Effect And Mechanism Of Probiotics On Serum Uric Acid Levels In Mice With Hyperuricemia

Part? Effect and mechanism of probiotics on serum uric acid level in a C57 BL / 6 mouse model with primary hyperuricemiaObjective: To detect the changes of intestinal microflora in hyperuricemia,and the effect and mechanism of probiotics on serum uric acid and ABCG2 / BCRP.Methods: 1.To construct urate oxidase(Uricase,Uox)gene knockout C57 BL / 6 mice hyperuricemia model,using Real-time PCR and Western-blot to verify the knockdown efficiency;2.Mice were divided into 4 groups(n = 12).Normal group: normal control C57 BL / 6 mice were administered with 0.2 ml normal saline;High uric acid group: Uox gene knockout C57 BL / 6 mice were administered with 0.2 ml normal saline group;Normal group + probiotics group(probiotics N group): normal C57 BL / 6 mice were administered probiotics(respectively containing Bifidobacterium and Lactobacillus 1 ×106CFU,dissolved in 0.1 ml saline);High uric acid group + probiotics group(probiotics H group): Uox gene knockout C57 BL / 6 mice were administered with probiotics(respectively containing Bifidobacterium and Lactobacillus 1 × 106 CFU,dissolved in 0.1ml saline).3.Total DNA were extracted from mice feces samples,16 S r RNA specific primers were designed based on absolute quantitative RT-PCR for the detection of intestinal bacteria especially Lactobacillus and Bifidobacterium;Automatic biochemical analyzer and detection kit were used to detect the serum uric acid(UA)and endotoxin(LPS)and xanthine oxidase activity(XO);RT-PCR and Western-blot were used to detect the expression of m RNA and protein of mice intestinal urate transporter ABCG2 / BCRP;Enzyme colorimetry was used to detect the intestinal flora of UA decomposition level.To detect the above indicators on 0,7,14,21,28 and 35 days.4.SPSS17.0 software was used for statistical analysis.Results: Compared with the normal group,the number of bifidobacteria and lactobacilli in the intestinal tract of the primary hyperuricemia mice was significantly decreased(P <0.05),which was induced by Uox gene knockout.Serum uric acid,endotoxin and xanthine oxidase activity were significantly increased(P < 0.01).The expression of intestinal urate transporter ABCG2 / BCRP was increased(P < 0.05);Lactobacillus and Bifidobacterium in the treatment of hyperuricemia in mice for five weeks,the number of primary hyperuricemia in mice intestinal bifidobacteria and lactobacillus were significantly increased(P < 0.05).The levels of serum uric acid,endotoxin and xanthine oxidasewere significantly lower than those of the control group(P < 0.01),but there was no significant difference in the expression level of ABCG2 / BCRP.Conclusion: On the one hand,probiotics can restore the balance of primary hyperuricemia mice intestinal flora,the intestinal probiotics Lactobacillus and Bifidobacterium were increased and the number of circulating UA,LPS and XO activity were decreased;On the other hand,probiotics can increase intestinal UA decompose level leading to increased intestinal excretion of uric acid.After all,probiotics can reduce the level of serum UA in primary hyperuricemia model mice by the above methods.Part? The effect and mechanism of probiotics on serum uric acid level in rotavirus gastro-enteritis mouse modelObjective: Gastroenteritis(gastro-enteritis,GE)in children with rotavirus(rotavirus,RV)may be associated with hyperuricemia.Therefore,we established the RV GE mouse model,and then detected the level of serum uric acid(Uric Acid,UA),and the change of the expression of ABCG2 / BCRP.At the same time,probiotics Lactobacillus and Bifidobacterium were used to treat RV GE mice,and then to observe the changes of serum UA and the expression of ABCG2 / BCRP.Methods: GE RV mice model was established by intragastric administration of RV.Mice were randomly divided into 4 groups: Normal group,RV GE group,Probiotics N group and Probiotics RV group.RV GE group and probiotics RV group were given intragastric administration of 0.2 ml medium which contains RV(2 x108PFU),the normal group and probiotics N group were given 0.2 ml medium without RV.The probiotics RV group and probiotics N group were given intragastric administration of probiotics(respectively containing Bifidobacterium 1 x 106 and Lactobacillus CFU,dissolved in 0.1 ml saline)every day following the intragastric administration of 0.2 ml medium.At the same time,the normal group and RV GE group were given 0.1 ml saline.The serum levels of UA were detected by automatic biochemical analyzer.The expression of m RNA in intestinal uric acid transporter ABCG2 / BCRP was detected by RT-PCR assay.We detected the above indicators on 1,2,3,4,5,6,7 and 10 days.Results: Compared with the normal group,serum UA level in both RV GE group and probiotics group RV were significantly increased on 3,5,6,7,10 days(P < 0.01),the level of serum UA in probiotics N group had no differences;Compared with RV GE group,the serum UA level in probiotics N group were significantly decreased on 4,5,6,7,and 10 days(P < 0.01),the serum UA level of probiotics RV group were significantly decreased on 3,4,5,6,7,10 days(P < 0.05),but the value at each time point is still higher than those of the normal group(P < 0.05).Compared with the normal group,the m RNA level expression of intestinal urate transporter ABCG2 / BCRP in RV GE group were significantly increased on 3,4,5,6,7,10 day(P < 0.05),the m RNA level expression of intestinal urate transporter ABCG2 /BCRP in probiotic N group showed no significant difference between the group of ABCG2 / BCRP m RNA,the m RNA level expression of intestinal urate transporter ABCG2 / BCRP in probiotics was decreased at each time and showed significant difference on 2,3,4 day(P < 0.05);Compared with RV GE group,the m RNA level expression of intestinal urate transporter ABCG2 / BCRP in probiotics N group was significantly increased on 3,4,5,6,7,10 day(P < 0.05),the m RNA level expression of intestinal urate transporter ABCG2 / BCRP in the probiotics RV group was increased and had statistically significant difference on 3,4,5,6,7,10 day(P < 0.05),but the value at each time point is still lower than those of the normal group.Conclusion: In our exprimental report,we found that RV GE is accompanied by hyperuricemia.The main reason of that may involved the following fact: RV destroys the intestinal epithelial cells,and the expression of intestinal UA transporter ABCG2 / BCRP in epithelial cells is decreased.After all,the level of serum UA is increased as followed.At the same time,probiotics treatment can increase the level of serum UA excretion by increasing the expression of ABCG2 / BCRP,which leads to the decrease of serum UA level.