The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis
Abstract Objective To investigate the effect of the TLR4/MyD88/NF-κB (Toll-like receptor 4/myeloid differentiation factor/nuclear factor kappa B) signalling pathway on the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis. Methods A mouse model of sepsis was esta...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | BMC Anesthesiology |
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| Online Access: | https://doi.org/10.1186/s12871-023-02374-9 |
| _version_ | 1797388140364693504 |
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| author | Song Wenying Huang Jing Li Ying Ding Hui |
| author_facet | Song Wenying Huang Jing Li Ying Ding Hui |
| author_sort | Song Wenying |
| collection | DOAJ |
| description | Abstract Objective To investigate the effect of the TLR4/MyD88/NF-κB (Toll-like receptor 4/myeloid differentiation factor/nuclear factor kappa B) signalling pathway on the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis. Methods A mouse model of sepsis was established by classical caecal ligation and perforation. Forty-four SPF C57BL/6 mice were randomly divided into the following four groups with 11 mice in each group: the control group (Con group), ulinastatin group (Uti group), Uti + LPS (lipopolysaccharide, LPS) group (Uti + LPS group) and LPS group. Mice in the Con group and Uti group received saline or ulinastatin injected 2 h after modelling; Mice in the Uti + LPS group received LPS injected 0 h after modelling, other procedures were the same as in the Uti group; Mice in the LPS group received LPS only. At 48 h after surgery, the levels of TNF-α (tumour necrosis factor-α, TNF-α), IL-6 (interleukin-6, IL-6) and IL-1β (interleukin-1β, IL-1β) in vein, and the expression of TLR4, MyD88 and NF-κB mRNA in small intestinal mucosa tissues using ELISA and RT‒PCR. Results The pathological specimens showed increased inflammatory injury in the Con and LPS groups, while these injuries and changes improved in the Uti group. The scores of intestinal mucosal injury at 48 h of Uti injection were significantly lower than those of the Con group (P < 0.001), while the scores of intestinal mucosal injury of Uti + LPS were significantly higher than those of the Uti group (P = 0.044). The expression of TNF-α, IL-6 and IL-1β in the Uti decreased significantly at 48 h after surgery than that in the Con group (P = 0.001, P = 0.014, P = 0.004), while the expression of TNF-α, IL-6 and IL-1β in the Uti + LPS group increased significantly after surgery than that in the Uti group (P = 0.026, P = 0.040, P = 0.039). The expression of TLR4, MyD88 and NF-κB mRNA in the Uti group decreased significantly compared with that in the Con group (P = 0.001, P = 0.021, P = 0.007), while the expression of TLR4, MyD88 and NF-κB mRNA in the Uti + LPS group was higher than that in the Uti group (P = 0.023, P = 0.040, P = 0.045). Conclusion These findings indicate that the protective effect of ulinastatin on the intestinal mucosal barrier against sepsis may be mediated through the TLR4/MyD88/NF-κB pathway. |
| first_indexed | 2024-03-08T22:35:27Z |
| format | Article |
| id | doaj.art-8761840128844073ac3686250afe0dad |
| institution | Directory Open Access Journal |
| issn | 1471-2253 |
| language | English |
| last_indexed | 2024-03-08T22:35:27Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Anesthesiology |
| spelling | doaj.art-8761840128844073ac3686250afe0dad2023-12-17T12:28:08ZengBMCBMC Anesthesiology1471-22532023-12-012311710.1186/s12871-023-02374-9The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsisSong Wenying0Huang Jing1Li Ying2Ding Hui3Department of Anesthesiology, Shaanxi Provincial Hospital, The Third Affiliated Hospital of Xi’an JiaoTong UniversityXi’an Medical UniversityXi’an Medical UniversityDepartment of Anesthesiology, Shaanxi Provincial Hospital, The Third Affiliated Hospital of Xi’an JiaoTong UniversityAbstract Objective To investigate the effect of the TLR4/MyD88/NF-κB (Toll-like receptor 4/myeloid differentiation factor/nuclear factor kappa B) signalling pathway on the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis. Methods A mouse model of sepsis was established by classical caecal ligation and perforation. Forty-four SPF C57BL/6 mice were randomly divided into the following four groups with 11 mice in each group: the control group (Con group), ulinastatin group (Uti group), Uti + LPS (lipopolysaccharide, LPS) group (Uti + LPS group) and LPS group. Mice in the Con group and Uti group received saline or ulinastatin injected 2 h after modelling; Mice in the Uti + LPS group received LPS injected 0 h after modelling, other procedures were the same as in the Uti group; Mice in the LPS group received LPS only. At 48 h after surgery, the levels of TNF-α (tumour necrosis factor-α, TNF-α), IL-6 (interleukin-6, IL-6) and IL-1β (interleukin-1β, IL-1β) in vein, and the expression of TLR4, MyD88 and NF-κB mRNA in small intestinal mucosa tissues using ELISA and RT‒PCR. Results The pathological specimens showed increased inflammatory injury in the Con and LPS groups, while these injuries and changes improved in the Uti group. The scores of intestinal mucosal injury at 48 h of Uti injection were significantly lower than those of the Con group (P < 0.001), while the scores of intestinal mucosal injury of Uti + LPS were significantly higher than those of the Uti group (P = 0.044). The expression of TNF-α, IL-6 and IL-1β in the Uti decreased significantly at 48 h after surgery than that in the Con group (P = 0.001, P = 0.014, P = 0.004), while the expression of TNF-α, IL-6 and IL-1β in the Uti + LPS group increased significantly after surgery than that in the Uti group (P = 0.026, P = 0.040, P = 0.039). The expression of TLR4, MyD88 and NF-κB mRNA in the Uti group decreased significantly compared with that in the Con group (P = 0.001, P = 0.021, P = 0.007), while the expression of TLR4, MyD88 and NF-κB mRNA in the Uti + LPS group was higher than that in the Uti group (P = 0.023, P = 0.040, P = 0.045). Conclusion These findings indicate that the protective effect of ulinastatin on the intestinal mucosal barrier against sepsis may be mediated through the TLR4/MyD88/NF-κB pathway.https://doi.org/10.1186/s12871-023-02374-9SepsisUlinastatinTLR4 |
| spellingShingle | Song Wenying Huang Jing Li Ying Ding Hui The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis BMC Anesthesiology Sepsis Ulinastatin TLR4 |
| title | The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis |
| title_full | The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis |
| title_fullStr | The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis |
| title_full_unstemmed | The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis |
| title_short | The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis |
| title_sort | role of tlr4 myd88 nf κb in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis |
| topic | Sepsis Ulinastatin TLR4 |
| url | https://doi.org/10.1186/s12871-023-02374-9 |
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