塞来昔布对大鼠重症急性胰腺炎血清TNF-α,IL-1β,IL-6及IL-8水平的影响

Effects of celecoxib on serum proinflammatory cytokines in rats with severe acute pancreatitis

目的:探讨重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠血清促炎性细胞因子TNF-α,IL-1β,IL-6和IL-8的变化及意义,以及应用塞来昔布(celecoxib)的干预效应。方法:胆胰管内注射5%牛磺胆酸钠造模。将动物随机分成对照组、SAP组及塞来昔布组,各组分别于术后3,6,12和24 h 4个时间点处死大鼠,测血清淀粉酶,TNF-α,IL-1β,IL-6和IL-8水平,每次每组5只;取各组术后24 h处死大鼠的胰腺组织,行HE染色,分别观察大鼠胰腺组织病理学变化。结果:对照组胰腺组织基本正常,SAP模型组胰腺腺泡结构严重破坏消失,塞来昔布组病理改变明显减轻;SAP组、塞来昔布组大鼠血清中TNF-α,IL-1β,IL-6和IL-8水平随病程进展而升高(P<0.01),各时相SAP组水平明显高于对照组(P<0.01),塞来昔布组水平明显低于SAP模型组(P<0.01)。结论:TNF-α,IL-1β,IL-6和IL-8与SAP的进展有关,塞来昔布可以减轻SAP的炎症反应,抑制促炎性细胞因子的产生。

Objective： To explore the changes and significance of serum tumor necrosis factor-α（TNF-α）,interleukin-1β（IL-1β）,IL-6 and IL-8 in rats with severe acute pancreatitis（SAP）,and to detect the effect of celecoxib on the changes of these serum cytokines.Methods： The SAP model was established by using retrograde injection of Sodium Taurocholate into cholangiopancreatic duct.Rats in each group were killed 3,6,12 and 24 h（5 rats for each time point） after operation to determine serum levels of amylase,TNF-α,IL-1β,IL-6 and IL-8.The pancreas tissues of the rats 24 h after operation were obtained to examine histopathological changes by HE dyeing.The changes of serum TNF-α,IL-1β,IL-6 and IL-8 in different groups and different time points were detected by ELISA assay.Amylase in serum was detected by automated biochemistry analysis. Results： The pathology of control group was relatively normal.The pathological damage in rats of SAP group was very severely,but celecoxib could ameliorate the pathological damage in rats of SAP group.The levels of serum TNF-α,IL-1β,IL-6 and IL-8 in rats of SAP group were significantly higher than those of control group（P〈0.01） at every time point.Compared to SAP group,the levels of TNF-α,IL-1β,IL-6 and IL-8 were significantly decreased in celecoxib group（P〈0.01）. Conclusion： The cytokines of TNF-α,IL-1β,IL-6 and IL-8 were involved in the pathological injury of SAP.Celecoxib can ameliorate the pathological damage and inhibit the production of proinflammatory cytokine in serum in rats of SAP.