PI3K/Akt/mTI3K/Akt/mOR信号通路在重症急性胰腺炎致肝脏损伤中的作用  

Role of PI3K/Akt/m TOR Signaling Pathway in Liver Injury Induced by Severe Acute Pancreatitis

作　　者：欧阳军[1] 周跃鲜 李玺[1] 张召辉[1] 牛万成[1] 

机构地区：[1]徐州医学院附属淮海医院普外科,江苏徐州221000 [2]徐州医学院,江苏徐州221004

出　　处：《中国普外基础与临床杂志》2015年第5期555-559,共5页Chinese Journal of Bases and Clinics In General Surgery

摘　　要：目的探讨磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(m TOR)信号通路对重症急性胰腺炎(SAP)致肝脏损伤的影响。方法健康雄性SD大鼠40只,按随机数字表法随机均分为4组(n=10):假手术组、SAP组、PI3K抑制剂LY294002组(简称LY294002组)、m TOR激酶抑制剂rapamycin组(简称rapamycin组)。采用逆行胰胆管注射5%牛磺胆酸钠1 m L/kg方法制备SAP模型。各组大鼠于造模后6 h下腔静脉取血检测血淀粉酶(AMY)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,观察肝脏组织病理学变化,TUNEL法检测肝脏细胞凋亡以计算凋亡指数(AI),Western blot法检测肝脏组织中Akt、磷酸化(p)-Akt、m TOR、p-m TOR蛋白表达情况。结果 1血清AMY、ALT、AST水平及AI:与假手术组相比,其余3组AMY、ALT、AST水平及AI均明显升高(P<0.05);与SAP组相比,LY294002组和rapamycin组这4个指标值均明显降低(P<0.05)。2肝脏组织病理学表现:与假手术组相比,其余3组肝脏组织损伤严重;与SAP组相比,LY294002组和rapamycin组肝脏组织损伤程度有所改善。3 Akt、m TOR、p-Akt、p-m TOR蛋白表达水平:与假手术组比较,其余3组p-Akt/Akt、p-m TOR/m TOR蛋白水平明显升高(P<0.05);与SAP组相比,LY294002组p-Akt/Akt、p-m TOR/m TOR蛋白水平明显降低(P<0.05),rapamycin组p-m TOR/m TOR蛋白水平明显下降(P<0.05),但p-Akt/Akt蛋白水平差异无统计学意义(P>0.05)。结论 PI3K/Akt/m TOR信号通路的激活可能是SAP致肝脏损伤发生的原因之一,抑制该信号通路有可能成为控制SAP发展并减轻肝脏损伤的新途径。Objective To investigate the effect of PI3K/Akt/mTOR signaling pathway on liver injury induced by severe acute pancreatitis （SAP）. Methods Forty healthy adult male Sprague-Dawley （SD） rats were randomly divided into 4 groups： Sham operation group （SO group）, SAP group, PI3K inhibitor LY294002 group （LY294002 group）, and mTOR kinase inhibitor rapamycin group （rapamycin group）. The rat model with SAP was made by injection with 5% sodium deoxycholate through retrogradely bilio pancreatic duct. Serum levels of amylase （AMY）, alanine aminotrans- ferase （ALT）, and aspartate transaminase （AST） were detected through the inferior vena at 6 h after modeling. Pathologic change of the liver was observed under the light microscope. TUNEL analysis was used to detect apoptotic index （AI） of the heptocyte. Expressions ofAkt, phosphated-Akt （p-Akt）, mTOR, phosphated-mTOR （p-mTOR） protein were evaluated by Western blot. Results ① Compared with the SO group, the serum levels of AMY, ALT, AST, and the hepatocyte AI were significantly increased among the other three groups （P〈0.05）. Compared with the SAP group, the serum levels of AMY, ALT, AST, and the hepatocyte AI were significantly decreased in the LY294002 group and rapamycin group （P〈0.05）. ② Compared with the SO group, the damages of the liver tissues were aggravated among the other three groups.The pathologies of the liver tissues were ameliorated in the LY294002 group and rapamycin group as compared with the SAP group. ③ Compared with the SO group, the levels of p-Akt/Akt, p-mTOR/mTOR were significantly increased among the other three groups （P〈0.05）. Compared with the SAP group, the levels of p-Akt/Akt, p-mTOR/mTOR were significantly decreased in the LY294002 group （P〈0.05）, but in the rapamycin group, only the p-mTOR/mTOR level was significantly decreased （P〈0.05）. Conclusion The activation of PI3IGAkt/mTOR signaling pathway might be one of the reasons for the liver in）ury induced by SAP an

关 键 词：急性坏死性胰腺炎 PI3K/Akt/mTOR信号通路 肝脏损伤 

分 类 号：R576[医药卫生—消化系统]