Cui Yu-fang, Ding Yan-qing, Zhang Ying, Xu Han, Jin Wei, Liu Xiao-lan, Dong Bo, Mao Jian-ping, Mao Bing-zhi
Department of Immunology, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2005 Feb;17(2):109-12.
OBJECTIVE: To observe the apoptotic characteristics of mouse spleen lymphocyte after lethal dose gamma-irradiation and its relationship to the expression of Bax and Bcl-XL proteins. METHODS: Two hundred and twenty-five second-grade C57 mice were randomly divided into six groups of 0, 6, 9, 12, 15 and 20 Gy. They were sacrificed by dislocation and samples were taken on 1-28 days after whole body single gamma-irradiation. Lymphocyte apoptosis and necrosis were analyzed by TdT-mediated dUTP nick end labeling (TUNEL) and flow cytometry (FCM) techniques. The expression of Bax and Bcl-XL proteins were estimated by immunohistochemical method. RESULTS: (1) The number of peripheral white blood cells of mice increased temporarily at 6 hours after radiation, thereafter, began to decrease rapidly, which reached the minimum on day 7 and recovered normal level basically one month after 6 Gy gamma-irradiation. (2) Apoptotic rate of spleen lymphocytes increased significantly, peaking at 6 hours after radiation, which was found to have a dose-response relationship during 6-24 hours after < or =12 Gy irradiation, but decreased after > or =15 Gy irradiation. (3) It was confirmed by FCM that the apoptotic rate of spleen lymphocytes increased along with the elevation of radiation dose. However, the apoptotic rate began to decrease and the necrotic rate rose distinctively after > or =15 Gy irradiation. The analysis of DNA gel electrophoresis supported above-mentioned results. (4) The expression of Bax protein in spleen lymphocyte enhanced at 6 hours after 6 Gy gamma-irradiation and peaked by 12 Gy-irradiation, showing a dose-dependent pattern, but which was not be found after > or =15 Gy gamma-irradiation. On the other hand, the expression of Bcl-XL protein reduced persistently with the increase of radiation dose, and also presented a better dose-dependent effect after < or =12 Gy irradiation. CONCLUSION: After 6-12 Gy gamma-irradiation, the apoptosis is the major death way of spleen lymphocyte, while both necrosis and apoptosis are important death pathways after > or =15 Gy irradiation. Pro-apoptotic Bax and anti-apoptotic Bcl-XL play an important role in the apoptotic regulation of spleen lymphocytes induced by lethal dose radiation.
目的：观察致死剂量γ射线照射后小鼠脾脏淋巴细胞的凋亡特征及其与Bax和Bcl-XL蛋白表达的关系。 方法：将225只二级C57小鼠随机分为0、6、9、12、15和20 Gy六组。经全身单次γ射线照射后1至28天，通过脱臼法处死小鼠并取材。采用TdT介导的dUTP缺口末端标记法（TUNEL）和流式细胞术（FCM）技术分析淋巴细胞凋亡和坏死情况。用免疫组织化学方法检测Bax和Bcl-XL蛋白的表达。 结果：（1）小鼠外周血白细胞数在照射后6小时暂时升高，此后开始迅速下降，6 Gy γ射线照射后第7天降至最低，1个月后基本恢复正常水平。（2）脾脏淋巴细胞凋亡率显著升高，在照射后6小时达到峰值，在≤12 Gy照射后6至24小时呈剂量反应关系，但在≥15 Gy照射后下降。（3）FCM证实脾脏淋巴细胞凋亡率随照射剂量升高而增加。然而，在≥15 Gy照射后凋亡率开始下降，坏死率明显上升。DNA凝胶电泳分析支持上述结果。（4）6 Gy γ射线照射后6小时脾脏淋巴细胞中Bax蛋白表达增强，12 Gy照射时达到峰值，呈剂量依赖模式，但在≥15 Gy γ射线照射后未发现。另一方面，Bcl-XL蛋白表达随照射剂量增加持续降低，在≤12 Gy照射后也呈现较好的剂量依赖效应。 结论：6至12 Gy γ射线照射后，凋亡是脾脏淋巴细胞的主要死亡方式，而≥15 Gy照射后坏死和凋亡均为重要死亡途径。促凋亡的Bax和抗凋亡的Bcl-XL在致死剂量辐射诱导的脾脏淋巴细胞凋亡调控中起重要作用。
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