Effect of JAK2/STAT3 signaling pathway on liver injury associated with severe acute pancreatitis in rats
Effect of JAK2/STAT3 signaling pathway on liver injury associated with severe acute pancreatitis in rats
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DOI：
10.3892/etm.2018.6433
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发表时间：
2018-09-01
影响因子：
2.7
通讯作者：
Wang, Fangyu
中科院分区：
文献类型：
--
作者：
Li, Minli;Zhang, Xiaohua;Wang, Fangyu
Janus激酶/信号转导和转录激活因子（JAK/STAT）信号转导是细胞因子信号转导的主要途径之一。然而，JAK 2/STAT 3通路在重症急性胰腺炎（SAP）肝损伤中的作用仍不清楚。本研究旨在探讨JAK 2/STAT 3信号通路在SAP后肝损伤中的作用。在本研究中，将64只雄性Sprague-Dawley大鼠随机分为四组：对照组、AG 490（JAK 2抑制剂）组、SAP组和SAP + AG 490组。胰胆管逆行灌注4%牛磺胆酸钠诱发SAP。测定血清淀粉酶（AMY）和肝酶活性。分离肝脏和胰腺用于测量组织学损伤。取血液和肝脏样品用于测量TNF-α、IL-6和IL-18浓度。采用免疫组化和Western blotting方法检测肝组织JAK 2和STAT 3的表达水平。结果表明，SAP组的淀粉酶和肝酶高于对照组、AG 490组和AG 490处理组。SAP组血清TNF-α、IL-6和IL-18水平明显升高，而AG 490组血清TNF-α、IL-6和IL-18水平明显降低。有趣的是，JAK 2和STAT 3蛋白表达水平在SAP诱导后显著增加，并且在AG 490预处理组中显著降低。给予AG 490可降低SAP大鼠促炎细胞因子的活性，显著减轻SAP相关的肝损伤。提示其作用机制可能与抑制TNF-α、IL-6和IL-18的表达，抑制JAK 2和STAT 3的过度活化有关，在SAP相关肝损伤中起重要作用。
Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling constitutes one of the major pathways for cytokine signal transduction. However, the role of the JAK2/STAT3 pathway in liver injury during severe acute pancreatitis (SAP) remains unclear. The aim of this study was to investigate the role of the JAK2/STAT3 signaling pathway in liver injury after SAP. In the present study 64 male Sprague-Dawley rats were randomly divided into four groups: Control, AG490 (inhibition of JAK2), SAP and SAP with AG490. SAP was induced by retrograde infusion of 4% sodium taurocholate into the biliopancreatic duct. The activities of amylase (AMY) and liver enzymes were measured in serum. Livers and pancreas were isolated for measurements of histological damage. Blood and liver samples were taken for the measurement of TNF-, IL-6 and IL-18 concentrations. The expression levels of JAK2 and STAT3 in liver tissue were detected by immunohistochemical staining and western blotting. The results demonstrated that amylase and liver enzymes were higher in the SAP groups compared with the control, AG490 and AG490-treated groups. The serum levels of TNF-, IL-6 and IL-18 were effectively increased in the SAP groups, whereas they were reduced by AG490. Interestingly, JAK2 and STAT3 protein expression levels were significantly increased following induction of SAP and were significantly decreased in the AG490-pretreated groups. Administration of AG490 decreased the activity of pro-inflammatory cytokines and significantly attenuated SAP associated-liver injury in the rats. These results suggested that the mechanism may relate to the inhibition of TNF-, IL-6 and IL-18, and inhibiting excessive JAK2 and STAT3 activation, and may play a crucial role in the liver injury associated with SAP.