短乳杆菌DM9218对高果糖饮食诱导的小鼠高尿酸血症的缓解作用及机制研究

The effect of Lactobacillus brevis DM9218 in relieving high fructose diet-induced hyperuricemia and the possible mechanisms

目的探讨短乳杆菌DM9218对高果糖饮食诱导的小鼠高尿酸血症的缓解作用及可能机制。方法 4~6周龄SPF级Balb/c雌鼠随机分为3组(每组15只),分别为正常对照组(Control)、高果糖饮水组(HF)、高果糖饮水+益生菌干预组(Probiotic)。高果糖组和益生菌干预组每天给予15%(w/v)果糖水自由饮用;益生菌干预组在果糖饮用的同时每天以0.2mL/只(1×109 CFU/kg)短乳杆菌DM9218灌胃,对照组和高果糖组予以0.2mL/只的PBS灌胃处理。采用酶标仪比色法检测各组血清中血糖(Glu)、甘油三酯(TG)、总胆固醇(TC)、血尿酸(UA)水平;ELISA法检测小鼠肝组织匀浆上清液中内毒素(LPS)、干扰素α(IFN-α)、肌苷(Inosine)水平及黄嘌呤氧化酶(XOD)浓度、活性;Q-PCR法检测XOD mRNA的表达变化。结果 HF组Glu、TG、TC、UA水平均明显高于Control组(P<0.05,P<0.05,P<0.05,P<0.01),Probiotic组血清UA水平显著低于HF组(P<0.01);HF组肝脏LPS、IFN-α、Inosine水平及XOD浓度、活性显著高于Control组(P均<0.01),Probiotic组与HF组相比LPS、IFN-α、Inosine水平及XOD浓度、活性有明显下降趋势,差异具有统计学意义(P<0.05,P<0.01,P<0.01,P<0.05,P<0.05);HF组XOD mRNA的相对表达量显著高于Control组(P<0.01),Probiotic组与HF组相比有下降趋势,差异具有统计学意义(P<0.01)。结论短乳杆菌DM9128一方面可以改善肠屏障功能降低LPS水平,从而缓解XOD的表达及活性;另一方面经由"肝-肠循环"直接降解肌苷,从而影响血清UA的水平。

Objective To explore the possible mechanisms of Lactobacillus brevis DM9218 in relieving high fructose diet-induced hyperuricemia in mice.Methods Four-to six-week-old Balb/c SPF female mice were randomly divided into 3 groups（15 mice per group）：high fructose（HF）group,high fructose＋probiotic intervention（Probiotic）group and control（Control）group respectively.The HF group and Probiotic group were given 15%（w/v）fructose for drinking freely;the Probiotic group were additionally administered 1×10~9 CFU/kg Lactobacillus brevis DM9218 intragastrically once a day.The mice in the Control and HF groups were administered 0.2 mL of PBS as vehicle.The levels of glucose（Glu）,triglyceride（TG）,total cholesterol（TC）and serum uric acid（UA）were measured by using enzyme colorimetry kits.The levels of serum endotoxin（LPS）,interferonα（IFN-α）and inosine,as well as the concentration and activity of xanthine oxidase（XOD）in the supernatant of liver homogenate were detected with ELISA.The relative expression of XOD mRNA was detected with Q-PCR.Results The levels of Glu,TG,TC and UA in HF group were significantly higher than those in Control group（P0.05,P0.05,P0.05,P0.01）,and the level of UA in Probitic group was significantly lower than that in HF group（P0.01）.Compared to the Control group,the levels of LPS,IFN-αand inosine,as well as the concentration and activity of XOD in the liver of the HF group significantly increased（Ps0.01）.Compared to the HF group,the levels of LPS,IFN-αand inosine,as well as the concentration and activity of XOD in Probiotic group significantly decreased（P0.05,P0.01,P0.01,P0.05,P0.05）.The relative expression of XOD mRNA in HF group was significantly higher than that in Control group（P0.01）.Compared with HF group,the relative expression of XOD mRNA in Probiotic group showed a decreasing trend with statistically significant difference（P0.01）.Conclusion Lactobacillus brevis DM9128 can improve the intestinal barrier function and reduce the expression and activity of XOD.On the other hand,it can directly degrade inosine through the ＂ hepatic-intestinal axis＂,thus affecting the level of serum UA.