p38MAPK表达在大鼠重症急性胰腺炎肺损伤中的意义

目的 探讨大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)时p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)表达的动态变化及其与肺损伤的关系.方法 72只雄性Wistar大鼠随机分为空白对照组、盐水对照组、胰腺炎组.胰管逆行注射3.5%牛磺胆酸钠诱导莺症急性胰腺炎模型,分别于造模后0.5 h、6 h、12 h、24 h取材.采用免疫组化方法检测肺组织磷酸化p38MAPK活性.利用逆转录一聚合酶链反应(RT-PCR)法检测SAP肺组织p38MAPKmRNA表达,同时观察肺组织病理改变、湿/干重比率及肺组织髓过氧化物酶(myeloperoxidase en-zyme,MPO)等.结果 正常对照组肺组织仅有少量磷酸化p38MAPK活化及p38MAPK mRNA的表达,SAP时肺组织磷酸化p38MAPK及p38MAPK mRNA高表达,MPO活力增加.造模后肺组织p38MAPK mRNA表达明显升高,6 h达高峰,24 h时活性仍高于其基础活性.肺组织p38MAPKmRNA表达与肺损伤病理评分及MPO呈正相关,相关系数分别为0.726,0.629(P<0.01).结论 肺组织p38MAPK活化及过度表达可能是SAP肺损害发生的原因之一.

Significance of expression of p38 MAPK in lung injury in cats with severe acute pancreatitis

Objective To investigate the dynamical changes of p38MAPK activition in the course of SAP and the relationship between the expression of p38MAPKmRNA and pulmonary injury in rats with SAP. Methods Seventy-two Wistar rats were randomized into three groups: the normal group, normal saline group and SAP group. The SAP group was inflicted with 3.5% sodium tauro-cholate by the method of retrograde pancreatic injection. The animals were sacrificed in 0. 5 h, 6 h, 12 h and 24 h after induction of pancreatitis. Activation of p38MAPK in pulmonary tissues was deter-mined with immunohistochemistry. Intrapulmonary expression of p38MAPK mRNA was detected by RT-PCR. Meanwhile, histological grade of lung injury, wet/dry weight ratio and intrapulmonary con-tent of MPO were detected. Results In the normal group, few p38MAPK activity and expression of its mRNA could be detected, which were markedly increased after induction of pancreatitis. There were intrapulmonary overexpression of p38 MAPK mRNA as compared with elevation of intra-pulmo-nary content of MPO. After the SAP was induced, intrapulmonary expression of p38MAPK mRNA was increased obviously, which peaked at 6h and was still higher than basal activity at 24 h point. In-trapulmonary expression of p38 MAPK mRNA had positive correlation with the histological grade of lung injury and intrapulmonary content of MPO (r=0. 726 and 0. 629, P<0. 01). Conclusion The activation and overexpression of p38 MAPK may be one of the reasons for the lung injury in SAP.