Role of Toll⁃like receptor 4 in the early stage of acetaminophen⁃induced acute liver inj ury in mice
10.19405/j.cnki.issn1000-1492.2023.11.017
- Author:
Xiuliang Zheng
1
;
Mingyue Chen
1
;
Yaqin Qiao
1
;
Haitao Shen
1
;
Yan Lu
1
Author Information
1. Dept of Gastroenterology, The Second Afiliated Hospital of Anhui Medical University,Hefei 230601
- Publication Type:Journal Article
- Keywords:
acetaminophen;
TLR4;
liver injury;
inflammation;
mice;
inbred ICR
- From:
Acta Universitatis Medicinalis Anhui
2023;58(11):1904-1910
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To used Toll⁃like receptor 4( TLR4) inhibitor ( TAK⁃242) investigate the role of TLR4 in the early stage of acetaminophen (APAP) Ⅳinduced acute liver injury in mice.
Methods : Fifty⁃eight male institute of cancer research( ICR) mice were randomly divided into control group ( normal control group , solvent control group , inhibitor control group) and experimental group (APAP 4 ⁃ hour group , APAP + TAK⁃242 4 ⁃ hour group , APAP 12 ⁃ hour group , APAP + TAK⁃242 12 ⁃ hour group) . Mice in the experimental group were given a single dose of APAP (300 mg/kg) and TAK⁃242 (3 mg/kg) were given intraperitoneal injection 3 ⁃ hour before APAP injection. The serum alanine aminotransferase (ALT) level and liver index of mice in each group were compared ;
HE staining showed pathological changes of liver tissue;the level of high mobility group box⁃1 (HMGB1) was determined by immunohistochemistry;the levels of TLR4 , HMGB1 and nuclear factor kappa B(NF⁃κB) protein were detected by Western blot;the levels of monocyte chemoattractant protein⁃1( MCP⁃1) , interleukin( IL) Ⅳ1β , tumor necrosis factor⁃α ( TNF⁃α ) and IL⁃6 genes were determined by real⁃time fluorescence quantitative PCR ( RT⁃qPCR) . The content of IL⁃6 in liver tissue was determined by enzyme linked immunosorbent assay (ELISA) .
Results :HE staining showed liver tissue of mice obvious swelling and congestion of in APAP group at 4 ⁃hour and typical lobular central necrosis in APAP group at 12 ⁃ hour;the degree of liver necrosis in APAP + TAK⁃242 groups at 4 ⁃ hour and 12⁃ hour was less than that in APAP group at the same time point. Compared with the normal control group , serum ALT level , liver index , TLR4 , HMGB1 , NF⁃κB protein content , MCP⁃1 , IL⁃1β , TNF⁃α , IL⁃6 gene levels and IL⁃6 content in liver tissue of APAP 4 ⁃ hour group increased ; serum ALT level , liver index , HMGB1 protein content and IL⁃6 content in liver tissue increased in APAP 12 ⁃ hour group. Compared with APAP 4 ⁃ hour group , serum ALT level , liver index , TLR4 , HMGB1 , NF⁃κB protein content , MCP⁃1 , IL⁃1β , TNF⁃α , IL⁃6 gene level and IL⁃6 content in liver tissue decreased in APAP + TAK⁃242 4 ⁃ hour group. Compared with APAP 12 ⁃hour group , the levels of TLR4 , HMGB1 protein and MCP⁃1 , IL⁃1β , TNF⁃α genes in APAP + TAK⁃242 12 ⁃ hour group decreased.
Conclusion :nhibition of TLR4 may inhibit TLR4/HMGB1 pathway to reduce the inflammatory response in the early stage of acetaminophen⁃induced acute liver injury in mice.
- Full text:2024071117223856414Toll样受体4在对乙酰氨...小鼠急性肝损伤早期中的作用_郑秀良.pdf
