环氧合酶-2抑制剂对创伤后应激障碍大鼠神经功能的改善

Effect of the Cyclooxygenase-2 Inhibitor on Neurological Function of Rats with Post-traumatic Stress Disorder

目的检测创伤后应激障碍(post traumatic stress disorder,PTSD)大鼠海马区环氧合酶-2(cyclooxygenase-2,COX-2)水平和应用COX-2抑制剂塞来昔布(celecoxib)后对大鼠神经功能的改善作用,研究COX-2在PTSD中的可能作用。方法成年雄性大鼠分为正常对照组、PTSD组、COX-2抑制剂治疗组,通过旷场实验、高架十字迷宫实验、水迷宫实验评估大鼠行为能力;通过免疫组织化学染色、RT-PCR与Western blot测量大鼠海马组织COX-2表达情况;ELISA法检测大鼠海马组织白介素-1(interleukin-1,IL-1)、白介素-6(interleukin-6,IL-6)以及前列腺素E2(prostaglandin E2,PGE2)的水平;应用Griess法检测海马组织一氧化氮(nitric oxide,NO)的表达。结果 RT-PCR及Western blot检测显示,治疗组COX-2mRNA及蛋白表达低于模型组而高于正常对照组,差异有统计学意义(均P<0.05),ELISA检测显示治疗组IL-1、IL-6、PEG2含量低于模型组而高于正常对照组,差异有统计学意义(均P<0.05),Griess法检测治疗组NO含量低于模型组而高于正常对照组,差异有统计学意义(均P<0.05),且治疗组较模型组行为学功能得到改善。结论 PTSD大鼠海马中IL-1、IL-6及COX-2的水平升高,同时其下游NO、PGE2的表达增加,推测COX-2是PTSD致病机制中的重要环节,COX-2抑制剂可能通过抑制炎性因子表达改善PTSD大鼠神经功能。

Objective To observe the expression of cyclooxygenase-2（COX-2）in the hippocampi of rats with post-traumatic stress disorder（PTSD）and the protective effect of the COX-2inhibitor（celecoxib）on the neurological function of the rats in order to examine the role of COX-2 in the pathogenesis of PTSD.Methods Adult male Wistar rats were randomly divided into three groups：normal control group,PTSD model group,and COX-2 inhibitor group.The open field test,elevated plus-maze test and water maze test were used to evaluate the rat behaviors.The expression of COX-2 was detected by immunohistochemistry,RT-PCR,and Western blotting,respectively.The levels of interleukin-1（IL-1）,interleukin-6（IL-6）,prostaglandin E2（PGE2）were measured by ELISA and the expression of nitric oxide（NO）by Griess method.Results RT-RCR and Western blotting showed that the expression of COX-2 mRNA and protein was significantly lower in COX-2 inhibitor group than in PTSD model group but still greater in COX-2 inhibitor group than in normal control group,with significant differences found（P0.05 for all）.ELSIA showed that the levels of IL-1,IL-6 and PEG2 were profoundly decreased in COX-2 inhibitor group as compared with PTSD group（P0.05）.The Griess method revealed that the change of NO was similar to that of the indicators mentioned above in the three groups.Behavioral function was greatly improved in COX-2 inhibitor group（P0.05）.Conclusion The levels of IL-1,IL-6 and COX-2 are conspicuously increased and their downstream factors NO and PGE2 are over-expressed in the hippocampi of rats with PTSD,suggesting the involvement of COX-2 in the pathogenesis of PTSD.The COX-2 inhibitor may improve the neurological function of PTSD rats by inhibiting the expression of inflammatory factors.