黄体酮对脑梗死大鼠血脑屏障保护作用的机制研究

Mechanism of the protective effect of progesterone on blood brain barrier in rats with cerebral infarction

目的观察黄体酮对大脑中动脉栓塞（MCAO）大鼠脑部炎症反应的抑制作用以及对血脑屏障结构的影响。方法健康雄性SD大鼠按照完全随机数字表法分为4组，即假手术组、缺血组、溶剂治疗组和黄体酮治疗组。后三组采用线栓法制作MCAO大鼠模型，假手术组只分离、暴露血管，不结扎动脉，不插入尼龙鱼线；黄体酮治疗组造模成功后腹腔注射黄体酮，溶剂治疗组给予等体积的环糊精溶液治疗。Westernblot检测梗死半球脑组织内TNF—α与血脑屏障紧密连接蛋白主要成分Claudin5的表达情况，并通过干湿重法检测脑组织含水量的变化。结果脑梗死发生后，脑部TNF-α的表达水平明显升高，Claudin5蛋白的表达水平明显下降。黄体酮治疗后，梗死半球脑组织内TNF-α的表达水平明显下降，Claudin5蛋白的丢失减少，脑组织含水量亦下降。结论黄体酮可以通过抑制脑梗死大鼠脑部的炎症反应，减轻血脑屏障的破坏，进而发挥神经保护作用。

Objective To investigate the inhibitory effects of progesterone on the inflammatory response and its influence on the structure of the blood brain barrier （BBB） of rats after cerebral infarction. Methods Progesterone was injected intraperitoneally following permanent middle cerebral artery occlusion （MCAO） in rats. Western blotting was used to detect the expressions of tumor necrosis factor-alpha （TNF-α and claudin-5, the major component of tight-junction proteins associated with the BBB. The water content in the injured brain tissue was also examined. Results The expression level of TNF-α increased but claudin-5 expression decreased in the brain tissue of all the rats following MCAO. Progesterone treatment significantly reduced the TNF-α expression in comparison with the vehicle-treated rats, resulting also in ameliorated claudin-5 protein loss and reduced water content in the injured brain tissue. Conclusion Progesterone inhibits the inflammatory response and mitigates the brain damage after cerebral infarction in rats, suggesting the role of this steroid as a neuroprotective agent.