帕瑞昔布对肝部分切除大鼠海马炎症反应的影响及可能机制

Effect of parecoxib on hippocampal inflammation in partial hepatectomy rats and its possible mechanism

目的研究帕瑞昔布对肝部分切除后大鼠海马炎症反应的影响及可能机制。方法选取72只SPF级雄性健康SD大鼠,随机分为对照组(C组)、麻醉组(A组)、手术组(S组)、帕瑞昔布组(P组)4组,每组18只。采用肝部分切除术建立手术创伤致海马炎症动物模型。麻醉后1、3、7 d处死大鼠,检测海马组织炎症介质的表达。采用实时定量PCR检测环氧合酶-2(COX-2)mRNA的表达量,Western blot检测COX-2、半胱氨酸蛋白酶-3(Caspase-3)的蛋白表达量,酶联免疫吸附法(ELISA)检测前列腺素E2(PGE2)的含量。结果与C组相比,A组大鼠海马组织中COX-2表达(蛋白、mRNA),PGE2含量,Caspase-3蛋白表达均差异均无统计学意义;S组、P组大鼠术后第1、3天COX-2,PGE2,Caspase-3表达均明显上调(P<0.05,P<0.01),尤以术后第1天明显(P<0.01),术后第7天上述各炎症指标表达恢复正常。与S组相比,P组术后第1、3天COX-2,PGE2,Caspase-3表达明显下调(P<0.05,P<0.01)。结论肝部分切除术可导致海马炎症反应,帕瑞昔布钠可显著抑制此种炎症反应,其机制可能与下调海马COX-2 mRNA和蛋白表达,降低PGE2含量和Caspase-3蛋白表达有关。

Objective To investigate the effect of parecoxib on hippocampal inflammation following partial hepatectomy in rats.Methods 72 SPF male healthy SD rats were selected and randomly divided into four groups:control group(group C),anesthesia group(group A),operation group(group S),parecoxib group (group P ), each had 18 rats.Using partial hepatectomy operation trauma to establish animal model of hippocampal inflammation.Rats were sacrificed 1,3,7 days after anesthesia,the expression of inflammatory mediators in hippocampal tissue were detected.The expression of cyclooxygenase -2(COX-2)mRNA were detected by real-time quantitative PCR,and COX-2 and cysteine proteinase -3(Caspase-3)protein expression were detected by Western blot,the prostaglandin E2(PGE2)content were detected by enzyme linked immunosorbent assay(ELISA).Results Compared with control group,COX-2 expression(protein and mRNA),PGE2 production and Caspase-3 protein expression in group A had no significant difference.In group S and P,COX-2 expression,PGE2 and Caspase-3 protein expression increased significantly on 1st day postoperatively to 3rd day (P<0.05 or P<0.01),and they were obvious especially in the postoperative 1st day(P<0.01).The above inflammation index expression returned to normal in 7th days after operation.Compared with group S,COX-2 expression,PGE2 and Caspase-3 protein expression increased significantly on 1st day postoperatively to 3rd day(P <0.05 or P <0.01 ).Conclusion Partial hepatectomy could induce hippocampal inflammatory response in the rats.Parecoxib could suppress the hippocampal inflammation via the down-regulation expression of COX-2 mRNA and protein,PGE2 and Caspase-3 protein in rats.