p38丝裂素活化蛋白激酶与细胞外调节蛋白激酶在重症胰腺炎炎症反应和免疫抑制中的作用

目的探讨p38丝裂素活化蛋白激酶（p38 mitogen—activated protein kinase，p38MAPK）与细胞外调节蛋白激酶（extracellular regulated protein kinases，ERK）在重症急性胰腺炎（severe acute pancreatitis，SAP）炎症反应和免疫抑制中的作用。方法75只Wistar大鼠随机分为对照组、SAP组、ERK抑制组（PD组）、p38MAPK抑制组（SB组）、ERK＋P38MAPK联合抑制组（PD＋SB组）各15只。对照组仅作开腹缝合处理，其余4组大鼠建立大鼠SAP模型，其中PD组大鼠术前30min尾静脉注射PD98059，SB组大鼠尾静脉注射SB203580，PD＋SB组大鼠尾静脉注射PD98059与SB203580。术后6、12h观察5组腹腔积液量变化情况。检测5组血清肿瘤坏死因子-α水平，并计算大鼠肺组织湿／干比值。结果对照组腹腔积液量、肺组织湿／干比值及血清肿瘤坏死因子-α水平明显低于其他4组（P〈i0．05），PD＋SB组低于SAP组、PD组和SB组（P〈0．05），PD组和SB组低于SAP组（P〈0．05）。结论ERK、p38MAPK在SAP炎症反应和免疫抑制中发挥重要作用，抑制其活性可抑制SAP过度活化的炎症反应，改善细胞免疫功能低下状态。

Role of p38 mitogen-activated protein kinase and extracellular regulated protein kinases in the inflammatory response and immunosuppression of severe acute pancreatitis

Objective To explore the role of p38 mitogen-activated protein kinase （p38MAPK） and extracellular regulated protein kinase （ERK） in the inflammatory response and immunosuppression of severe acute pancreatitis （SAP）. Methods Seventy-five Wistar rats were randomly divided into control group, SAP group, PD group receiving ERK suppression, SB group receiving p38MAPK suppression, and PD＋SB group receiving ERK and p38MAPK joint suppression, with 15 rats in each group. Control group received only open sutures, and the other 4 groups were established SAP rat models. In 30 minutes before surgery, PD group was injected PD98059, SB group was injected SB203580, and PD＋SB group was injected PD98059 and 8B203580 via the tail vein. The peritoneal fluid changes were determined in 6 and 12 hours after surgery. The serum levels of tumor necrosis factor-α （TNF-α） were detected in 5 groups and the wet/dry ratio in lung tissue was calculated. Results The peritoneal fluid volume, wet/dry ratio and serum levels of TNF-α were significantly lower in control group than those in SAP group, PD group, SB group and PD--SB group （P〈0.05）, in PD＋SB group than those in SAP group, PD group and SB group（P（0.05）, and in PD group and SB group than those in SAP group （P 〈 0.05）. Conclusions ERK and p38MAPK play important roles in the inflammatory response and immunosuppression of SAP, and inhibit SAP overactive inflammatory response by inhibiting the activity so as to improve the state of cellular immune dysfunction.