帕瑞昔布钠对老年大鼠脾切除术后海马炎症反应及记忆功能的影响

目的：探讨帕瑞昔布对脾切除术后老年大鼠海马炎症反应及短期记忆功能的影响。方法：老年雄性Sprague-Dawley大鼠90只，随机分为9组(均n=10)：空白对照组(C组)、麻醉1 d组(A1组)、手术1 d组(O1组)、生理盐水1 d组(S1组)、帕瑞昔布1 d组(P1组)、麻醉3 d组(A3组)、手术3 d组(O3组)、生理盐水3 d组(S3组)、帕瑞昔布3 d组(P3组)。A1和A3组只接受1%戊巴比妥钠腹腔注射麻醉；O1组和O3组麻醉后行脾切除术；P1组和P3组在手术组基础上术前1 h经尾静脉注射10 mg/kg帕瑞昔布钠；S1组、S3组给予等量生理盐水对照。大鼠行穿梭箱训练5 d后进行麻醉、手术及药物处理。术后1和3 d穿梭箱测试结束后处死大鼠，取海马，分别行CD11b免疫荧光染色，测定TNF-α，IL-1β及环氧合酶-2 (cyclooxygenase-2，COX-2) mRNA的表达。结果：与C组比较，O1和O3组电击时间增加，主动逃避时间缩短，主动回避反应(active avoidance reaction，AAR)降低(均P<0.01)。与O1和O3组比较，P1和P3组电击时间缩短，主动逃避时间增加，AAR提高(均P<0.05)。O1，O3，S1和S3组海马小胶质细胞阳性数目和海马TNF-α，IL-1β及COX-2 mRNA表达明显高于C组(均P<0.01)，但P1，P3组较O1，O3组明显降低(均P<0.01)。结论：帕瑞昔布可能通过抑制COX-2表达而减轻老年大鼠脾切除术后海马炎症反应，提高短期记忆能力。

Effect of parecoxib on hippocampal inflammation and memory function in aged rats after splenectomy

Objective: To explore the effect of parecoxib on hippocampal inflammation and short-term memory function after splenectomy in aged rats. Methods: A total of 90 aged male SD rats were randomly divided into 9 groups (all n=10): a control group (Group C), an anesthesia day 1 group (A1 group), an operation day 1 group (O1 group), a saline day 1 group (S1 group), a parecoxib day 1 group (P1 group), an anesthesia day 3 group (A3 group), an operation day 3 group (O3 group), a saline day 3 group (S3 group), and a parecoxib day 3 group (P3 group). In the A1 group and A3 group, rats were anesthetized by intraperitoneal injection of pentobarbital sodium. Under anesthesia condition, rats in the O1 group and O3 group underwent splenectomy. One hour before splenectomy, rats in the P1 group and P3 group received parecoxib injection of 10 mg/kg via tail vein. In the S1 group and S3 group, rats received the same dose of saline. The rats were trained for 5 days in shuttle box before anesthesia, surgery and drug treatment. After shuttle box test, the rats were killed at postoperative 1 and 3 d. The hippocampus was isolated to measure the CD11b expression by immunofluorescent staining, and TNF-α, IL-1 and COX-2 mRNA expression by RT-PCR. Results: Compared with the Group C, the electric shock time was increased in the O1 and O3 groups, but the active escape time was shortened and the active avoidance reaction (AAR) was decreased (all P<0.01). Compared with the O1 or O3 group, the electric shock time was shortened, the active escape time and AAR was increased in the P1 or P3 group (all P<0.05). There were more CD11b positive cells and TNF-α, IL-1β, COX-2 mRNA expression in hippocampus in the O1, O3, S1 or S3 group compared with the Group C (all P<0.01). Both CD11b positive cells and TNF-α, IL-1β, COX-2 mRNA expression were decreased in the P1 or P3 group compared with that in the O1 or O3 group (all P<0.01). Conclusion: The parecoxib could reduce hippocampal inflammation and improve short-term memory function through the inhibition of COX-2 expression in aged rats after splenectomy.