激活PI3K/AKT/mTOR通路降低急性胰腺炎模型大鼠炎性反应  

Activation of PI3K/AKT/mTOR pathway can alleviate inflammation in acute pancreatitis of rat model

作　　者：韩崇屹 王久吉 朱丽美 刘前 孙建利[1] HAN Chongyi;WANG Jiuji;ZHU Limei;LIU Qian;SUN Jianli(Department of Emergency,Chengde Central Hospital(Second Affiliated Hospital of Chengde Medical College),Chengde 067000,China)

机构地区：[1]承德市中心医院(承德医学院第二附属医院)急诊科,河北承德067000

出　　处：《基础医学与临床》2024年第11期1563-1568,共6页Basic and Clinical Medicine

摘　　要：目的探讨激活PI3K/AKT/mTOR通路是否可降低急性胰腺炎(AP)模型大鼠炎性反应。方法将SD大鼠分为sham组、model组、谷氨酰胺(Gln)组、Gln+LY294002(PI3K/AKT/mTOR通路抑制剂)组;检测腹内压(IAP)和腹水量(AS);检测血清淀粉酶(AMY)、二胺氧化酶(DAO)、白细胞介素(IL-1β、IL-6)、肿瘤坏死因子(TNF-α)水平。观察胰腺、小肠组织形态;检测各组大鼠回肠组织中PI3K、Akt、mTOR基因表达和胞质紧密连接蛋白(ZO-1)、紧密连接蛋白(occludin-1)、PI3K、Akt、mTOR蛋白表达水平。结果与sham组相比,model组大鼠IAP和AS、IL-1β、IL-6、TNF-α水平、AMY、DAO水平、胰腺和小肠组织病理损伤评分显著升高,大鼠回肠组织中PI3K mRNA、Akt mRNA、mTOR mRNA表达水平、ZO-1、occludin-1、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR表达水平显著降低(P<0.05);与model组相比,Gln组IAP和AS、IL-1β、IL-6、TNF-α水平、AMY、DAO水平、胰腺和小肠组织病理损伤评分显著降低,大鼠回肠组织中PI3K mRNA、Akt mRNA、mTOR mRNA表达、ZO-1、occludin-1、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR表达水平显著升高(P<0.05);LY294002可部分逆转Gln对AP大鼠的治疗作用。结论激活PI3K/AKT/mTOR通路可降低AP大鼠炎性反应,改善其肠胃功能。Objective To investigate whether activation of PI3K/AKT/mTOR pathway can reduce inflammation in acute pancreatitis(AP)rats.Methods SD rats were grouped into sham surgery group,model group,Gln group,and Gln+LY294002 group(PI3K/AKT/mTOR pathway inhibitors).Intra-abdominal pressure(IAP),ascites volume(AS),serum amylase(AMY),diamine oxidase(DAO),interleukin(IL-1β,IL-6),Tumor necrosis factor(TNF-α)were measured.The pathological change in pancreatic and small intestinal tissues was evaluated by microscopy;The expression of PI3K,Akt and mTOR genes and cytoplasm compact linking protein(ZO-1),compact linking protein(occludin-1),PI3K,Akt and mTOR in ileum of each group were detected.Results Compared with the sham surgery group,the IAP and AS,IL-1β,IL-6,TNF-α,AMY,DAO,and pathological injury scores of pancreas and small intestine in the model group were obviously increased;The expression of PI3K mRNA,Akt mRNA,mTOR mRNA,ZO-1,occludin-1,p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in rat ileum tissue significantly reduced(P<0.05).Compared with the model group,the level of IAP and AS,IL-1β,IL-6,TNF-α,AMY,DAO and pathological injury scores of pancreas and small intestine in the Gln group were significantly reduced;The expression of PI3K mRNA,Akt mRNA,mTOR mRNA,ZO-1,occludin-1,p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in rat ileum tissue was significantly increased(P<0.05);LY294002 could specifically reverse the therapeutic effect of Gln on acute pancreatitis in rats.Conclusions Activation of PI3K/AKT/mTOR pathway may reduce inflammation and improve gastrointestinal function in rats with acute pancreatitis.

关 键 词：PI3K/AKT/mTOR通路 急性胰腺炎 胃肠功能障碍 

分 类 号：R576[医药卫生—消化系统] R574[医药卫生—内科学]