Janus激酶2在实验性重症急性胰腺炎肝损伤中的作用

Role of Janus kinase 2 in liver injury in experimental severe acute pancreatitis

目的观察Janus激酶/信号转导和转录激活因子（JAK/STAT）信号通路的核心分子Janus激酶2（JAK2）在实验性重症急性胰腺炎（SAP）肝损伤中的表达变化。方法以4%牛磺胆酸钠胰胆管逆行注射诱导大鼠SAP模型。32只雄性SD大鼠随机分为4组：对照组（NC组）和SAP6h、12h、18h组,每组8只。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）水平;光镜下观察肝脏组织病理变化;免疫组化及Western blotting法检测JAK2在肝组织中的蛋白表达水平变化。结果与NC组比较,SAP各组AMY、ALT、AST水平均明显升高（P〈0.05）,光镜下肝脏组织损伤随病情进展而逐渐加重,SAP后6h有少量JAK2蛋白表达,12～18h达高峰（P〈0.05）,且JAK2表达与肝损伤的严重程度相一致。结论JAK2蛋白在SAP发生时高表达,参与SAP形成的病理过程,JAK/STAT通路活化可能促进SAP肝损伤。

Objective To investigate the expression of Janus kinase 2 （JAK2） in liver injury subsequent to experimental severe acute pancreatifis （SAP）. Methods The rat model of SAP was reproduced by retrograde infusion of 4% sodium taurocholate into the biliopan- ereafic duet. Thirty-two male SD rats were randomly assigned into 4 groups （8 each） ： normal control group （NC）, SAP 6h, 12h and 18h groups. Serum levels of amylase （AMY）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured. The pathologic changes in liver were observed under the light microscope. Immunohistochemistry and Western blotting were used to detect the expression of JAK2 proteins in rat liver. Results In each SAP group, serum level of AMY, AST and ALT increased significantly compared with that of NC group （P〈0. 05）. Based on the microscopic observation, it was found that the liver injury was aggravated gradually with progression of the disease. The expression of JAK2 protein increased slightly at SAP 6h, and reached the peak value at SAP 12-18h. The expression of JAK2 protein in liver paralleled to the severity of liver injury. Conclusiom Severe acute pancreatitis could result in high expression of JAK2 proteins in liver, and it plays an important role in the pathogenesis of severe acute pancreafitis. The activation of JAK/ STAT signaling pathway may probably promote liver injury of severe acute pancreatitis in rats.