布洛芬通过下调环氧化酶2降低癫痫大鼠海马神经元兴奋性

Ibuprofen reduces the excitability of hippocampal neurons by down-regulating cyclooxygenase 2 in epileptic rats

目的:研究布洛芬对慢性癫痫大鼠海马区环氧化酶2(COX-2)和神经元兴奋性的影响。方法:选用雄性健康SD大鼠48只,随机分为3组,分别为对照组(control)、癫痫组(epilepsy)和治疗组(ibuprofen)。运用戊四氮(PTZ)诱导建立慢性癫痫大鼠模型并用布洛芬干预,采用行为学观察检测大鼠癫痫发作水平,运用免疫组织化学染色和Western Blot技术检测大鼠海马区COX-2的表达情况,运用全细胞膜片钳技术收集并分析大鼠海马区动作电位的变化情况。结果:与对照组相比,癫痫组大鼠癫痫发作明显,海马区COX-2表达升高,海马神经元兴奋性升高(P<0.05);治疗组大鼠癫痫发作等级降低,海马区COX-2表达明显降低,海马神经元兴奋性降低(P<0.05)。结论:布洛芬通过下调COX-2降低癫痫大鼠海马神经元的兴奋性,降低癫痫发作强度,具有一定的保护作用。

Objective: To investigate the effects of ibuprofen on cyclooxygenase 2(COX-2) and excitability of hippocampal neurons in chronic epileptic rats.Methods: Forty-eight healthy male Sprague-Dawley rats were randomly divided into three groups: control group(control),epilepsy group(epilepsy),and ibuprofen treatment group(ibuprofen).Rat model of chronic epilepsy was prepared by intraperitoneally injection of pentylenetetrazol(PTZ).The rats of epilepsy group were treated with ibuprofen.The seizure score of rats was measured by behavioral test.The expression of COX-2 in the hippocampus of rats was detected by immunohistochemical staining and Western Blot.Whole-cell patch-clamp was used to collect and analyze the changes of the action potential in hippocampal neurons.Results:Compared with control group,the seizure score,expression of COX-2 and excitability of hippocampal neurons were significantly increased in the epilepsy group(P < 0.05);The seizure score,expression of COX-2 and excitability of hippocampal neurons in the treatment group were lower than those in the epilepsy group(P < 0.05).Conclusion: Ibuprofen can affect seizures by down-regulating the expression of COX-2 and reducing the excitability of hippocampal neurons in epileptic rats.