Xu Ping, Wang Jing, Yang Zhi-wen, Lou Xiao-li, Chen Cheng
Department of Gastroenterology, Songjiang Hospital Affiliated the First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
PLoS One. 2013 Nov 28;8(11):e81767. doi: 10.1371/journal.pone.0081767. eCollection 2013.
The phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) pathway plays a key role in inflammation. However, the regulatory roles of PI3K/Akt in severe acute pancreatitis (SAP) have not been elucidated. The aim of this study was to investigate the impact of wortmannin, a PI3K/Akt inhibitor, on SAP rats through exposure to sodium taurocholate (STC) after 3 h and 6 h. The SAP group was found to have a significant increase in pancreas Akt expression, along with the activation of serum amylase, TNF-α, IL-1β, and IL-6, and pancreas histological aggravation. The administration of wortmannin in SAP rats reduced Akt expression, attenuated the level of serum amylase and inflammation factor, and alleviated the damage of pancreatic tissue. Furthermore, the administration of wortmannin led to an obvious reduction in NF-κB and p38MAPK expression in SAP rats. These findings showed that the PI3K/Akt inhibitor wortmannin decreases inflammatory cytokines in SAP rats and suggests its regulatory mechanisms may occur through the suppression on NF-κB and p38MAPK activity.
磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路在炎症中起关键作用。然而,PI3K/Akt在重症急性胰腺炎(SAP)中的调控作用尚未阐明。本研究旨在通过在3小时和6小时后暴露于牛磺胆酸钠(STC),研究PI3K/Akt抑制剂渥曼青霉素对SAP大鼠的影响。结果发现,SAP组胰腺Akt表达显著增加,同时血清淀粉酶、TNF-α、IL-1β和IL-6激活,胰腺组织学加重。给SAP大鼠注射渥曼青霉素可降低Akt表达,减轻血清淀粉酶和炎症因子水平,减轻胰腺组织损伤。此外,注射渥曼青霉素可使SAP大鼠的NF-κB和p38MAPK表达明显降低。这些结果表明,PI3K/Akt抑制剂渥曼青霉素可降低SAP大鼠的炎性细胞因子水平,提示其调节机制可能通过抑制NF-κB和p38MAPK活性而发生。