Experimental study of regulating M1/M2 polarization of Kupffer cell by Haoqin Qingdan Decoction to improve intrahepatic bile duct injury in the treatment of primary biliary cholangitis
Objective:Exploring the protective effects and mechanisms of Haoqin Qingdan Decoction on intrahepatic bile ducts in primary biliary cholangitis (PBC)via regulation of Kupffer cell M1/M2 polarization.Methods:60 mice were randomly divided into control group,model group,Haoqinqingdan Decoction (HQQD)high-dose,medium-dose and low-dose groups,ursodeoxycholic acid (UDCA)group,the PBC mouse model induced by 2-octyneic acid and bovine serum albumin (2-OA-BSA)in combination with polyinosine acid (PolyI:C)was subjected to treatment with the corresponding drug for a duration of 12 weeks.The liver histopathological changes were observed by HE staining,the serum γ-GT,TBA,Tbil,AST,ALT were detected by automatic biochemical analyzer,and the expression of iNOS,TNF-α,CD206 and IL-10 mRNA were detected by RT-PCR.The expression of iNOS,TNF-α,CD206 and IL-10 were detected by WB.Results:The pathological results indicated that the hepatic tissue in the control group exhibited a clear portal area structure without any abnormal changes around the interlobular bile ducts.In the model group,multiple inflammatory cell clusters were observed in the portal area,accompanied by granuloma formation and lymphocyte infiltration.Compared to the model group,the number of inflammatory cells in the portal area was reduced in the high-medium-,and low-dose HQQD groups as well as in the UDCA group.The biochemical analysis results showed that,compared to the control group,the serum levels of γ-GT,TBA,TBil,AST,and ALT were elevated to varying degrees in the model group. In contrast,the UDCA group and the high-,medium-,and low-dose HQQD groups exhibited significantly decreased serum levels of γ-GT,TBA,TBil,AST,and ALT compared to the model group.The RT-PCR and Western blot (WB)results demonstrated that,compared to the control group,the hepatic expression levels of iNOS and TNF-αmRNA and proteins were significantly upregulated in the model group,while the expression levels of CD206 and IL-10 mRNA and proteins were significantly downregulated.However,in the UDCA group and the high-,medium-,and low-dose HQQD groups,the expression levels of iNOS and TNF-αmRNA and proteins were markedly downregulated,whereas the expression levels of CD206 and IL-10mRNA and proteins were significantly upregulated compared to the model group.Conclusion:Haoqin Qingdan decoction can reduce M1 polarization and enhance M2 polarization of Kupffer cells in PBC model mice,regulate M1/M2 polarization and improve cholestasis and intrahepatic bile duct injury.
Haoqin Qingdan decoctionprimary biliary cholangitisintrahepatic bile duct injuryKupffer cell polarization
万方数据
维普
