Study On The Prescription And Medication Rule Of The Method Of Invigorating The Spleen And Replenishing Qi In The Treatment Of Liver Cancer And Its Influence On The Tumor Microenvironment

Objective:Through the systematic analysis of th e prescription and medication rules of the spleen-invigorating and qi-invigorating method for treating liver cancer,the syndrome differentiation and treatment system of the spleen-invigorating and qi-invigorating meth od for treating liver cancer is further improved,which is helpful for guiding clinical medication.From the perspective of liver cancer microenvironment to discuss the therapeutic mechanism of invigorating spleen and qi method for liver cancer,and the mechanism of intervention of spleen and qi method on the occurrence and development of liver cancer by regulating tumor microenvironment is preliminarily explained.Methods:1.Research on th e usage of drugs:Taking CNKI databases,Wanfang databases and Vip databases as data sources,medical literatures published in China in the past 30 years,including the treatment of PLC with traditional Chinese medicine,were retrieved and read one by one.519 literatures with medical records were selected.Among them,there are 107 documents that meet the inclusion criteria,and 124 complete prescriptions are collected.Then through the traditional Chinese medicine inheritance auxiliary platform(V2.5)to carry on the statistics and the analysis to the prescription.then summarizes the prescription medication rule which mainly treats liver cancer with the spleen invigorating and qi invigorating method.2.Animal experiment:Seventy five SD rats were randomly divided into normal group(n=15),model group(n=20),spleen invigorating group(n=20)and heat clearing group(n=20).Except the normal group,diethylnitrosamine induced liver cancer model was used in the other three groups.Starting from the 12th week of modeling,Jianpi group and Qingre group were given corresponding liquid medicine at a dose of 1ml/100g,once per day for 12 weeks.Normal group and model group were given normal saline at the same dose.Observe the general situation of rats;Hematoxylin-eosin staining was used to observe liver histopathology.The expression of IL-6,TNF-a,TGF-β1,CXCL12,CXCR4 in liver tissue was detected by inmunohistochemistry.SPSS 20.0 software was used to analyze the experimental data and compare the effects of each group on the microenvironment of liver cancer.Results:1.Study on medication rule:(1)Among the commonly used drugs for liver cancer mainly treated by invigorating spleen and invigorating qi,the top 10 are Atractylodes macrocephala Koidz(100),Poria cocos(89),Astragalus membranaceus(75),Codonopsis pilosula(59),Glycyrrhiza uralensis(50).Coix seed(50),Dried tangerine(47),Malt(45),Hedyotis diffusa(44),Bupleurum chinense(42).(2)Among the drugs mainly treating liver cancer with the method of invigorating spleen and qi,warm drugs(668 times),cold drugs(611 times)and peaceful drugs(522 times)are used most frequently.followed by cool drugs(106 times).and hot drugs(6 times)are used least frequently.(3)Among the drugs for liver cancer mainly treated by invigorating spleen and qi,sweet drugs(1101 times)are used most frequently,followed by bitter drugs(922 times)and pungent drugs(637 times),sour drugs(139 times),salty drugs(104 times)and astringent drugs(65 times)are used relatively infrequently.(4)Based on the statistical results of traditional chinese medicine auxiliary inheritance platform,the drugs entering spleen meridian are the most,followed by drugs entering liver meridian.(5)Based on the analysis of association rules,28 common drug combinations were found in the included prescriptions.Among them,drug combinations containing Atractylodes macrocephala accounted for 50%(14 in total).Among them,the combination with the highest confidence level is dangshen-poria cocos-atractylodes macrocephala koidz.(6)Using unsupervised entropy hierarchical clustering algorithm,Seven new prescriptions for treating liver cancer were finally obtained.2.Animal experiment:(1)Compared with the model group,the expressions of CXCL12 and CXCR4 in spleen-strengthening group and heat-clearing group are decreased,and the degree of decrease in spleen-strengthening group is more obvious,with significant difference between the model group(P<0.01),while the difference between heat-clearing group and model group is not significant(P>0.05).Compared with the heat-clearing group.the expression of CXCL12 and CXCR4 in the spleen-strengthening group was significantly lower than that in the heat-clearing group,with obvious difference(P<0.01).(2)Compared with the model group,the expressions of IL-6,TNF-a and TGF-beta 1 in the spleen-invigorating group and heat-clearing group were all decreased,and the expressions of IL-6,TNF-a and TGF-beta 1in the spleen-invigorating group were significantly lower than those in the model group(P<0.01);the expressions of IL-6 and TGF-beta in the heat-clearing group were significantly lower than th ose in the model group(P<0.01),while the levels of TNF-a were not significantly lower(P>0.05).Compared with the Qingre group,the expressions of IL-6,TNF-a and TGF-beta 1 in the Jianpi group were lower than th ose in the Qingre group,but there was no significant difference between the two groups(P>0.05).Conclusion:1.Among the prescriptions for hepatocellular carcinoma treated mainly by invigorating spleen and invigorating qi,Atractylodes macrocephala is the core drug;"Atracty lodes macrocephala-Poria cocos" is the most used combination of drugs."Codonopsis pilosula-Poria cocos-atractylodes macrocephala"is a highly correlated drug combination;Ganwei medicine and bitter medicine are used together,cold medicine and warm medicine are used together and liver-spleen coordination are the important principles followed by clinical prescriptions.The above results have certain reference value for clinical drug selection and prescription optimization.2.The method of invigorating spleen and qi is an effective treatment for liver cancer by traditional Chinese medicine.It can effectively adjust the levels of chemokines(CXCL12,CXCR4),cytokines(IL-6,TNF-a,TGF-(β1)in the microenvironment of liver cancer.and has the effects of inhibiting tumor growth and delaying the development of liver cancer.