Effects of Lycium barbarum polysaccharides on ANIT-induced cholestatic liver injury and the expression of TLR4/MyD88/NF-κB pathway-related proteins in rats
Objective To observe the effects of Lycium barbarum polysaccharides(LBP)on α-naphthyl isothiocyanate induced cholestatic liver injury and the expression of Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa-B(TLR4/MyD88/NF-κB)pathway-related proteins.Methods The normal control group,the model group,the LBP low-,middle-and high-dose groups and the positive control group were established.After 6 weeks of continuous intragastric administration of test substances,rats'blood and liver tissue samples were collected to detect serum biomarker indicators,total white blood cell(WBC)count and classification indicators,inflammatory factor content in liver tissue,and relative expression levels of TLR4,NF-κB,phospho-nuclear factor kappa B(pNF-κB)and MyD88 proteins.HE staining and Masson staining methods were used to observe the morphological changes in the liver tissue of rats,and histopathological scoring was performed.Results Compared with the normal control group,the serum levels of y-glutamyltransferase(γ-GGT),alkaline phosphatas(ALP),total bile acid(TBA),total bilirubin(TBIL),cholesterol(CHOL),alanine aminotransferase(ALT)and aspertate aminotransferase(AST)as well as total WBC count,lymphocyte(LYMPH),neutrophil(NEUT)and monocyte(MONO)in the model group increased(all P＜0.01),the levels of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),interleukin-6(IL-6),monocyte chemotactic protein-1(CCL2)and macrophage inflammatory protein-2(CXCL2)increased,the expression levels of TLR4,pNF-κB and MyD88 were upregulated(P＜0.01),liver weight and liver to body weight ratio increased,pathological changes in the liver such as infiltration of inflammatory cells,bile duct hyperplasia and fibrous tissue hyperplasia were observed,and the histological observation score increased(P＜0.01).Compared with the model group,the serum γ-GGT,TBA,TBIL and ALT levels,WBC count,LYMPH and NEUT in the LBP high-dose group decreased(P＜0.05 or P＜0.01),the levels of TNF-α,IL-1,IL-6 and CXCL2 in the liver tissue decreased,the relative expression levels of TLR4,pNF-κB and MyD88 proteins were down-regulated(P＜0.05 or P＜0.01),liver to body weight ratio decreased by 12％,infiltration of inflammatory cells,bile duct hyperplasia and fibrous tissue hyperplasia were alleviated,and the histopathological observation score decreased(P＜0.01).Conclusion LBP at the dose level of 540 mg/kg has a relieving effect on cholestatic liver injury in rats,which may be related to down-regulating the expression of TLR4/MyD88/NF-κB pathway-related proteins and inhibiting excessive inflammatory response in the liver.
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