure curcumin group and the curcumin + radiotherapy group. After the last administration said the mice weight, tumor weight and volume measurement, quantitative determination of tumor bearing mice of Lewis lung cancer were peripheral white blood cells, bone marrow nucleated cell count, thymus and spleen index were measured at the same time, the conversion rate of T lymphocytes of tumor bearing mice, NK cell activity and Bax level, the expression of Bcl-2 protein.
Results: compared with control group, radiotherapy group, tumor bearing mice weight, tumor weight and tumor volume decreased significantly (P0.05), the combined application of curcumin and radiation therapy to tumor bearing mice tumor weight, tumor volume decreased significantly (P0.01); compared with radiotherapy alone, radiotherapy combined against induced tumor the body weight decreased (P0.05), and the tumor bearing mice tumor weight, tumor volume decreased significantly (P0.05), the tumor inhibition rate was significantly increased (P0.01); second, compared with the control group, in Lewis lung cancer model, radiotherapy group in play anti-tumor effect and visible organ index, peripheral blood the total cell number and the number of bone marrow nucleated cells were significantly decreased (P0.05 or P0.01); and curcumin and radiotherapy combined with immune organs against radiation-induced thymus and spleen atrophy, white blood cell and bone marrow nucleated cell number decreased, reduce the radiation therapy produced The toxicity (P0.05 or P0.01); and compared with the control group, the activity of lymphocyte proliferation in mice and mouse NK cells induced by ConA irradiation group decreased significantly (P0.05), combination of curcumin and radiation therapy, lymphocyte proliferation reaction induced by ConA can be significantly increased (P0.05), can significantly increase the activity of NK cells mouse (P0.05); and compared with the control group, the expression of Bax protein was significantly higher in the radiotherapy group in tumor tissues (P0.01), Bcl-2 protein expression was significantly decreased (P0.01), the ratio of Bax/Bcl-2 increased (P0.05); combined application of curcumin and radiation therapy to tumor bearing mice Bax protein expression significantly increased (P0.01), Bcl-2 protein expression was significantly reduced (P0.01), Bax/Bcl-2 ratio was significantly increased (P0.05), and the effect is better than that of radiotherapy group (P0.01).
Conclusion: Curcumin combined with radiotherapy can enhance the sensitivity of radiotherapy and protect the radiation injury of normal tissues. The mechanism may be related to anti anemia, increased white blood cells, immunomodulatory effect, and regulate the expression level of Bax and Bcl-2 protein, and induce apoptosis.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R730.5

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