| Objective: Through clinical observation,it can be confirmed that "tonifying kidney and generating liver"(Jiawei Jisheng Shenqi Decoction)can effectively treat patients with hepatitis B cirrhosis,and can promote the secretion of erythropoietin(EPO);Through animal experiments,it can be confirmed that "tonifying kidney and generating liver"(Fuwei Jisheng Shenqi Decoction)can promote the homing of bone marrow mesenchymal stem cells to the liver by promoting EPO secretion,and its mechanism of action is preliminary discussed.Methods: Clinical observation: 84 patients with hepatitis B cirrhosis with spleen-kidney Yang deficiency syndrome were randomly divided into control group and treatment group according to random number table method,42 cases in each group.The control group was treated with Entecavir dispersible tablets or Entecavir capsules,0.5mg/time,once/day;The treatmen group was additively treated with Jiawei Jisheng Shenqi Decoction on the basis of the control group.The treatment course of patients in both groups was 6 months,and the relevant indicators were tested every 3 months.After the end of the course of treatment,clinical symptom score,clinical efficacy of traditional Chinese medicine,liver function(ALT,AST,ALB),serum EPO level,serum HBV-DNA negative conversion rate,liver hardness value,liver B-ultrasound score,safety and adverse reactions of two groups were observed before and after treatment.Animal experiments: Adaptability will only 58 SPF SD health rats fed 7 days,from random separated executed after the 4 rats bone marrow mesenchymal stem cells for cell culture,between random separated eight healthy rats as blank group,the rest of the liver cirrhosis in rats to build mode,copy the liver cirrhosis in rats induced by eight w model,8 weeks were executed,randomly selected 4 rats Histopathological sections of liver were taken to prove the success of liver cirrhosis modeling.Two mice died during the modeling process.Forty cirrhosis rats successfully established were randomly divided into 6 groups,8 rats in each group,model group,Jiawei Jisheng Shenqi Decoction group alone,BMSCs transplantation group alone,BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation +EPOR antagonist + Jiawei Jisheng Shenqi Decoction group plus blank group.The model group was not given any intervention.The blank group was given drinking water by gavage.Jiawei Jisheng Shenqi Decoction group was given Jiawei Jisheng Shenqi Decoction by gastric gavage;BMSCs transplantation group was given caudal vein BMSCs transplantation;BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group was given by gavage of tail vein BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group;BMSCs transplantation + EPOR antagonist + Jiawei Jisheng Shenqi Decoction group was treated with BMSCs transplantation through tail vein,injection of EPOR antagonist injection through tail vein,and gavage of Jiawei Jisheng Shenqi Decoction.Jiawei Jisheng Shenqi Decoction and drinking water were given orally once a day,8.75g/kg/d.BMSCs transplantation was given once a week,from the beginning of the 9th week for 4 weeks to the end of the 12 th week.After the intervention,the general condition of the rats was observed.After 12 W,the rats were fasted for 12 h,and then the abdominal aorta blood was collected and liver tissue was obtained.Hepatic histopathological status was observed by HE staining;Liver function(ALT,AST,ALB)was detected by automatic biochemical detector;The levels of EPO and hepatocyte growth factor(HGF)in peripheral blood of rats were determined by ELISA;The protein expressions of EPOR,c-Met,SDF-1 and CXCR4 in liver tissues of rats in each group were detected by Western blot.Results: Clinical observation: After treatment,clinical symptom score,clinical efficacy of traditional Chinese medicine,liver function(ALT,AST,ALB),serum EPO level,serum HBV-DNA negative conversion rate,liver hardness value,liver B-ultrasound score in treatment group were significantly improved compared with before treatment;In the control group,clinical symptom score,clinical efficacy of traditional Chinese medicine,serum HBV-DNA negative conversion rate,liver function(ALT,AST),liver color Doppler score were improved compared with before treatment,while EPO and ALB levels in the control group were not significantly changed.There were significant differences in clinical symptom scores and TCM clinical efficacy between treatment group and control group after 6 months(P<0.01);ALT and AST levels in treatment group and control group were significantly different after 3 months of treatment(P<0.01),but there was no significant difference after 6 months of treatment(P>0.05);There were significant differences in ALB levels between treatment group and control group after 3 and 6 months of treatment(P<0.01);There were significant differences in EPO levels between treatment group and control group after 3 months and 6 months of treatment respectively(P<0.01);There was no significant difference in serum HBV-DNA conversion rate between the treatment group and the control group after 3 months and 6 months of treatment respectively(P>0.05);There were significant differences in liver hardness values between treatment group and control group after 3 and 6 months of treatment respectively(P<0.01);There was significant difference between the treatment group and the control group in the improvement rate of liver B ultrasonography score after 6 months of treatment(P<0.01).There were no toxic and side effects and adverse reactions in the two groups during the treatment.Animal experiments: General situation of rats: After intervention treatment,the general condition of rats in the Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation alone group,BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation +EPOR antagonist + Jiawei Jisheng Shenqi Decoction group was improved compared with the model group,and the condition of rats in the BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group was the best.Hepatic histopathology indicated that the liver histopathology of the model group rats was as follows: false lobule formation and disordered structure,disordered arrangement of liver cells,severe fibrous tissue hyperplasia,necrosis of liver cells,and inflammatory cell invasion.After different interventions,compared with the model group,the liver lobule structure,fibrosis,liver cell necrosis and inflammatory cells in each intervention group were improved to varying degrees,among which BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group showed the best improvement.Comparison of liver function(ALT,AST,ALB)in each group: compared with blank group,ALT,AST water content in model group was increased while ALB level was decreased,the difference was statistically significant(P<0.01);Compared with model group,ALT and AST of liver function of rats in Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation group alone,BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation +EPOR antagonist +Jiawei Jisheng Shenqi Decoction group decreased to different degrees,while ALB increased to different degrees,the difference was statistically significant(P<0.01).The ALT and AST decreased and ALB increased in the group of BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction,and the difference was statistically significant compared with the group of Jiawei Jisheng Shenqi Decoction,BMSCs transplantation group,and BMSCs transplantation +EPOR antagonist + Jiawei Jisheng Shenqi Decoction(P<0.01).Serum EPO and HGF levels: Compared with blank group,the levels of EPO and HGF in model group decreased,with statistical significance(P<0.01).Compared with model group,the levels of EPO and HGF of rats in Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group,and BMSCs transplantation+EPOR antagonist + Jiawei Jisheng Shenqi Decoction group were all increased,the differences were statistically significant(P<0.01),while the levels of EPO and HGF in BMSCs transplantation alone group were slightly increased.There was no statistical significance in the difference(P>0.05),and the increase of EPO and HGF was the most significant in the BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group.Expression of EPOR,c-Met,SDF-1 and CXCR4 proteins in liver tissue:Compared with model group,the protein levels of EPOR,C-MET,SDF-1 and CXCR4 in liver tissue of Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation group alone,BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation +EPOR antagonist +Jiawei Jisheng Shenqi Decoction group were all changed.The difference was statistically significant(P<0.01),and the protein levels of EPOR,C-MET,SDF-1 and CXCR4 in BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction group increased most obviously,compared with Jiawei Jisheng Shenqi Decoction group,BMSCs transplantation alone group,BMSCs transplantation +EPOR antagonist + Jiawei Jisheng Shenqi Decoction group,The difference was statistically significant(P<0.01).Conclusion: Clinical observation shows that Enticavir dispersive tablet or(Enticavir capsule)combined with Jisheng Shenqi Decoction in the treatment of hepatitis B cirrhosis patients with spleen-kidney Yang deficiency syndrome can significantly reduce clinical symptom score,improve clinical efficacy of traditional Chinese medicine,improve liver function(ALT,AST,ALB),increase serum EPO level,and promote HBV-DNA negative conversion.It is safe and reliable to reduce liver hardness value and B ultrasound score without adverse reaction.Animal experiments show that BMSCs transplantation combined with Jiawei Jisheng Shenqi Decoction can effectively treat cirrhosis,which may be related to the activation of SDF-1/CXCR4 axis through EPO/EPOR-HGF/ C-Met pathway,providing a certain basis for future studies on the application of traditional Chinese medicine combined with BMSCs transplantation in the treatment of cirrhosis. |
PDF Full Text Request