JAK2/STAT3信号通路在应激性溃疡大鼠胃黏膜炎症反应中的作用研究

目的：探讨Janus激酶2（JAK2）/信号转导与转录激活子3（STAT3）信号通路在应激性溃疡（SU）的胃黏膜炎症反应过程中的作用。方法：选用雄性清洁级SD大鼠96只,随机分为4组,分别为：正常对照组（NC组）、应激性溃疡组（SU组）、抑制剂组（AG490组）、二甲基亚砜组（DMSO组）。建立水浸束缚SU大鼠模型。4组大鼠分别于实验开始后2h、4h、8h、16h各取6只,测定胃黏膜血流量（GMBF）,计算溃疡指数（UI）。观察胃黏膜组织学变化,测定TNF-α、IL-1β、IL-6以及JAK2、p-JAK2、STAT3、p-STAT3的表达量。结果：SU组GMBF明显低于NC组,而UI明显高于NC组（P〈0.01）;AG490组GMBF明显高于SU组,而UI明显低于SU组（P〈0.01）。通过造模前给予抑制剂AG490,胃黏膜病理学变化明显改善。SU组TNF-a、IL-1β、IL-6以及p-JAK2、p-STAT 3表达量明显高于NC组（P〈0.01）,而AG490组较SU组显著降低（P〈0.01）。结论：JAK2/STAT 3信号通路参与了SU大鼠胃黏膜炎症反应过程,使用JAK2特异性抑制剂AG490可以减轻SU大鼠胃黏膜炎症反应。

Role of JAK2/STAT3 signaling pathway in the gastric mucosal inflammation response of rats with stress ulcer

Objective：To investigate the role of JAK2/STAT3 signaling pathway in gastric mucosal inflammation response of rats with stress ulcer（SU）.Method：96male SD rats of clean grade were randomly（random number）divided into four groups which include normal control group（NC group）,stress ulcer group（SU group）,inhibitor group（AG490group）,dimethyl sulfoxide group（DMSO group）.The SU rat model of water immersion restraint was established.Four groups of rats were respectively taken 6on 2h,4h,8h,16 hafter the beginning of experiment.Gastric mucosal blood flow was measured and ulcer index（UI）was calculated.Then,we observed the histological changes of gastric mucosa and measured the expression of TNF-α,IL-1β,IL-6,JAK2,p-JAK2,STAT3 and p-STAT3.Result：GMBF and UI of SU group was significantly lower than that of the NC group（P〈0.01）,while GMBF and UI of AG490 group was significantly higher than that of SU group（P〈0.01）.When inhibitor AG490 was given before modeling,pathological changes of gastric mucosa was significantly improved.The expression of TNF-α,IL-1β,IL-6,p-JAK2 and p-STAT3 in SU group rats were significantly higher than that of NC group（P〈0.01）,while that of AG490 group was significantly lower than that of SU group（P〈0.01）.Conclusion：JAK2/STAT3 signaling pathways is involved in the gastric mucosa inflammation response of SU rats.AG490,a JAK2 specific inhibitor,can reduce the gastric mucosal inflammation response of SU rats.