中药新药与临床药理2025,Vol.36Issue(9):1450-1457,8.DOI:10.19378/j.issn.1003-9783.2025.09.005
健脾化湿泄浊方对高尿酸血症大鼠的作用及机制
Effects and Mechanisms of Jianpi Huashi Xiezhuo Formula on Hyperuricemic Rats
摘要
Abstract
Objective To investigate the effects and mechanisms of Jianpi Huashi Xiezhuo Formula(JPHSXZF)on hyperuricemia(HUA)rats.Methods Male SD rats were randomly divided into four groups(n=10 per group):blank control group,model group,JPHSXZF group(11.88 g·kg-1),and benzbromarone group(7.24 mg·kg-1).A HUA model was established by oral administration of 200 mg·kg-1 ethambutol plus 600 mg·kg-1 potassium oxonate for 3 weeks.The JPHSXZF and benzbromarone groups received their respective treatments,while the blank and model groups received equal volumes of saline,once daily for 3 weeks.Model induction conditions were maintained throughout the treatment period.Serum uric acid(UA)levels were measured using the enzymatic colorimetric method.Hepatic and renal histopathological changes were evaluated by HE staining.The mRNA expression levels of ATP-binding cassette subfamily G member 2(ABCG2)and glucose transporter 9(GLUT9)in the small intestine,as well as urate transporter 1(URAT1)and organic anion transporter 1(OAT1)in the kidneys,were detected by qPCR.Protein expression levels of ABCG2,GLUT9,URAT1,and OAT1 were analyzed by Western Blot.Renal ABCG2 protein expression was further confirmed by immunofluorescence.Results Compared with the blank group,the model group exhibited significantly elevated serum UA levels(P<0.05),vacuolar degeneration of glomerular epithelial cells,and tubular epithelial cell necrosis.Small intestinal ABCG2 mRNA and protein expression were downregulated(P<0.05),while GLUT9 expression was upregulated(P<0.05).Renal OAT1 mRNA expression was downregulated(P<0.05),whereas URAT1 mRNA expression was upregulated(P<0.05).Renal ABCG2 protein expression was also downregulated(P<0.05).Compared with the model group,all treatment groups showed significantly reduced serum UA levels(P<0.05),alleviated glomerular and tubular damage,upregulated mRNA and protein expression of small intestinal ABCG2 and renal OAT1(P<0.05),downregulated mRNA and protein expression of small intestinal GLUT9 and renal URAT1 expression(P<0.05),and increased renal ABCG2 protein expression(P<0.05).Conclusion JPHSXZF reduces serum UA levels and exerts renal protective effects in HUA rats,likely by modulating urate transporter expression in the small intestine and kidneys,thereby inhibiting UA reabsorption and promoting its excretion.关键词
健脾化湿泄浊方/高尿酸血症/尿酸盐转运体蛋白/尿酸排泄/大鼠Key words
Jianpi Huashi Xiezhuo Formula/hyperuricemia/urate transporters/uric acid excretion/rats分类
医药卫生引用本文复制引用
王子旋,邱灵,陈冰燕,王美玲,张英杰,肖艳,陈鹏,苏友新,郭洁梅..健脾化湿泄浊方对高尿酸血症大鼠的作用及机制[J].中药新药与临床药理,2025,36(9):1450-1457,8.基金项目
国家重点研发计划"中医药现代化"重点专项(2022YFC3501200) (2022YFC3501200)
福建省财政专项(X2020004-财政专项) (X2020004-财政专项)
国家中医药管理局2021年岐黄学者支持项目[国中医药人教函(2022)No.6] (2022)
福建中医药大学苏友新岐黄学者传承工作室项目[闽中医(2023)No.56]. (2023)