摘要
背景:JAK/STAT细胞内信号通路广泛参与细胞的增殖、分化、凋亡以及炎症、肿瘤的发生等多种生理、病理生理过程,然而关于其在重症急性胰腺炎(SAP)急性肝损伤中作用的研究尚少。目的:观察抑制JAK/STAT通路对实验性急性胰腺炎(AP)大鼠肝损伤的保护作用。方法:56只Sprague-Dawley大鼠随机分为正常对照组、3组AP模型组和3组JAK特异性抑制剂AG490干预组。以4%牛磺胆酸钠胰胆管逆行注射诱导AP模型。分批处死各组大鼠,动态测定血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,观察肝脏大体和组织学表现,以免疫组化染色和蛋白质印迹法检测肝组织中JAK2的定位和表达。结果:与正常对照组相比,AP模型组各时间点血清ALT、AST水平均显著升高;肝组织大体和组织学损伤随病情进展而逐渐加重;肝组织JAK2表达逐渐增强,于18h时达高峰。经AG490预处理的大鼠,上述各项指标均较同时间点AP模型组显著改善。结论:JAK2参与了大鼠实验性AP肝损伤的病理过程,抑制肝组织JAK/STAT通路活化有助于SAP急性肝损伤的防治。
Background： JAK/STAT intracellular signaling pathway is widely involved in many physiologic and pathophysiologic processes, such as cell proliferation, differentiation, apoptosis, inflammation and tumorigenesis, however, few studies have focused on its change in acute liver injury secondary to severe acute pancreatitis （SAP）. Aims： To investigate the protective effect of inhibiting JAK/STAT signaling pathway on liver injury secondary to experimental acute panereatitis （AP） in rats. Methods： Fifty-six Sprague-Dawley rats were randomly divided into normal control group, three AP model groups and three AG490 （a specific inhibitor of JAK） pretreated groups. AP model was induced by retrograde infusion of 4% sodium taurocholate into pancreatobiliary duct. The animals were sacrificed in batches, the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured dynamically, the macroscopic and microscopic changes of liver tissues were examined, and the localization and expression of JAK2 in liver tissues were determined by immunohistochemical staining and Western blotting. Results： Serum levels of ALT and AST at different time points in AP model groups increased significantly as compared with those in normal controls, and the macroscopic and microscopic liver injuries were gradually aggravated with disease progression, JAK2 expression in liver tissues gradually increased and reached the peak in 18-hour group. In AG490 pretreated groups, all the above-mentioned indices improved significantly in comparison with those in the AP model groups at the same time points. Conclusions： JAK2 plays an important role in the pathologic process of liver injury in experimental AP rats. Inhibition of JAFUSTAT signaling pathway in liver tissues is beneficial for the prevention and treatment of acute liver injury secondary to SAP.
出处
《胃肠病学》
2008年第12期719-722,共4页
Chinese Journal of Gastroenterology
