Research On Synergism And Attenuation Effect Of Abnormal Savda Munziq On 5-FU

Objective: These study mainly discuss the synergism and attenuation action of Abnormal Savda Munziq（ASMq）to Fluorouracil（5-FU）,based on cancer transplanted mice model.Methods: To set up cervical cancer transplanted mice model,240 Kunming mice which were randomly divided in to 6 groups: control group,model group,5-FU group,5-FU(30mg·kg^-1)combine with ASMq(2g·kg^-1·d^-1)low-dose group,5-FU(30mg·kg^-1)combine with ASMq(4g·kg^-1·d^-1)medium-dose group,and 5-FU(30mg·kg^-1)combine with ASMq(8g·kg^-1·d^-1)high-dose group,different index measured in batches:（1）the inhibition rate of the cervical tumor in different dose of ASMq combined with 5-FU groups.The content of serum interleukin-2,interferon-γ,and tumor necrosis factor-α（TNF-α）were determined.Observing the morphology of tumor tissue in mice using HE staining.（2）The viscera indexes and the content of serum alanine aminotransferase（ALT）and aspartate aminotransferase（AST）were determined.The spleen T lymphocyte proliferation was evaluated by determined by MTT method.SOD,MDA,GSH-Px levels in liver and kidney tissues were determined,and observe the liver,kidney tissue pathological changes.（3）Using nuclear magnetic resonance（NMR）technology combined with pattern recognition analysis and orthogonal partial least-squares discriminant method,the difference of metabolites and the changes of the metabolic network in different dose groups with 5-FU ASMq combination of cervical cancer a tumor-burdened mice serum were determined.（4）The protein expression level of TGF –β1 and TNF-α in different dose groups with 5-FU ASMq combination in tumor tissues were detected by protein immunoblot method（western blot）method.Results:（1）The inhibitory rate of the 5-FU+ASMq.H group,5-FU+ASMq.M group,5-FU+ASMq.L group and 5-FU group were 77.29%,87.31%,69.93% and 77.29% respectively.Compared with tumor model group,IL-2,IFN-γ and TNF-α levels increase in 5-FU combine with ASMq each dose group mice serum（P<0.05）.Model group of tumors in invasive tumor growth and spread fast,boundaries between tumors and the surrounding adipose tissue is not obvious,but the boundaries of the tumor in 5-FU combined ASMq each dose group with the surrounding tissue were clear.The distribution of tumor model group is diffused,and the cell sizes were different.Tumor presented necrosis to varying degrees after treated by 5-FU combined ASMq.（2）Compared with normal control group,ALT and AST levels were higher in 5-FU group and 5-FU combined ASMq serum each dose group（P<0.05）;Compared with 5-FU group,ALT,AST were decreased in 5-FU combined ASMq each dose group of serum（P<0.05）.The lymphocyte proliferation ability of spleen T treated at the different time was enhanced（P<0.05）.Compared with 5-FU group,the liver,kidney tissues,SOD,GSH-Px levels in 5-FU combined ASMq each dose group were increased（P<0.05）;the MDA content in liver and kidney tissue in 5-FU combined ASMq dose group were significantly decreased（P<0.05）.Kidney tissue pathology results show that mild hyperemia in glomerular in 5-FU group,swelling and edema in the renal tubular epithelial cells,and congestion were noted in the lung interstitium.the renal tissue structure was normal and the edema was reduced in 5-FU combined with ASMq each dose group.Liver tissue pathology results show that in 5-FU group,the hepatic cells were generally swollen,with granular or eosinophilic changes,and the central vein was dilated and congested.The liver cell edema were alleviate in 5-FU combined with ASMq each dose group.（3）NMR results showed that compared with the normal control group,the lipid,glycoprotein,acetone,carnitine,low density lipoprotein,unsaturated lipid content in serum tumor model group mice were increasing,the content of isoleucine,valine,alanine,lactic acid,acetic acid,pyruvic acid,citric acid,glutamine,glycine,1-methyl histidine,creatine and other metabolites decreased significantly（P<0.05）.Compared with the 5-FU control group,glycine,beta glucose,creatine content increased significantly,acetone,LDL,unsaturated lipid content in 5-FU combined ASMq each dose group of serum were decreased（P<0.05）.（4）Compared with the model group,the expression level of TGF^-1 protein was decreased and the expression level of TNF-protein was increased（P<0.05）in mice treated with 5-FU combined ASMq.Conlusion: The results suggested that ASMq might reduce toxicity and enhance the efficacy of the chemotherapeutic drug 5-fluorouracil in the treatment of cervical carcinoma.