芒果苷对高尿酸血症小鼠血尿酸及嘌呤代谢相关酶表达的影响
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摘要
目的:研究芒果苷对氧嗪酸钾诱导的高尿酸血症小鼠血尿酸的影响以及对磷酸核糖焦磷酸合成酶(PRPS),磷酸核糖焦磷酸酰胺转移酶(PRPPAT)和次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HGPRT) mRNA表达水平的影响。方法:雄性昆明种小鼠60只,随机分为正常组、高尿酸血症模型组、芒果苷1. 5,3. 0,6. 0 mg·kg~(-1)组、别嘌醇组(1. 0 mg·kg~(-1)),每组10只。按10 m L·kg~(-1)每天灌胃给药2次,连续10次,给药后1 h再灌胃给予氧嗪酸钾(500. 0 mg·kg~(-1))诱导形成高尿酸血症小鼠。磷钨酸法测血清尿酸水平,采用逆转录聚合酶链式反应(RT-PCR)检测小鼠肝脏PRPS,PRPPAT和脑组织中HGPRT mRNA的表达水平。结果:灌胃给予氧嗪酸钾后,与正常组比较,模型组小鼠血尿酸水平显著升高(P <0. 05);给予芒果苷和别嘌醇后,与模型组比较,芒果苷各剂量(1. 5,3. 0,6. 0 mg·kg~(-1))和别嘌醇(1. 0 mg·kg~(-1))均能显著降低高尿酸血症小鼠血清尿酸水平(P <0. 05,P <0. 01);与正常组和模型组比较,芒果苷各剂量组小鼠肝脏PRPS和PRPPAT mRNA的表达没有显著性差异,小鼠脑组织中HGPRT mRNA表达水平也没有显著性差异。结论:在本实验条件下,芒果苷的降尿酸作用与嘌呤代谢相关酶PRPS,PRPPAT和HGPRT mRNA的表达无关。
Objective: To investigate the effect of mangiferin on the mRNA expression of phosphoribosylpyrohoosphate synthetase( PRPS),phosphate ribose pyrophosphate amide transferase( PRPPAT) in liver and hypoxanthine-guanine phosphate transfer enzyme( HGPRT) in brain of hyperuricemic mice induced by potassium oxonate. Method: Hyperuricemic mice were induced through intraperitoneal injection with uricase inhibitor potassium oxonate. The serum uric acid level was determined by the phosphotungstic acid method. The mRNA expression levels of PRPS and PRPPAT in liver as well as HGPRT in brain of hyperuricemic mice were measured by reverse transcriptase polymerase chain reaction( RT-PCR). Result: An intraperitoneal injection with potassium oxonate caused a marked increase in serum uric acid level,compared with normal control group( P <0. 05). Intragastric administration with mangiferin at the doses of 1. 5,3. 0,6. 0 mg·kg~(-1) was able to significantly reduce serum uric acid levels,compared with hyperuricemic control group( P < 0. 05,P < 0. 01); Moreover,the increase in the mRNA expression levels of PRPS and PRPPAT in liver,as well as the decrease in the mRNA expression of HGPRT in brain were observed in hyperuricemic control group,but with no statistically difference.Mangiferin has no impact on the mRNA expressions of PRPS,PRPPAT and HGPRT,compared with hyperuricemic control group. Conclusion: The hyporuricemic effect of mangiferin might not be related with PRPS,PRPPAT and HGPRT in therapeutic dose.
Objective: To investigate the effect of mangiferin on the mRNA expression of phosphoribosylpyrohoosphate synthetase( PRPS),phosphate ribose pyrophosphate amide transferase( PRPPAT) in liver and hypoxanthine-guanine phosphate transfer enzyme( HGPRT) in brain of hyperuricemic mice induced by potassium oxonate. Method: Hyperuricemic mice were induced through intraperitoneal injection with uricase inhibitor potassium oxonate. The serum uric acid level was determined by the phosphotungstic acid method. The mRNA expression levels of PRPS and PRPPAT in liver as well as HGPRT in brain of hyperuricemic mice were measured by reverse transcriptase polymerase chain reaction( RT-PCR). Result: An intraperitoneal injection with potassium oxonate caused a marked increase in serum uric acid level,compared with normal control group( P <0. 05). Intragastric administration with mangiferin at the doses of 1. 5,3. 0,6. 0 mg·kg~(-1) was able to significantly reduce serum uric acid levels,compared with hyperuricemic control group( P < 0. 05,P < 0. 01); Moreover,the increase in the mRNA expression levels of PRPS and PRPPAT in liver,as well as the decrease in the mRNA expression of HGPRT in brain were observed in hyperuricemic control group,but with no statistically difference.Mangiferin has no impact on the mRNA expressions of PRPS,PRPPAT and HGPRT,compared with hyperuricemic control group. Conclusion: The hyporuricemic effect of mangiferin might not be related with PRPS,PRPPAT and HGPRT in therapeutic dose.
引文
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[12]袁丽仙,牛艳芬,高丽辉,等.嘌呤核苷磷酸化酶检测体系优化及芒果苷对其活性的影响[J].中国药理学通报,2012,28(7):966-969.
[13]徐象威,牛艳芬,高丽辉,等.基于肠道尿酸转运体ABCG2的芒果苷降尿酸作用机制[J].中国实验方剂学杂志,2018,24(17):230-234.
[14] Mandal A K,Mount D B. The molecular physiology of uric acid homeostasis[J]. Annu Rev Physiol,2015,77:323-346.
[15]朱明敏,师晓毅,孙维峰.复方土茯苓颗粒对HUA大鼠XO活性及其mRNA的抑制作用[J].中国实验方剂学杂志,2016,22(15):127-130.
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[17] Maiuolo J,Oppedisano F,Gratteri S,et al. Regulation of uric acid metabolism and excretion[J]. Int J Cardiol,2016,213:8-14.
[18] LI H G,HOU P Y,ZHANG X,et al. Hypouricemic effect of allopurinol are improved by pallidifloside D based on the uric acid metabolism enzymes PRPS,HGPRT and PRPPAT[J]. Fitoterapia,2016,113:1-5.
[19] Tabunoki H,Ono H,Ode H,et al. Identification of key uric acid synthesis pathway in a unique mutant silkworm Bombyx mori model of Parkinson's disease[J]. PLo S One,2013,8(7):e69130.
[2] Zoccali C,Mallamaci F. Uric acid,hypertension,and cardiovascular and renal complications[J]. Curr Hypertens Rep,2013,15(6):531-537.
[3]苗志敏.痛风病学[M].北京:人民卫生出版社,2006:25-34.
[4]刘恺,林华,高丽辉,等. 3,5,2',4'-四羟基查尔酮对小鼠尿酸及尿酸合成相关酶基因的影响[J].天然产物研究与开发,2016,28(1):131-135.
[5] Boban M,Kocic G,Radenkovic S,et al. Circulating purine compounds,uric acid,and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease[J]. Ren Fail,2014,36(4):613-618.
[6]姚风艳,孙连娜.芒果苷药理作用及其结构修饰的研究进展[J].中国实验方剂学杂志,2014,20(12):248-252.
[7]杨海光,方莲花,杜冠华.芒果苷的药理作用研究进展[J].中国药理学通报,2016,32(1):5-8.
[8]张幸福,骆桂法,王燕. HPLC同时测定抱茎獐牙菜中獐牙菜苦苷、龙胆苦苷和芒果苷含量[J].中国实验方剂学杂志,2014,20(12):61-64.
[9]孙晨瑜,谢国勇,秦民坚.芒果苷在植物界的分布及药理活性研究进展[J].中国野生植物资源,2017,36(4):39-45.
[10] NIU Y F,LU W,GAO L H,et al. Reducing effect of mangiferin on serum uric acid levels in mice[J].Pharm Biol,2012,50(9):1177-1182.
[11]牛艳芬,高丽辉,刘旭,等.芒果苷对氧嗪酸钾所致慢性高尿酸血症大鼠尿酸及肝肾功能的影响[J].中国药理学通报,2012,28(11):1578-1581.
[12]袁丽仙,牛艳芬,高丽辉,等.嘌呤核苷磷酸化酶检测体系优化及芒果苷对其活性的影响[J].中国药理学通报,2012,28(7):966-969.
[13]徐象威,牛艳芬,高丽辉,等.基于肠道尿酸转运体ABCG2的芒果苷降尿酸作用机制[J].中国实验方剂学杂志,2018,24(17):230-234.
[14] Mandal A K,Mount D B. The molecular physiology of uric acid homeostasis[J]. Annu Rev Physiol,2015,77:323-346.
[15]朱明敏,师晓毅,孙维峰.复方土茯苓颗粒对HUA大鼠XO活性及其mRNA的抑制作用[J].中国实验方剂学杂志,2016,22(15):127-130.
[16] Hsu K C,WANG F S. Fuzzy optimization for detecting enzyme targets of human uric acid metabolism[J].Bioinformatics,2013,29(24):3191-3198.
[17] Maiuolo J,Oppedisano F,Gratteri S,et al. Regulation of uric acid metabolism and excretion[J]. Int J Cardiol,2016,213:8-14.
[18] LI H G,HOU P Y,ZHANG X,et al. Hypouricemic effect of allopurinol are improved by pallidifloside D based on the uric acid metabolism enzymes PRPS,HGPRT and PRPPAT[J]. Fitoterapia,2016,113:1-5.
[19] Tabunoki H,Ono H,Ode H,et al. Identification of key uric acid synthesis pathway in a unique mutant silkworm Bombyx mori model of Parkinson's disease[J]. PLo S One,2013,8(7):e69130.