SOCS3在实验性急性胰腺炎急性肺损伤大鼠肺组织中的表达和作用

摘要

背景:细胞因子信号转导抑制分子3(SOCS3)在多种疾病的各种器官损伤中起重要的调节作用,可通过对JAK/STAT信号通路的负反馈作用调节炎症因子的释放,从而起一定的抑炎作用.目前关于SOCS3在重症急性胰腺炎(SAP)急性肺损伤中的表达和作用尚未见报道.目的:探讨SOCS3在实验性急性胰腺炎(AP)合并急性肺损伤大鼠肺组织中的表达变化及其可能的作用.方法:32只Sprague-Dawley大鼠随机分为对照组和AP6 h、12 h、18h组.以4％牛磺胆酸钠胰胆管逆行注射诱导AP模型.动态测定各组血清淀粉酶(AMY)水平、肺湿/干重比；光学显微镜下观察肺组织学表现；ELISA法检测血清白细胞介素(IL)-6、IL-18含量;免疫组化法和蛋白质印迹法检测肺组织中SOCS3的定位和表达.结果:与对照组相比,各AP模型组血清AMY水平、肺湿/干重比均明显升高(P＜0.05);肺组织损伤随病情进展而逐渐加重;血清IL-6、IL-18水平显著上调(P＜0.05)；肺组织SOCS3表达逐渐增强(P＜0.05),于18h时达高峰.结论:SAP急性肺损伤导致的炎症反应可诱导SOCS3在肺组织中表达,并随着肺组织损伤和炎症反应严重程度的增加而逐渐增高,提示可能与其负反馈调节JAK/STAT信号通路介导的炎症反应的作用存在一定的联系.%Background: Suppressor of cytokine signaling 3 (SOCS3) plays an important regulatory role in organ injuries of many diseases, it can regulate the release of inflammatory cytokines via a negative feedback effect on JAK/STAT signaling pathway and thereby inhibiting inflammation. However, there is no report concerning the expression and role of SOCS3 in severe acute pancreatitis (SAP) associated acute lung injury. Aims: To investigate the expression and role of SOCS3 in rat with experimental acute pancreatitis (AP) associated acute lung injury. Methods: Thirty-two Sprague-Dawley rats were randomly assigned into control group, AP 6 h, AP 12 h and AP 18 h groups. AP model was induced by retrograde injection of 4% sodium taurocholate into pancreatobiliary duct. Serum amylase (AMY) level and wet/dry weight ratio of lung were measured dynamically. Pathological changes of lung were examined under light microscope. Serum levels of interleukin (IL)-6, IL-18 were determined by ELISA. The localization and expression of SOCS3 in lung tissue were determined by immunohistochemical staining and Western blotting. Results: Compared with control group, serum level of AMY, wet/dry weight ratio of lung increased significantly in AP groups (P<0.05), and the lung injuries were gradually aggravated with the progress of disease. Serum levels of IL-6, IL-18 increased significantly (P<0.05) while SOCS3 expression in lung tissues increased gradually (P<0.05) and reached the peak at the 18th hour. Conclusions: Inflammatory response induced by SAP associated acute lung injury can induce the expression of SOCS3 in lung tissue, and the expression increases with the increase in severity of lung injury and inflammatory response. Probably there is some connection with its negative feedback effect on inflammatory response induced by JAK/STAT signaling pathway.