藏药长花铁线莲及其主要成分calcoside D降低急性高尿酸血症小鼠尿酸水平及作用机制研究
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摘要
目的探讨长花铁线莲醇提物对急性高尿酸血症小鼠尿酸水平的影响及其主要成分降尿酸的作用机制。方法将70只昆明小鼠按体质量均衡随机分为空白组,急性高尿酸血症模型组,别嘌呤醇组(10 mg·kg~(-1)),长花铁线莲总提物高、低剂量组(2.34、1.17 g·kg~(-1)),calcoside D高、低剂量组(50、20 mg·kg~(-1)),每组10只,连续灌胃7 d,末次给药前30 min注射350 mg·kg~(-1)氧嗪酸钾造急性高尿酸血症模型。检测各组血清尿酸(UA)、肝脏黄嘌呤氧化酶(XOD)、肿瘤坏死因子(TNF-α)、白介素-1β(IL-1β)、尿素氮(BUN)含量及肝脏XOD、腺苷脱氨酶(ADA)活力,RT-PCR测定肾脏转运体mURAT1、mOAT1、mGLUT9 mRNA相对表达量。结果与模型组相比,长花铁线莲醇提物高、低剂量组和calcoside D高、低剂量组均能显著降低血清UA值与抑制肝脏XOD活力(P <0.05),calcoside D高、低剂量组能显著降低血清中BUN、IL-1β(P <0.05),calcoside D高剂量组能显著降低TNF-α的含量(P <0.05),calcoside D高、低剂量组均能抑制肝脏ADA活力(P <0.01),下调肾脏mURAT1(P <0.01)、上调mOAT1 mRNA(P <0.001)的表达,calcoside D低剂量组能显著下调mGLUT9 mRNA的表达(P <0.001)。结论长花铁线莲与calcoside D均具有显著降尿酸的作用,且calcosideD具有一定的肾脏保护作用和抗炎作用,抑制XOD与ADA活力及下调肾脏mURAT1、mGLUT9 mRNA的表达,上调mOAT1 mRNA的表达为calcoside D降尿酸的可能机制。
Objective To investigate the effect of ethanol extract of Clematis rehderiana Craib on uric acid level in mice with acute hyperuricemia and the mechanism of its active ingredient in reducing uric acid.Methods Seventy Kunming mice were randomly divided into 7 groups according to their weights,including blank group,acutely high uric acid model group,allopurinol group(10 mg·kg~(-1)),total extract of C.rehderiana high and low dose groups(2.34,1.17 g·kg~(-1)),calcoside D high and low dose groups(50,20 mg·kg~(-1)),10 mice in each group.The mice were continuously intragastrically administered for 7 days,and the acute hyperuricemia model was induced by injection of 350 mg·kg~(-1)potassium oxonate 30 min before the last administration.Serum uric acid(UA),hepatic xanthine oxidase(XOD)levels in the C.rehderiana total extract groups,and serum UA,tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),urea nitrogen(BUN)content and liver XOD,adenosine deaminase(ADA)activity,relative expression of renal transporter mURAT1,mOAT1,and mGLUT9 mRNA in the caloside D groups were detected.Results Compared with the model group,the high and low dose groups of C.rehderiana Craib ethanol extract and the high and low dose group of calcoside D can significantly reduce the serum UA level and inhibit the activity of liver XOD(P<0.05);and the calcoside D high and low dose groups can significantly decrease the serum levels of BUN and IL-1β(P<0.05).The high dose of calcoside D could significantly reduce the content of TNF-α(P<0.05).The high and low doses of calcoside D could inhibit the activity of liver ADA(P<0.01)and down-regulate the mURAT1 in kidney tissue(P<0.01),up-regulated the expression of mOAT1mRNA(P<0.001).Low dose of calcoside D significantly down-regulated the expression of mGLUT9 mRNA in kidney tissue(P<0.001).Conclusion Both C.rehderiana Craib ethanol extract and calcoside D have significant UA lowering effects,and calcoside D has renal protective and anti-inflammatory effects,inhibits XOD and ADA activities,down-regulates mURAT1 and mGLUT9 mRNA expression in the kidney,and up-regulates mOAT1mRNA expression,which is the possible mechanism of UA lowering.
Objective To investigate the effect of ethanol extract of Clematis rehderiana Craib on uric acid level in mice with acute hyperuricemia and the mechanism of its active ingredient in reducing uric acid.Methods Seventy Kunming mice were randomly divided into 7 groups according to their weights,including blank group,acutely high uric acid model group,allopurinol group(10 mg·kg~(-1)),total extract of C.rehderiana high and low dose groups(2.34,1.17 g·kg~(-1)),calcoside D high and low dose groups(50,20 mg·kg~(-1)),10 mice in each group.The mice were continuously intragastrically administered for 7 days,and the acute hyperuricemia model was induced by injection of 350 mg·kg~(-1)potassium oxonate 30 min before the last administration.Serum uric acid(UA),hepatic xanthine oxidase(XOD)levels in the C.rehderiana total extract groups,and serum UA,tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),urea nitrogen(BUN)content and liver XOD,adenosine deaminase(ADA)activity,relative expression of renal transporter mURAT1,mOAT1,and mGLUT9 mRNA in the caloside D groups were detected.Results Compared with the model group,the high and low dose groups of C.rehderiana Craib ethanol extract and the high and low dose group of calcoside D can significantly reduce the serum UA level and inhibit the activity of liver XOD(P<0.05);and the calcoside D high and low dose groups can significantly decrease the serum levels of BUN and IL-1β(P<0.05).The high dose of calcoside D could significantly reduce the content of TNF-α(P<0.05).The high and low doses of calcoside D could inhibit the activity of liver ADA(P<0.01)and down-regulate the mURAT1 in kidney tissue(P<0.01),up-regulated the expression of mOAT1mRNA(P<0.001).Low dose of calcoside D significantly down-regulated the expression of mGLUT9 mRNA in kidney tissue(P<0.001).Conclusion Both C.rehderiana Craib ethanol extract and calcoside D have significant UA lowering effects,and calcoside D has renal protective and anti-inflammatory effects,inhibits XOD and ADA activities,down-regulates mURAT1 and mGLUT9 mRNA expression in the kidney,and up-regulates mOAT1mRNA expression,which is the possible mechanism of UA lowering.
引文
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[15]梁文娟,和劲松,田洋,等.辣木叶提取物降低高尿酸血症小鼠尿酸水平及机理研究[J].安徽农业科学,2017,45(17):108-109.
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[2]闫曼,安雅婷,李舰,等.益母草提取物对大鼠高尿酸血症的调控作用[J].中国中药杂志,2014,39(24):4856-4859.
[3]杜格,蒋雨彤,古洁若.降尿酸药物研究进展[J].新医学,2017,48(6):369-374.
[4]宇妥·云丹贡布.四部医典[M].北京:人民卫生出版社,1983:25-26.
[5]罗达尚.新修品珠本草[M].成都:四川科学技术出版社,2004:254-257.
[6]杨永昌.藏药志[M].西宁:青海人民出版社,1991:248-249.
[7]张欢欢.复方土茯苓颗粒治疗HUA疗效及对HK-2细胞miR-34a、URAT1表达的影响[D].广州:广州中医药大学,2014.
[8]王宝勤.国家藏药标准全书[M].北京:中华医学电子音像出版社,2004:101-102
[9]王晓云,王洪玲,张亚梅,等.西伯利亚蓼醇提物对高尿酸血症小鼠尿酸生成和排泄的影响研究[J].中药新药与临床药理,2015,26(5):626-631.
[10]陈光亮,武松,那莎,等.萆薢总皂苷对慢性高尿酸血症大鼠尿酸排泄指标的影响[J].中国中西医结合杂志,2014,34(1):75-80.
[11]朱继孝,曾金祥,罗光明,等.栀子降尿酸有效部位研究[J].中国实验方剂学杂志,2012,18(14):159-161.
[12]曾金祥,魏娟,毕莹,等.车前子醇提物降低急性高尿酸血症小鼠血尿酸水平及机制研究[J].中国实验方剂学杂志,2013,19(9):173-177.
[13]邓建平,林雯.痛风与高尿酸血症患者血清黄嘌呤氧化酶与炎症因子水平比较[J].国际检验医学杂志,2016,37(7):953-954.
[14]刘静,巫斌.炎症因子与高尿酸血症性肾病大鼠的关系及药物干预研究[J].中华临床医师杂志(电子版),2015,9(23):4359-4363.
[15]梁文娟,和劲松,田洋,等.辣木叶提取物降低高尿酸血症小鼠尿酸水平及机理研究[J].安徽农业科学,2017,45(17):108-109.
[16]朱立然,陈光亮.尿酸转运蛋白研究进展[J].中国临床药理学与治疗学,2012,17(11):1289-1294.