Role and mechanism of the high-mobility group box 1/Toll-like receptor 9 signaling pathway in intestinal mucosal barrier injury in severe acute pancreatitis

Objective To investigate the role and mechanism of the high-mobility group box 1 ( HMGB1) /Toll-like receptor 9 ( TLR9) signaling pathway in intestinal mucosal barrier injury in mice with severe acute pancreatitis ( SAP) . Methods A total of KM mice were randomly divided into control group and SAP group. The mice in the SAP group were given intraperitoneal injection of cerulein and lipopolysaccharide to establish a model of SAP, and the samples were collected at 12 hours after modeling. HE staining was used to observe the pathological changes of the pancreas; ELISA was used to measure the serum levels of diamine oxidase ( DAO) and endotoxin core antibody ( EndoCAb) ; TUNEL was used to observe the apoptosis of intestinal mucosal cells; Western Blot was used to measure the changes in the protein expression of HMGB1, TLR9, and nuclear factor-kappa B ( NF-κB) in the small intestine. The t-test was used for comparison of normally distributed continuous data between two groups. Results A mouse model of SAP was successfully established. Compared with the control group, the SAP group had significantly higher serum levels of DAO ( 12. 172 ± 1. 356 vs 4. 341 ± 0. 521, t = 16. 613, P < 0. 001) and EndoCAb ( 32. 480 ± 3. 054 vs 13. 281 ± 2. 105, t = 14. 725, P = 0. 025) . Compared with the control group, the SAP group had a significant increase in apoptotic intestinal mucosal cells ( 19. 54 ± 3. 63 vs 6. 25 ± 2. 1, t = 11. 582, P < 0. 05) . Compared with the control group, the SAP group had significantly higher protein expression of HMGB1 ( 0. 590 ± 0. 004 vs 0. 059 ± 0. 035, t = 47. 336, P = 0. 001) , TLR 9 ( 0. 530 ± 0. 043 vs 0. 070 ± 0. 023, t = 30. 565, P = 0. 034) , and NF-κB ( 0. 670 ± 0. 059 vs 0. 170 ± 0. 032, t = 23. 655, P =0. 014) . Conclusion There is an increase in the expression of HMGB1 in the intestine of SAP mice, which may play an important role in intestinal mucosal barrier injury by activating the downstream TLR9 signaling pathway.