SOCS3在重症急性胰腺炎合并肝损伤大鼠肝组织中的表达及意义

Expression and significance of SOCS3 in liver tissue of rats with severe acute pancreatitis complicated by liver injury

目的探讨细胞因子信号转导抑制分子3(SOCS3)在实验性重症急性胰腺炎(SAP)合并肝损伤模型大鼠肝组织中的表达变化及作用机制。方法 32只雄性SD大鼠随机分为对照组(NC组)和SAP 6、12、18h模型组,每组8只。以4%牛磺胆酸钠胰胆管逆行注射诱导SAP模型。动态测定各组血清淀粉酶(AMY)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)的水平;ELISA法测定大鼠血清中IL-6、IL-18的表达情况;免疫组化及Western blotting检测肝组织中SOCS3的定位及表达。结果与NC组比较,SAP各组AMY、ALT、AST水平均明显升高(P<0.05),且各SAP组之间比较差异亦有统计学意义(P<0.05);各组血清中均有IL-6、IL-18表达,与NC组比较,SAP各组IL-6、IL-18表达水平显著上调,各SAP组间差异有统计学意义(P<0.05);NC组有极少量SOCS3表达,SAP各组SOCS3蛋白表达明显高于NC组,且随造模时间延长逐渐升高(P<0.05);SOCS3表达变化与肝组织损伤的严重程度及血清炎症因子的变化一致。结论 SAP合并肝损伤导致的炎症反应可诱导SOCS3在肝组织中的表达,其表达随肝损伤和炎症反应严重程度的增加而升高,可能与其对JAK/STAT信号通路介导的炎症反应负反馈调节作用有关。

Objective To investigate the expression and mechanism of action of suppressor of cytokine signaling 3 （SOCS3） in liver tissue of rats with experimental severe acute pancreatitis （SAP） concurring with liver injury. 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 levels of serum amylase （AMY）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured dynamically. The concentrations of IL-6 and IL-18 were determined by ELISA. The localization and expression of SOCS3 protein in liver were determined by immunohistochemical staining and Western blotting. Results Compared with NC group, the serum levels of AMY, ALT and AST increased significantly in SAP groups （P〈0.05）, and there was significant difference among SAP groups. The serum concentrations of IL-6 and IL-18 increased significantly in the SAP groups than in NC group （P〈0.05）, and there was significant difference among SAP groups. Compared with NC group, the concentration of SOCS3 protein increased significantly in SAP groups, and increased gradually along with the increased duration of pancreatitis （P〈0.05）. A minor expression of SOCS3 protein was found in NC group. The change in SOCS3 protein concentration was consistent with the severity of liver injury as weU as the serum concentrations of IL-6 and IL-18. Conclusions The inflammatory action induced by SAP concurring with liver injury may induce the expression of SOCS3 in liver tissue, and it may increase in intensity along with the severity of liver injury and inflammatory reaction. The mechanism may be attributed to a negative feedback regulation of the inflammatory action mediated by JAK/STAT pathway.