| Objective To investigate the intestinal microecological changes and related mechanisms undergone transcatheter arterial chemoembolization(TACE)in New Zealand rabbits with VX2 hepatic tumor implantation.Methods Twenty-four New Zealand rabbits were randomly divided into normal control group(n=6)and liver cancer group(n=18).The liver cancer group were randomly divided into 3 subgroups,including 1 day,5 days,and 10 days after TACE(n=6,in each subgroup).The TACE were operated when CT scan shows tumors grow around 2 cm in diameter.Serum and stool samples were collected at 1 day before TACE,1 day,5 day and 10 days after TACE.Then the animals were executed euthanasia at 1 day,5 day and 10 days after TACE.Tissue,stool,and serum samples were then tested.Results The disorder degree of gut microbiota reached the maximum at one day after TACE.We also found that the intestinal bacterial diversity of the tumor group was lower than the control group.Serum DAO,D-LA,LPS,and TLR4 were significantly increased in VX2 liver cancer model of 1 day before TACE(P<0.05),and also increased in 1 day after TACE compared with the control group.The blood serum index of 5 days and 10 days after TACE were decreased.The value in 10 days after TACE was lower than that before TACE(P < 0.05).Pearson correlation analysis showed that there was correlation between ALT and DAO,DAO and LPS,ALT and LPS(The r values were 0.48,0.82 and 0.68 respectively,P < 0.05).Analysis between gut microbiota and clinical factors showed that the pathogenic bacteria increased in group 1 d after operation,and the pathogenic bacteria in group 10 d was lower than 1 day before operation.The expression of TLR4,p-STAT3 and COX-2 in tumor tissues showed the highest expression at 1 d after operation,and the expression at 10 d was lower than that at 1 d after operation,which was higher than that of the normal control group.The tumor tissues were tested by Western-Blot showed that the relative expression levels of p-NF-?B and p-STAT3,COX-2,and TLR4 were highest at 1 d after operation.The 10 d group was lower than the 1 d group,higher than the control group.Conclusion The rabbit VX2 liver tumor model has stable growth traits and could be used for related research in TACE liver cancer model.TACE treatment can improve intestinal barrier function,reduce blood LPS,down-regulate TLR4 level,and improve the prognosis of tumor treatment in VX2 liver cancer model compared with the control group.In the clinical treatment of liver cancer,the gut microbiota disorder of animal model after TACE showed dynamic changes.Among the dynamic changes of the gut microbiota,many strains were related to clinical factors,and there was a law of change about worse,recovery of disorders and better.The relative expression levels of p-NF-?B and p-STAT3,COX-2,and TLR4 were significantly decreased at the 10 days after operation.The gut microbiota may affect liver tumor tissues via this signal path. |
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