Study on the effect and mechanism of Dahuang Lingxian formula on regulating intrahepatic bile duct cell inflammation in rats
Objective:To observe the effects of Dahuang Lingxian formula on the expression levels of IKKα,ASK1,MKK3 and CX3CL1 key factors in the MAPK/NF-κB signaling pathway in the intrahepatic cholangiocyte inflammation model of rats,and to explore the ameliorative effects and possible mechanisms of alleviating intrahepatic cholangiocyte inflammation.Methods:45 SD rats were divided into nine groups according to the complete randomization method,with 5 rats in each group:the blank group,the model group,the Dahuang Lingxian Granules group,the NF-κB group,the p38MAPK group,the NF-κB+p38MAPK group,the NF-κB+Dahuang Lingxian Granules group,the p38MAPK+Dahuang Lingxian Granules group,the NF-κB+p38MAPK+Dahuang Lingxian Granules group.Except for the blank group,rats in the remaining groups were injected with 5 mg/kg LPS into the common bile duct to prepare an intrahepatic bile duct inflammation model.After the intragastric admin-istration on the 7th day,the rat bile duct tree was removed,and HE staining was used to observe the degree of inflammation.Western blotting and real-time fluorescence quantitative PCR were used to detect the protein and mRNA expression of IKKα,ASK1,MKK3,and CX3CL1.Results:HE pathology results showed that the inflammation of intrahepatic bile duct tissue and cells in the model group was obvious.After adding Dahuang Lingxian Granules and signal blockers,the inflammation status of in-trahepatic bile ducts was improved compared with before,and the difference in total pathological scores was statistically significant(P＜0.05).Compared with the model group,Dahuang Lingxian granules group,p38MAPK group,NF-κB group,NF-κB+p38MAPK group,NF-κB+Dahuang Lingxiang ranules group,p38MAPK+Dahuang Lingxian granules group,NF-κB+p38MAPK+Dahuang Ling The protein and mRNA expression of ASK1 and CX3CL1 in the Xian Granule group decreased,the expression of MKK3 mRNA increased,and the expression of IKKα in the p38MAPK group and NF-κB+MKK3 protein in the Da-huang Lingxian Granule group increased(P＜0.05).Compared with the Dahuang Lingxian Granules group,The expression of ASK1 and CX3CL1 mRNA decreased in the p38MAPK group,the NF-κB group,the NF-κB+p38MAPK group,the p38MAPK+Dahuang Lingxian Granules group,the NF-κB+Dahuang Lingxian Granules group,the NF-κB+p38MAPK+Da-huang Lingxian Granules group.The expression of MKK3 mRNA in the p38MAPK+Dahuang Lingxian Granules group,NF-κB+Dahuang Lingxian Granules group,and NF-κB+p38MAPK+Dahuang Lingxian Granules group increased(P＜0.05).Compared with the Dahuang Lingxian Granules group,the IKKα protein expression in the p38MAPK group decreased,and the ASK1 and MKK3 protein expressions in the NF-κB+Dahuang Lingxian Granules group increased(P＜0.05),while the NF-κB+p38MAPK+Dahuang Lingxian Granules group increased.The expression of CX3CL1 protein in the granule group decreased(P＞0.05).Conclusion:Dahuang Lingxian Recipe can alleviate the LPS-induced intrahepatic bile duct inflammatory reaction in rats and promote the repair of bile duct cells,thereby achieving the purpose of reducing the occurrence and postoperative recurrence of PIS.Its mechanism of action may be related to inhibiting the NF-κB/MAPK signaling pathway.It is related to the activation of key in-flammatory factors such as IKKα,ASK1,MKK3 and CX3CL1.
国家科技期刊平台
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