孕酮对小鼠放射性脑损伤的神经保护作用及分子机制

摘要

Objective To investigate the neuroprotective effects of progesterone on radiation-induced brain injury in mice and its possible molecular mechanism. Methods 144 mice were divided into control group, radiation group and progesterone group. The spatial learning and memory ability of mice were evaluated by Morris water maze test; The water content in brain of mice were measured by dry/wet method; The levels of adenosine triphosphate(ATP), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in cerebrospinal fluid were determined by ELISA. The expression of P2X7 receptor protein in brain tissue was detected by Western blot. Results The average latency time and the length of path of finding platform on fourth to seventh day after training in radiation group were significantly longer than the control group, progesterone group was significantly shorter than that in radiation group (P =0. 000 1). The brain water content and the rate of apoptosis in radiation group were significantly higher than the control group, progesterone group was significantly lower than that of the radiation group (P=0.000 0). The content of ATP, COX-2, TNF-a and IL-6 in cerebrospinal fluid of radiation group were significantly higher than the control group, progesterone group was significantly lower than that in the radiation group (P =0. 010 9, 0. 004 6, 0. 007 8, 0. 001 4 ). The expression of P2X7 receptor protein in brain tissue of radiation group increased significantly compared with the control group, while progesterone group was significantly lower than that of the radiation group. Conclusion Progesterone may inhibit neuropathy caused by radiation-induced brain injury by inhibiting ATP-mediated activation of P2X7 R and release of inflammatory mediators, thereby reducing brain edema and reducing apoptosis.%目的 探讨孕酮对小鼠放射性脑损伤的神经保护作用及其可能分子机制.方法 144只小鼠分为溶剂对照组、单纯照射组和孕酮组,采用Morris水迷宫实验评价小鼠空间学习和记忆能力;干/湿法测定脑含水量;ELISA法检测脑脊液三磷酸腺苷(ATP)、环氧合酶-2(COX-2)、肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)的含量;Western blot法检测脑组织P2X7受体蛋白表达水平.结果 单纯照射组小鼠第4～7天平均潜伏期时间和寻找平台的路径总长均明显大于溶剂对照组,孕酮组明显短于单纯照射组(P=0.0001);单纯照射组脑含水量和细胞凋亡率明显高于溶剂对照组,孕酮组明显低于单纯照射组(P=0. 000 0);单纯照射组脑脊液 ATP、COX-2、TNF-α和IL-6的含量明显高于溶剂对照组,孕酮组明显低于单纯照射组(P=0.010 9、0.004 6、0.007 8、 0.001 4);单纯照射组小鼠脑组织P2X7受体蛋白的表达高于溶剂对照组,而孕酮组P2X7受体蛋白的表达水平明显低于单纯照射组.结论 孕酮可能通过抑制ATP介导的 P2X7R活化和炎症介质的释放,进而减轻脑水肿和减少细胞凋亡,起到保护放射性脑损伤所致的神经损害作用.