急性胰腺炎发病过程中肿瘤坏死因子受体p55/p75的表达及意义

Expression of tumor necrosis factor receptor p55/p75 and its significance in pathogenesis of acute pancreatitis.

目的探讨肿瘤坏死因子受体p55/p75(TNFR-p55/TNFR-p75)在实验性急性水肿型胰腺炎(AEP)发病机制中的作用。方法36只雄性SD大鼠随机分为对照组与AEP组。AEP组采用雨蛙肽(20μg/kg体重)腹腔注射,每小时1次,共4次建立大鼠急性水肿型胰腺炎模型,对照组仅给予腹腔注射生理盐水。两组大鼠分别在造模后3、6、12 h处死,收集外周血与胰腺标本。应用ELISA法检测血清TNF-α水平,运用RT-PCR的方法检测外周血单核细胞(PBMC)与胰腺组织中TNFR-p55/TNFR- p75mRNA表达,同时测定血清淀粉酶与病理组织学评分作为急性胰腺炎严重程度的指标。结果MAP组3个时间点血清淀粉酶、TNF-α水平及胰腺组织炎症评分均显著高于对照组(P<0.01),在PBMC及胰腺组织中TNFR-p55/TNFR-p75 mRNA的表达均显著上调(P<0.05)。结论TNF-α是急性胰腺炎病程中的重要细胞因子并通过结合胰腺组织中TNFR-1355、TNFR-p75参与引起胰腺组织损伤;同时TNF-α通过与PBMC中TNFR-p55/TNFR-p75相互作用导致外周血中白细胞活化,从而影响急性胰腺炎的严重程度。

Objective The aim of this study is to clarify the role of tumor necrosis factor receptor-p55/p75 （TNFR-p55/TNFR-p75） in the pathogenesis of acute edematous pancreatitis （AEP）. Methods Thirty-six male Sprague-Dawley rats were randomly divided into 2 groups： AEP group and control group. The AEP animals received intraperitoneal injections of caerulin（20 μg/kg body weight）, repeated 4 times every hour, while the control animals were given intraperitoneal injections of physiological saline solution only. All rats were sacrificed at 3, 6, and 12 hours after the AEP model was established. Blood samples and pancreatic tissues were harvested. The severity of pancreatitis was assessed according to serum amylase levels and histological scoring. The serum level of tumor necrosis factor alpha （TNF-α） was examined by ELISA. The expression of TNFR-p55mRNA and TNFR- p75mRNA in pancreatic tissues and peripheral blood mononuclear cells （PBMC） was measured by semiquantitative RT-PCR. Results Both serum amylase and TNF-α alevels of the AEP group were significantly higher than those of the control group at each time point （P 〈 0.01 ）. The expression of TNFR-p55 mRNA and TNFR-p75 mRNA in both PBMC and pancreatic tissues of the MAP group were significantly up-regulated at each time point （P 〈 0.05）. Conclusions TNF-α is a pivotal factor in the pathogenesis of pancreatitis and its binding to TNFR-p55 and TNFR-p75 may initiate the pathological deterioration of pancreatic tissue. The present study also suggests a pathogenetic role of cytotoxic TNF pathway in the clinical features of MAP by enhancing leucocyte activation through up-regulation of TNFR-p55 and TNFR-p75 in both PBMC and pancreatic tissue.