高尿酸血症(hyperuricemia, HUA)的临床用药毒副作用大,益生菌作为一种天然的安全食品,可以辅助治疗HUA。该研究旨在探究益生菌缓解HUA及发挥肾脏保护的机制。格氏乳杆菌CCFM1346(5×109 CFU/g)活菌和死菌通过口服强饲法给予HUA模型小鼠3周。检测小鼠生理生化指标、肾脏病理学切片、肝组织黄嘌呤氧化酶(xanthine oxidase, XOD)和尿酸氧化酶(urate oxidase, UOX)活性以及肾脏转运蛋白、炎症小体和炎症因子的表达水平。结果表明,格氏乳杆菌CCFM1346活菌和死菌均显著降低小鼠血清尿酸水平,抑制肝脏XOD活性,并促进肝脏UOX活性(P<0.01)。HUA小鼠尿液中尿酸水平显著增加,肾脏重吸收交换蛋白的表达水平下调,排泄转运蛋白的表达水平上调(P<0.001)。活菌和死菌可以降低肾脏炎症小体NLRP3、ASC和Caspase-1以及炎症因子TNF-α、IL-1β和IL-6的mRNA表达(P<0.01)。格氏乳杆菌CCFM1346活菌和死菌通过调节尿酸代谢和改善肾脏炎症来缓解HUA。
Clinical drug treatment for hyperuricemia (HUA) has significant side effects.Probiotics, as natural and safe food supplements, can assist in treating HUA.This study aimed to explore the mechanisms by which probiotics alleviate HUA and provide kidney protection.Lactobacillus gasseri CCFM1346 (5×109 CFU/g) was administered to HUA model mice via oral gavage for 3 weeks.Physiological and biochemical parameters of mice, kidney histopathological sections, liver xanthine oxidase (XOD), and uricase (UOX) activities, as well as expression levels of kidney uric acid transporters, inflammasomes, and inflammatory factors, were examined.Results showed that both live and dead cells of L. gasseri CCFM1346 significantly decreased the serum uric acid levels in mice, inhibited liver XOD activity, and promoted liver UOX activity (P<0.01).Both live and dead cells significantly increased uric acid levels in the urine of HUA mice, downregulated expression of kidney reabsorption transporters, and upregulated expression of excretion transporters (P<0.001).Both live and dead cells reduced mRNA expression of NLRP3, ASC, and Caspase-1, and inflammatory factors TNF-α, IL-6, and IL-1β in kidney (P<0.01).L.gasseri CCFM1346 alleviates HUA by regulating uric acid metabolism and improving kidney inflammation.
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