黄体酮对大鼠脑外伤后皮层Toll样受体和核因子-kB表达的影响

Progesterone administration modulates expressions of toil-like receptors and NF-kB after traumatic brain injury in male rats

目的探讨黄体酮对创伤性脑损伤（traumatic brain injury，TBI）后脑皮层中Toll样受体（toll—likereceptors，TLR）和核因子-kB（nuclear factor—kappa B，NF—kB）表达的调控作用。方法雄性Wistar大鼠18只，随机分为对照组、创伤组和黄体酮治疗组，采用自由落体撞击致重型颅脑损伤，黄体酮注射剂量为16mg／kg，连续注射5d，伤后第5天处死动物，取脑挫裂伤周围区脑皮层标本，分别测定TLR2、TLR4的mRNA表达和NF—kB结合活性。结果与对照组相比，创伤组TLR2、TLR4的mRNA水平和NF—kB活性明显上调（P〈0．01）；黄体酮治疗组中，TLR2、TLR4和NF—kB活性显著下降（P〈0．01）。结论 黄体酮能够抑制TBI后皮层中TLR2、TLR4和NF—kB的表达，这可能是黄体酮实现神经保护作用的机制之一。

Objective To investigate the role of progesterone in regulating expressions of toll-like receptors （TLR） and nuclear factor-kappa B （NF-kB） in the injured brain following traumatic brain injury （TBI）. Methods A total of 18 male Wistar rats were randomly divided into control group, trauma group and progesterone treatment group. Right parietal cortical contusion was made by using weight-dropping method. Rats were injected with 16 mg/kg progesterone at 1 and 6 hours and at days 1,2, 3,4 and 5 after TBI. Rats were sacrificed to extract brain samples at day 5 after trauma for measuring mRNA expressions of TLR2 and TLR4 as well as NF-kB binding activity. Results TBI could up-regulate mRNA levels of TLR2 and TLR4 and activity of NF-kB in the contusion area （P 〈0.01 ）. But, administration of progesterone following TBI exerted a contrary effects, ie, down-regulation of level of TLR2 and TLR4 and activity of NF-kB （P 〈 0.01 ）. Conclusion Progesterone may attenuate expressions of TLR2, TLR4 and NF-kB in the injured rat brain, as may be one of mechanisms that progesterone attains neural protection following TBI.