摘要
目的研究晶V型芒果苷对高尿酸血症小鼠的作用及其机制。方法 70只昆明小鼠随机分成正常对照组、模型组、别嘌呤醇组(25 mg·kg^(-1))、苯溴马隆组(25 mg·kg^(-1))、晶V型芒果苷低、中、高剂量组(10、30、100 mg·kg^(-1))。正常组给予CMC-Na溶液,其余各组连续腹腔注射氧嗪酸钾21 d(300 mg·kg^(-1)),d 8起各组给予相应药物。造模d 21给药后,各组小鼠取血,肝肾称重以计算脏器指数,测定血清生化指标,HE染色观察肾脏病理损伤,检测肾、肠转运体相关mRNA水平、肝黄嘌呤氧化酶活性和mRNA表达水平。结果晶V型芒果苷组能明显降低高尿酸血症小鼠血尿酸水平,肝肾指数和生化指标无明显改变,适度改善模型小鼠肾脏病理变化。机制研究显示,晶V型芒果苷能抑制黄嘌呤氧化酶的活性和表达,降低肾脏和肠道GLUT9的基因表达,调节PDZK1的表达。结论晶V型芒果苷可有效降低高尿酸血症小鼠的血尿酸水平,改善肾功能,且对小鼠肝肾无损伤。
Aim To investigate the pharmacological effects of mangiferin(crystalⅤ)on the hyperuricemia mice induced by potassium oxonate and its mechanism.Methods Male 70 Kunming mice were randomly divided into normal control group,model group,allopurinol group(25 mg·kg-1),benzbromarone group(25 mg·kg-1),mangiferin(crystalⅤ)low(10 mg·kg-1),middle(30 mg·kg-1),and high(100 mg·kg-1)dose groups.The control group received intraperitoneal injection of CMC-Na solution,and the other groups of oteracil potassium(300 mg·kg-1,i.p.)for 21 d.From day 8 to day 21 different groups were treated with different drugs.Blood,liver,kidney were taken and weighted at the end of experiment.Serum biochemical parameters,renal and intestine uric acid transporter mRNA expression,hepatic xanthine oxidase activity and mRNA expression were measured,and renal HE staining was performed.Results Mangiferin(crystalⅤ)decreased significantly serum uric acid level,inhibiting the hepatic magnesium oxide(XO)activity.There was no obvious change in liver,kidney index and biochemical index.Further mechanism studies showed that mangiferin(crystal V)inhibited GLUT9 mRNA expression in kidney and intestine,regulated the expression of PDZK1,and improved renal pathological changes.Conclusion Mangiferin(crystalⅤ)can remarkably reduce hyperuricbemia and improve the renal function in mice with hyperuricemia,without liver and kidney toxicity.
作者
杨海光
周启蒙
王海港
程笑
赵晓悦
吕扬
方莲花
杜冠华
YANG Hai-guang;ZHOU Qi-meng;WANG Hai-gang;CHENG Xiao;ZHAO Xiao-yue;LYU Yang;FANG Lian-hua;DU Guan-hua(Beijing Key Lab of Drug Targets Identification and Drug Screening,Instiute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Beijing Key Lab of Polymorphic Drugs, Instiute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2018年第10期1356-1362,共7页
Chinese Pharmacological Bulletin
基金
中国医学科学院医学与健康科技创新工程(No 2017-I2M-1-010)
国家重点研发计划专项(No 2016YFC1000900)
关键词
晶型
芒果苷
高尿酸血症
尿酸转运体
氧嗪酸钾
黄嘌呤氧化酶
crystalline form
mangiferin
hyperuricemia
oteracil potassium
magnesium oxide
xanthine oxidase
