Study On Clinical Efficacy And Mechanism Exploration Of Huoxue Ruanjian Fuzheng Fang In Intervention Of Liver Fibrosis After Hepatitis B

Objective:The network pharmacology method was used to investigate the targets of HXRJFZ treating hepatitis B liver fibrosis and to screen the possible signaling pathway.The clinical research use HXRJFZ to treat liver fibrosis patients with blood stasis and qi deficiency.This study observes the effectiveness and safety of this treatment.It measures tissue inhibitor metalloproteinase-1 and transforming growth factor-β1 in serum,from which to explore the effective mechanism providing scientific basis for clinical application.Methods:1.Network pharmacology research:TCMSP,TCMID,SwissTargetPrediction,PubChem,DisGeNET,OMIM and GeneCards databases were used to screen the active components of HXRJFZ and the related target genes of hepatitis B liver fibrosis,and the network diagram of"drug-component-target-disease" was constructed with the software of Cytoscape.The protein interaction network was constructed by string database,and the key target of HXRJFZ in the treatment of hepatitis B liver fibrosis was analyzed by Metascape for GO enrichment analysis and KEGG enrichment analysis to obtain the mechanism of HXRJFZ in the treatment of hepatitis B liver fibrosis.2.Clinical research:The 63 hepatitis B liver fibrosis patients with blood stasis and qi deficiency who met the criteria,were divided into Chinese medicine group and control group by using random number method.Chinese medicine group has 33 cases,but 3 patients is off.Control group has 30 cases.Besides the basic antiviral therapy,the Chinese medicine group patients were treated with HXRJFZ,the other group were given Fu Fang Bie Jia Ruan Gan tablets.Two groups have same time to take the medicine for six months.Before and after treatment it need to record symptom integral scores,detect the liver stiffness measurements,examine liver function,proteins,coagulation function,hepatic fibrosis indexes,transforming growth factor-β1 and tissue inhibitor metalloproteinase-1 in serum,and calculate the noninvasive liver fibrosis indexes(APRI、FIB-4).It also need to observe related safety index changes before the treatment and after three months and after all treatment.Then compare all the index and make statistical analysis.Results:Results of network pharmacology experiment33 active components of HXRJFZ were screened,involving 103 targets.HXRJFZ in the treatment of hepatitis B liver fibrosis mainly involves the biological process,cellular component,molecular function and other multilevel biological functions,through the PI3K-Akt signaling way,mTOR signaling way,phospholipase D signaling way,HIF-la signaling way,FoxO signaling way,JAK-STAT signaling way,IL-17 signaling way,MAPK signaling way,AMPK signaling way,TNF signaling way,PPARγ signaling way,and other signaling pathways to play the role of anti-fibrosis.Results of the Clinical research(1)Imaging indicator of liver fibrosis:compared with pretreatment,both Chinese medicine group and control group can obviously reduce the liver stiffness measurements(P<0.01),compared with control group,effect of the Chinese medicine group is better(P<0.05).(2)Serum markers of liver fibrosis:compared with pretreatment,Chinese medicine group can obviously reduce CIV level in the serum(P<0.01),but no obvious effect was found in the control group after treatment.(3)Noninvasive liver fibrosis indexes:compared with pretreatment,both Chinese medicine group and control group can obviously reduce the level of FIB-4(P<0.05),compared with control group,effect of the Chinese medicine group is better(P<0.05);compared with pretreatment,Chinese medicine group can obviously reduce the level of APRI(P<0.01),but no obvious effect was found in the control group.(4)Liver function:compared with pretreatment,both Chinese medicine group and control group can reduce the TBIL level in the serum(P<0.05),and no obvious difference was found between the two control groups;compared with pretreatment,Chinese medicine group can obviously reduce the AST level in the serum(P<0.01),but no obvious effect was found in the control group.(5)Serum proteins:compared with pretreatment,both Chinese medicine group and control group can’t find obvious.(6)Coagulation function:compared with pretreatment,Chinese medicine group can obviously reduce the level of PTA and PLT(P<0.01),but no same obvious effect was found in the control group.(7)TIMP-1 and TGF-β1:compared with pretreatment,Chinese medicine group can reduce the level of TIMP-1 in the serum(P>0.05),control group can reduce the level of TGF-β1 in the serum(P>0.05),but neither between groups nor between pretreatment and aftertreatment can obvious effect be found.(8)syndromes scores:compared with pretreatment,both Chinese medicine group and control group can obviously improve the syndromes scores(P<0.01),compared with control group,effect of the Chinese medicine group is better(P<0.01).Conclusion:1.The network pharmacology study suggests that HXRJFZ has the characteristics of multi-level,multi-system and overall intervention in treating hepatitis B liver fibrosis.2.According to the comparison of imaging indicator,serum fibrosis markers and noninvasive liver fibrosis index,HXRJFZ can significantly inhibit the formation of hepatic fibrosis3.HXRJFZ can significantly improve syndrome,alleviate hepatitis and regulate coagulation function.4.There is no significant reduction in tissue inhibitor metalloproteinase 1(TIMP-1)and transforming growth factor-β1(TGF-β1),HXRJFZF may have some inhibition to the two factors,but whether they are the main interference factors still needs further research.