大鼠颅脑损伤后一氧化氮合酶和内皮素的变化及依达拉奉对其的影响

Changes of NOS and ET following craniocerebral trauma in rats and the impact of edaravone

目的观察大鼠颅脑损伤后脑组织中一氧化氮合酶（NOS）和内皮素（ET）含量的变化及依达拉奉对其的影响，并探讨其作用机制。方法将45只SD大鼠随机分为3组，其中正常组5只，麻醉后只行开颅手术，不作头颅打击；治疗组和对照组各20只，采用骨窗形成后硬膜外打击法造成鼠脑挫裂伤模型，治疗组致伤后即刻腹腔内注射5mg／kg依达拉奉，对照组则即刻腹腔内注射等量生理盐水。正常组在伤后1h，对照组和治疗组大鼠分别在伤后1h、6h、12h、24h断头取脑，对大鼠脑外伤后脑组织中NOS和ET含量进行检测。结果（1）治疗组和对照组大鼠脑皮质中的NOS活性在伤后1h较正常组显著升高（P〈0．01），6h开始下降，12～24h降至基础水平。治疗组在伤后1h、6hNOS活性较对照组显著降低（均P〈0.05）。（2）治疗组和对照组大鼠脑皮质中的ET在伤后1-24h较正常组显著升高（P〈0．01）。治疗组在伤后1～24hET较对照组显著降低（ P〈0．05）。结论颅脑损伤后受损脑组织中NOS和ET升高，依达拉奉可通过抑制损伤后NOS和ET起到保护创伤神经元的作用。

Objective To observe the changes of nitric oxide synthase （NOS） and endothelin （ET） levels in brain tissues of rats following craniocerebral trauma, and to explore the impact of edaravone （ED） and its mechanism of action. Methods Models with cerebral contusion and laceration were established by extradural hitting following bone window plasty in 45 Spraque-Dawley rats, which were randomly divided into three groups： normal group （n=5）, undergoing craniotomy after anesthesia without cranial hitting or injection; treatment group, intraperitoneally injected with 5 mg/kg ED immediately after hitting, control group, intraperitoneally injected with 5 mg/kg normal saline immediately after hitting. Rats in the control and treatment groups were decapitated and sacrificed respectively at l, 6, 12 and 24 h after hitting and NOS and ET levels in brain tissues following brain trauma were measured. Results （1） The NOS activity in the cerebral cortex of rats was evidently higher than that in the control group at 1 h after hitting （P〈0.01） and began to decrease at 6 h, to the foundation level during 12-24 h. The NOS activity in the ED treatment group was evidently lower than that in the injured group at post-trauma 1 and 6 h （P〈0.05）. （2） The ET level in the cerebral cortex was higher than that in the control group during post-trauma 1-24 h （P〈0.01）. The ET level in the ED treatment group was evidently lower than that in the injured group during post-trauma 1-24 h （P〈0.05）. Conelution NOS and ET levels in brain tissues shall increase following craniocerebral trauma. ED may exert its protective effect on injured neurons through inhibiting NOS and ET levels following trauma.