Department of the First General Surgery, Qingdao Municipal Hospital, Dalian Medical University, No. 1 Jiaozhou Road, Qingdao, 266011, Shandong, China.
Department of the First General Surgery, Qingdao Municipal Hospital, Dalian Medical University, No. 1 Jiaozhou Road, Qingdao, 266011, Shandong, China.
Exp Cell Res. 2023 Jul 15;428(2):113630. doi: 10.1016/j.yexcr.2023.113630. Epub 2023 May 17.
Patients with severe acute pancreatitis (SAP) have a compromised intestinal barrier with decreased barrier function and increased cell death. Intestinal epithelial cells (IECs) create a physicochemical barrier that anchors bacteria in the intestine. Recent studies have shown that the stimulator of interferons genes (STING) signaling pathway plays an important function in a number of inflammatory conditions.
The rat SAP model was established by retrograde injection of freshly prepared sodium taurocholate into the biliopancreatic duct. Serum amylase (AMY), lipase (LIPA), interleukin (IL)-6, interferon (IFN)-β, tumor necrosis factor (TNF)-α, intestinal-type fatty acid binding protein (FABP2), diamine oxidase (DAO) and endotoxin (ET) levels were measured in rats. H&E staining was used to assess histological changes in the intestine and pancreas. The expression of intestinal epithelial cell tight junction (TJ) proteins and STING signaling pathway proteins and genes were measured by RT- PCR, Western blot and immunofluorescence staining were used to analyze. The expression of STING signaling pathway proteins in pancreas were measured by Western blot were used to analyze. TUNEL was used to detect IECs death.
Upregulation of STING pathway-related proteins and genes occurred after sap-induced IECs. In addition, C-176 reduced serum AMY, LIPA, TNF-α, IL-6, INF-β, FABP2, DAO and endotoxin levels and decreased pancreatic and intestinal histopathological injury in SAP rats; DMXAA aggravated serum AMY, LIPA, TNF-α, IL-6, INF-β, FABP2, DAO and endotoxin levels and increased pancreatic and intestinal histopathological injury in SAP rats.
The results suggest that inhibition of STING signaling can alleviate IECs after SAP, and activation of STING signaling can aggravate IECs after SAP.
重症急性胰腺炎（SAP）患者的肠道屏障受损，屏障功能降低，细胞死亡增加。肠上皮细胞（IECs）形成物理化学屏障，将细菌固定在肠道内。最近的研究表明，干扰素基因刺激物（STING）信号通路在许多炎症条件中发挥着重要作用。
通过向胆胰管逆行注射新鲜制备的牛磺胆酸钠建立大鼠 SAP 模型。测定大鼠血清淀粉酶（AMY）、脂肪酶（LIPA）、白细胞介素（IL）-6、干扰素（IFN）-β、肿瘤坏死因子（TNF）-α、肠型脂肪酸结合蛋白（FABP2）、二胺氧化酶（DAO）和内毒素（ET）水平。H&E 染色评估肠和胰腺的组织学变化。通过 RT-PCR 测定肠道上皮细胞紧密连接（TJ）蛋白和 STING 信号通路蛋白和基因的表达，通过 Western blot 和免疫荧光染色分析。Western blot 测定胰腺中 STING 信号通路蛋白的表达。TUNEL 检测 IEC 死亡。
SAP 诱导 IECs 后，STING 通路相关蛋白和基因上调。此外，C-176 降低 SAP 大鼠血清 AMY、LIPA、TNF-α、IL-6、INF-β、FABP2、DAO 和内毒素水平，减轻胰腺和肠道组织病理学损伤；DMXAA 加重 SAP 大鼠血清 AMY、LIPA、TNF-α、IL-6、INF-β、FABP2、DAO 和内毒素水平，增加胰腺和肠道组织病理学损伤。
抑制 STING 信号可减轻 SAP 后 IECs 的损伤，激活 STING 信号可加重 SAP 后 IECs 的损伤。
