Role of TLR4 in LPS-induced hepatic bile duct injury in rats
YAN Pengzhan
ZHAO Lijin
TU Kui
GU Jin
WANG Fang
Abstract：Objective To investigate the effect and mechanism of Toll-like receptor 4 (TLR4) on hepatic bile duct injury induced by lipopolysaccharide (LPS) in rats.Methods Forty-eight SD rats were randomly divided into four groups.The LPS+siRNA transfection group and the LPS+negative virus group were injected with the siRNA-TLR4 purified adenovirus and the negative control virus, respectively.The control group and the LPS group were injected with the same amount of normal saline.After 24 h, we injected LPS into the common bile ducts of the rats in the LPS group, LPS+siRNA transfection group, and LPS+negative virus group;the control group was injected with the same amount of normal saline.After the molding of 48 and 72 h, we collected the liver tissue samples from 6 rats in each group.HE staining was used to observe the infiltration of inflammatory cells and the morphological changes of bile duct.Immunohistochemical method was used to detect the protein expression of TLR4, cytokeratin 19 (CK19), and Vimentin in hepatic duct epithelial cells, and the mRNA expression of TLR4, CK19, and Vimentin were detected by RT-PCR.Results In the LPS group, inflammatory cell infiltration and interstitial edema of the bile duct were found at 48 h.At 72 h, a large number of inflammatory cells infiltrated around the lumen, accompanied by mild hyperplasia of fibrous connective tissue.In the LPS+siRNA group, only a small number of inflammatory cells were found around the bile duct at 48 h, and the inflammatory cells in the bile duct were slightly increased at 72 h after modeling, but were significantly lower than those in the LPS group.Compared with the control group, the protein and mRNA expression of CK19 in the epithelial cells decreased, and the protein and mRNA expression of TLR4 and Vimentin increased in the other three groups at 48 and 72 h (all P<0.01).The expression of CK19 protein and mRNA in bile duct epithelial cells of the LPS+siRNA transfection group was higher than that of the LPS group and LPS+ negative group, while the protein and mRNA expression of TLR4 and Vimentin was lower than that in the LPS group and LPS+ virus negative group at 48 and 72 h (all P<0.01).Conclusion LPS can promote the occurrence of inflammatory reaction and fibrosis injury of liver and biliary duct tissues and induce TLR4 production, which may lead to the occurrence of EMT and thus increase the degree of liver fibrosis.
Keywords：hepatic bile duct injuryToll-like receptor 4Vimentincytokeratin 19
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 5-8 )