选择性一氧化氮合成酶抑制剂对脑组织保护作用研究

Study of neuroprotective effect of a selective inhibitor of nitric oxide synthetase after traumatic brain injury

目的 探讨创伤性脑损伤后脑组织中一氧化氮 (NO)含量变化与脑组织病理及超微结构变化之间的关系 ,及选择性一氧化氮合成酶抑制剂 (iNOS) 14 0 0W (N [3 (aminomethyl)benzyl]acetamidine)对脑组织的保护作用。方法 114只大鼠随机分成正常组、假手术组、生理盐水治疗组和14 0 0W治疗组 ,建立大鼠自由落体脑外伤模型 ,伤后 18h开始分别给予生理盐水和 14 0 0W腹腔内注射 ,每 8h一次。测定各组不同时期脑组织NO含量 ,同时观察脑组织病理及超微结构的改变 ,将结果进行比较。结果 生理盐水治疗组NO含量于伤后 6h开始升高 ,4 8h达到高峰 ,以后逐渐下降。14 0 0W治疗组NO含量降低 ,与生理盐水治疗组结果比较有统计学意义 ,72h后逐步恢复正常。生理盐水治疗组组织病理学检查和超微结构检查结果与NO改变同步 ,14 0 0W治疗组较生理盐水治疗组明显改善。结论 NO对脑外伤后继发性损伤起着重要作用 ,14 0

Objective To study the relationship between NO levels and histopathological and ultrastructural changes in rat brain after experimental traumatic brain injury, and to investigate the protective effect of 1400W (N [3 (aminomethyl)benzyl]acetamidine),a selective inhibitor of inducible nitric oxide synthetase, on the traumatic brain tissue. Methods One hundred and fourteen male SD rats were randomly divided into the following groups: normal group, sham operation group, saline solution treatment group and 1400W treatment group. The brain injury model of the rat was made with free dropping impact. The treatment with 1400W or saline solution was initiated at 18 h after trauma and went on intraperitoneal injections at 8 h interval. The concentrations of NO at different time were determined in the treated group and the control group, while the histopathological and ultrastructureal changes were observed. The experimental results were compared in the two groups. Results NO levels in the control group increased significantly after trauma, and reached the peak at 48 h then decreased gradually . In the treated group, the level of NO decreased significantly and returned to normal level gradually after 72 h. Histopathological and ultrastructural outcomes accorded with NO levels in the saline solution treatment group, while 1400W improved significantly it. Conclusion NO plays an important role in the secondary insults after traumatic brain injury. 1400W has an obviously protective effect on the post traumatic brain tissue.