期刊
EXPERIMENTAL BIOLOGY AND MEDICINE
卷 246, 期 18, 页码 2029-2038出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/15353702211015144
关键词
Severe acute pancreatitis; abdominal paracentesis drainage; macrophage polarization; intestinal mucosal barrier; apoptosis; ASK1; JNK pathway
资金
- National Natural Science Foundation of China [81772001]
- National Clinical Key Subject of China [41732113]
- Technology Plan Program of Sichuan Provence [2015SZ0229, 2018JY0041, 2019YJ0277]
The study demonstrated that abdominal paracentesis drainage (APD) can improve intestinal mucosal barrier damage caused by severe acute pancreatitis (SAP) by modulating the phenotype of intestinal macrophages, and this protective effect is mediated through inhibition of the ASK1/JNK pathway.
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.
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