四妙散加味对高尿酸血症大鼠尿酸代谢及肠道菌群的影响

Effects of Modified Simiaosan on uric acid metabolism and gut microbiota in rats with hyperuricemia

目的观察四妙散加味对高尿酸血症大鼠尿酸代谢及肠道菌群的影响。方法将60只SD大鼠随机分为生理盐水组、模型组、苯溴马隆组、四妙散加味低、中、高剂量组各10只。酵母膏10g/(kg·d)+腺嘌呤100mg/(kg·d)灌胃造模,6h后灌胃干预药物,21d后用全自动酶标仪检测血清尿素氮(BUN)、肌酐(Cr)、黄嘌呤氧化酶(XOD)水平和血清、尿、粪尿酸(UA)含量,鲎试验偶氮基质显色法检测血清及盲肠内容物内毒素(LPS)活性,采用Illumina Miseq高通量测序平台对大鼠粪便样本中所有细菌的16s rRNA V3-V4区进行DNA测序,分析肠道菌群物种的多样性(Shannon指数)与丰度。结果模型组大鼠血BUN、Cr、XOD、UA水平及血清、盲肠内容物中LPS含量和拟杆菌属丰度值高于生理盐水组,尿、粪UA含量及Shannon指数和乳酸杆菌属丰度值低于生理盐水组,差异有显著统计学意义(P<0.01)。四妙散加味中剂量组血BUN、Cr、XOD、UA水平及血液、盲肠内容中LPS含量和拟杆菌属丰度值低于模型组、苯溴马隆组,粪尿酸含量及Shannon指数和乳酸杆菌属丰度值高于模型组、苯溴马隆组,差异有统计学意义(P<0.05或?<0.01)。结论四妙散加味能显著抑制HUA大鼠XOD活性,增加肾、肠尿酸排泄,减轻肠道炎症,降低拟杆菌属丰度,增加乳酸杆菌属丰度,改善HUA尿酸代谢和肠道菌群失调。

Objective To observe the effects of Modified Simiaosan on uric acid metabolism and gut microbiota in rats with hyperuricemia.Methods Sixty SD rats were randomly divided into saline group,model group,benbromarone group and low,medium and high dose groups of modified Simiaosan,with 10 rats in each group.Except for saline group,the other groups were given yeast extract 10 g/(kg·d)and adenine 100 mg/(kg·d)by gavage.Intervention drugs were given by gavage 6 h later.The levels of blood urea nitrogen(BUN),creatinine(Cr),xanthine oxidase(XOD),and uric acid(UA)in serum,urine and feces were detected by automatic microplate reader 21 days later.The activities of lipopolysaccharide(LPS)in serum and cecal contents were detected by limulus test azo matrix chromogenic method.The Illumina Miseq high-throughput sequencing platform was used to analyze DNA sequencing of the 16 S rRNA V3-V4 regions of all bacteria in rat fecal samples,the species diversity(Shannon)and abundance of gut microbiota were analyzed.Results Compared with saline group,the contents of blood urea nitrogen,creatinine,xanthine oxidase,uric acid and lipopolysaccharide in blood and cecum contents,the abundance value of Bacteroides in model group were increased,while the contents of uric acid in urine and feces,indexes of Shannon,the abundance of were decreased.The difference between the two groups was statistically significant(P<0.01).Compared with model group and benbromarone group,the contents of blood urea nitrogen,creatinine,xanthine oxidase,uric acid and lipopolysaccharide in blood and cecum,the abundance value of Bacteroides in the medium dose group of modified Simiaosan were lower,while the contents of uric acid in feces,index of Shannon,the abundance of were significantly higer(P<0.05 or P<0.01).Conclusion Modified Simiaosan can significantly inhibit the activity of uric acid oxidase of rats with hyperuricemia,increase uric acid excretion in renal and intestinal,alleviate gut inflammation,reduce the abundance value of,increase the abundance value of,thus improve uric acid metabolism and ameliorate gut microbiota imbalance.