College of Medicine, Southwest Jiaotong University, Chengdu 610031, China.
Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, Chengdu 610083, China.
Exp Biol Med (Maywood). 2021 Sep;246(18):2029-2038. doi: 10.1177/15353702211015144. Epub 2021 May 30.
Abdominal paracentesis drainage (APD), as an effective treatment of severe acute pancreatitis (SAP) in clinical settings, can ameliorate intestinal barrier damage and the overall severity of SAP. However, the mechanism underlying therapeutic effects of APD on damaged intestinal mucosal barrier during SAP is still unclear. Here, SAP was induced by injecting 5% Na-taurocholate retrograde into the biliopancreatic duct of rats to confirm the benefits of APD on enteral injury of SAP and further explore the possible mechanism. Abdominal catheter was placed after SAP was induced in APD group. As control group, the sham group received no operation except abdominal opening and closure. By comparing changes among control group, sham group, and APD group, APD treatment obviously lowered the intestinal damage and reduced the permeation of intestinal mucosal barrier, which was evidenced by intestinal H&E staining, enteral expression of tight junction proteins, intestinal apoptosis measurement and detection of serum diamine oxidase, intestinal fatty acid binding protein and D-lactic acid. Furthermore, we found that APD polarized intestinal macrophages toward M2 phenotype by the determination of immunofluorescence and western blotting, and this accounts for the benefits of APD for intestinal injury in SAP. Importantly, the protective effect against intestinal injury by APD treatment was mediated through the inhibited ASK1/JNK pathway. In summary, APD improved the intestinal mucosal barrier damage in rats with SAP through an increasing portion of M2 phenotype macrophages in intestine via inhibiting ASK1/JNK pathway.
腹腔穿刺引流 (APD) 作为临床治疗重症急性胰腺炎 (SAP) 的有效方法，可改善肠道屏障损伤和 SAP 的整体严重程度。然而，APD 治疗 SAP 时对受损肠道黏膜屏障的治疗效果的机制尚不清楚。在这里，通过向大鼠的胆胰管逆行注射 5%牛磺胆酸钠来诱导 SAP，以确认 APD 对 SAP 肠内损伤的益处，并进一步探讨可能的机制。在 APD 组诱导 SAP 后放置腹部导管。作为对照组，假手术组仅进行腹部切开和关闭，而不进行任何操作。通过比较对照组、假手术组和 APD 组之间的变化，APD 治疗明显降低了肠道损伤，减少了肠道黏膜屏障的通透性，这可以通过肠道 H&E 染色、肠紧密连接蛋白的肠内表达、肠道细胞凋亡测定以及血清二胺氧化酶、肠脂肪酸结合蛋白和 D-乳酸的检测来证实。此外，我们通过免疫荧光和 Western blot 检测发现，APD 将肠道巨噬细胞极化为 M2 表型，这是 APD 对 SAP 肠损伤有益的原因。重要的是，APD 通过抑制 ASK1/JNK 通路介导对肠道损伤的保护作用。综上所述，APD 通过抑制 ASK1/JNK 通路增加肠道中 M2 表型巨噬细胞的比例，改善 SAP 大鼠的肠道黏膜屏障损伤。
