天麻素对次黄嘌呤诱导小鼠急性高尿酸血症的影响和机制研究

摘要
图/表
参考文献(21)
相关文章 (15)

全文: PDF (0 KB) HTML (40 KB)
输出: BibTeX | EndNote (RIS)

摘要目的探讨天麻素（GAS）对次黄嘌呤诱导的小鼠急性高尿酸血症（HUA）的影响及可能机制。方法雄性昆明种小鼠50 只随机分为5 组，分别为正常组、模型组、GAS 200 mg/kg 组、GAS 400 mg/kg 组和别嘌呤醇（ALLO）10 mg/kg 组，每组10 只。灌胃给药14 d，于末次给药1 h 后除正常组外其余各组动物腹腔注射次黄嘌呤1000 mg/kg。注射45 min 后取血测定血清生化指标。动物处死后取肝脏以试剂盒测定黄嘌呤氧化酶（XOD）活力，并取肾脏提取RNA，反转录后以实时荧光定量PCR 检测尿酸盐转运蛋白1（URAT1）和有机阴离子转运蛋白1（OAT1）的mRNA 表达水平。结果模型组动物血清尿酸（UA）水平和肝脏XOD 活力高于正常组，肾脏URAT1 的mRNA 表达水平高于正常组，而OAT1 的mRNA 表达水平低于正常组，差异有统计学意义（P＜0.01 或P＜0.001）。剂量为200 mg/kg和400 mg/kg 的GAS 使小鼠血清UA 水平下降，同时使肝脏XOD 活力减少，肾脏URAT1 的mRNA 表达水平下降而OAT1 的mRNA 表达水平增加（与模型组比较，P＜0.05 或P＜0.01）。ALLO 使上述指标均恢复正常（与模型组比较，P＜0.01 或P＜0.001）。结论 GAS 可能通过抑制肝脏XOD 活力、下调肾脏URAT1 的mRNA 表达和上调肾脏OAT1 的mRNA 表达来改善次黄嘌呤诱导的小鼠急性HUA。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	褚亚慧
	孔维佳

关键词 ：天麻素, 高尿酸血症, 别嘌呤醇, 黄嘌呤氧化酶, 尿酸盐转运蛋白1, 有机阴离子转运蛋白

Abstract：Objective To study the effects and possible mechanisms of gastrodin(GAS)on acute hyperuricemia(HUA)of mice induced by hypoxanthine.Methods A total of 50 male Kunming mice were randomly divided into five groups,which included the normal group,the model group,GAS 200 mg/kg group,GAS 400 mg/kg group,and allopurinol(ALLO)10 mg/kg group.There were 10 mice in each group,and the drugs were intragastricaly administered for 14 days.One hour after the last drug administration,mice were intraperitoneally injected with hypoxanthine at a dose of 1000 mg/kg,except for the normal group.Blood samples were collected for the assay of serum biochemical parameters 45 minutes after the injection.The animals were then sacrificed,and their livers were harvested for the determination of xanthine oxidase(XOD)activity by a kit.The kidneys were also collected for RNA extraction,and after reverse transcription,the mRNA expression levels of urate transporter 1(URAT1)and organic anion transporter 1(OAT1)were determined by quantitative real-time PCR.Results The serum uric acid(UA)level and liver XOD activity of the model group were higher than that of the normal group,the mRNA expression level of URAT1 in the kidney was higher than that of the normal group,while the mRNA expression level of OAT1 was lower than that of the normal group,the differences were statistically significant(P＜0.01 or P＜0.001).Administration of 200 mg/kg and 400 mg/kg of GAS decreased serum UA of the mice.Meanwhile,they also reduced liver XOD activity,decreased renal URAT1 mRNA expression level and increased that of OAT1(P＜0.05 or P＜0.01 compared to model group).ALLO restored the above parameters to normal(P＜0.01 or P＜0.001 compared to model group).Conclusion GAS improves acute HUA of mice induced by hypoxanthine,which may be attributable to inhibition of liver XOD activity,down-regulation of renal URAT1 mRNA expression,and up-regulation of renal OAT1 mRNA expression.

Key words： Gastrodin Hyperuricemia Allopurinol Xanthine oxidase Urate transporter 1 Organic anion transporter 1

作者简介: 褚亚慧（1996-），女，中国医学科学院北京协和医学院2019 级药理学专业在读硕士研究生，研究方向：代谢性疾病药理学。

引用本文:

褚亚慧；孔维佳. 天麻素对次黄嘌呤诱导小鼠急性高尿酸血症的影响和机制研究[J]. 中国当代医药, 2021, 28(26): 23-26.
CHU Ya-hui ；KONG Wei-jia. Study of the effects and mechanisms of gastrodin on acute hyperuricemia of mice induced by hypoxanthine. 中国当代医药, 2021, 28(26): 23-26.

链接本文:

http://dangdaiyiyao.com/CN/ 或 http://dangdaiyiyao.com/CN/Y2021/V28/I26/23

[1]	Zhan HD，Zhou HY，Sui YP，et al.The rhizome of Gastrodia elata Blume-An ethnopharmacological review[J].J Ethnopharmacol，2016，189：361-385.
[2]	Qian L，Yan S，Li Y，et al.The effects of gastrodin injection on hypertension：A systematic review and meta-analysis[J].Medicine（Baltimore），2020，99（27）：e20936.
[3]	Zhao S，Li N，Zhen Y，et al.Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats[J].Food Chem Toxicol，2015，86：202-207.
[4]	王灿，于滨，孔维佳.天麻和天麻素改善糖脂代谢紊乱的药理学研究进展[J].中国医药导报，2016，13（27）：51-54.
[5]	Ma JQ，Sun YZ，Ming QL，et al.Effects of gastrodin against carbon tetrachloride induced kidney inflammation and fibrosis in mice associated with the AMPK/Nrf2/HMGB1 pathway[J].Food Funct，2020，11（5）：4615-4624.
[6]	Lee SJ，Oh BK，Sung KC.Uric acid and cardiometabolic diseases[J].Clin Hypertens，2020，26：13.
[7]	Siemińska E，Sobczak P，Skibińska N，et al.The differential role of uric acid-The purpose or cause of cardiovascular diseases[J].Med Hypotheses，2020，142：109791.
[8]	吴宝金，秦川，孔琪，等.实验动物教学用动物使用指南[S].北京：中国实验动物学会，2017，T/CALAS 29-2017.
[9]	郑志萍，黄幼霞.小鼠高尿酸血症模型的建立[J].海峡药学，2011，23（9）：27-29.
[10]	张艳玲，蒋建东，孔维佳.丁酸钠与小檗碱联合改善C57BL/6J 小鼠非酒精性脂肪性肝病[J].中国药理学通报，2019，35（12）：1664-1670.
[11]	Chen Y，Zhao Z，Li Y，et al.Baicalein alleviates hyperuricemia by promoting uric acid excretion and inhibiting xanthine oxidase[J].Phytomedicine，2021，80：153374.
[12]	曹韦，陈小鹏，刘娜，等.天麻素对过氧化氢损伤大鼠原代皮层神经元保护作用研究[J].亚太传统医药，2016，12（24）：17-20.
[18]	吴志明，郭健，祝小波.非布司他和苯溴马隆控制痛风的疗效与安全性Meta 分析[J].实用临床医学，2020，21（4）：1-4.
[21]	郑洋洋，董志，路晓钦，等.315 例天麻素临床不良反应/事件分析[J].中国中药杂志，2015，40（10）：2037-2041.
[13]	Arakawa H，Amezawa N，Katsuyama T，et al.Uric acid analogue as a possible xenobiotic marker of uric acid transporter Urat1 in rats[J].Drug Metab Pharmacokinet，2019，34（2）：155-158.
[14]	Wang Z，Cui T，Ci X，et al.The effect of polymorphism of uric acid transporters on uric acid transport[J].J Nephrol，2019，32（2）：177-187.
[15]	Dong Y，Zhao T，Ai W，et al.Novel urate transporter 1（URAT1）inhibitors：a review of recent patent literature（2016-2019）[J].Expert Opin Ther Pat，2019，29（11）：871-879.
[16]	Lee HA，Yu KS，Park SI，et al.URC102，a potent and selective inhibitor of hURAT1，reduced serum uric acid in healthy volunteers[J].Rheumatology（Oxford），2019，58（11）：1976-1984.
[17]	Strilchuk L，Fogacci F，Cicero AF.Safety and tolerability of available urate-lowering drugs：a critical review[J].Expert Opin Drug Saf，2019，18（4）：261-271.
[19]	Pui K，Gow PJ，Dalbeth N.Efficacy and tolerability of probenecid as urate-lowering therapy in gout;clinical experience in high-prevalence population[J].J Rheumatol，2013，40（6）：872-876.
[20]	Zhang Z，Ma P，Xu Y，et al.Preventive effect of gastrodin on cognitive decline after cardiac surgery with cardiopulmonary bypass：a double -blind，randomized controlled study[J].J Huazhong Univ Sci Technolog Med Sci，2011，31（1）：120-127.