摘要
目的探讨JAK2/STAT 3信号通路在实验性重症急性胰腺炎(SAP)肺损伤中的作用。方法以4%牛磺胆酸钠胰胆管逆行注射诱导大鼠SAP模型。32只雄性SD大鼠随机分为4组:对照组(NC组)和SAP 6h、12h、18h组,每组8只。动态测定各组血清淀粉酶(AMY)水平;光镜下观察胰腺及肺组织病理变化,并计算肺湿/干重比;ELISA法检测血清IL-6及IL-18表达情况;West-ern blotting检测肺组织中JAK2和STAT 3蛋白的表达水平。结果与NC组比较,SAP各组AMY水平均明显升高(P<0.01);光镜下胰腺和肺组织损伤随病情进展而逐渐加重;SAP组肺湿/干重比与NC组比较显著升高(P<0.01)。各组血清中均有IL-6及IL-18表达,与NC组比较,SAP各组IL-6及IL-18表达水平均显著上调(P<0.01)。NC组有极少量的JAK2和STAT 3表达,SAP各组JAK2和STAT 3蛋白表达明显高于NC组,且随造模时间延长逐渐增高(P<0.01);JAK2和STAT 3表达变化与肺组织的严重程度一致。结论 JAK2/STAT 3信号通路的激活可诱导IL-6及IL-18过度表达,可能加重SAP时的炎症反应和肺损伤。
Objective To investigate the mechanism of action of JAK/STAT signaling pathways in the lung injury of experimental severe acute pancreatitis(SAP).Methods The rat model of SAP was reproduced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct.Thirty-two male SD rats were randomly assigned into 4 groups(8 each): normal control group(NC),SAP 6h,12h and 18h groups.The level of serum amylase(AMY) was measured dynamically.The pathological changes in pancreas and lung were observed under the light microscope,and the wet/dry weight ratios of lung were evaluated.The concentrations of IL-6 and IL-18 were determined by ELISA,and the expressions of JAK2 and STAT3 protein in lung were determined by Western blotting.Results Compared with NC group,serum level of AMY increased significantly in SAP groups(P0.01),and the pancreas and lung injuries under the light microscope were gradually aggravated with disease progression.The wet/dry weight ratio of lung in SAP groups increased significantly compared with that in NC group(P0.01).The serum concentrations of IL-6,IL-18 in the SAP groups increased significantly compared with those in NC group(P0.01).The concentrations of JAK2 and STAT3 protein in SAP groups increased significantly compared with that in NC group(P0.01) and reached the peak in 12-18 hours.Conclusion Activation of JAK2/STAT3 signaling pathways may induce the over-expressions of IL-6 and IL-18,and aggravate the inflammatory reaction and lung injury induced by SAP.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2011年第6期611-613,共3页
Medical Journal of Chinese People's Liberation Army
基金
南京军区总医院科研基金(2006021)
关键词
信号传导
急性胰腺炎
肺损伤
细胞因子类
signal transduction
acute pancreatitis
lung injury
cytokines