自发性高血压大鼠尿液氨基酸代谢谱改变及两色金鸡菊提取物调节作用初探
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摘要
在确证自发性高血压大鼠(SHR)模型成功后比较其与正常大鼠(Wistar)尿液氨基酸代谢谱的差异,在此基础上初步研究两色金鸡菊提取物对SHR血压及氨基酸代谢谱的调节作用。选取经过适应性饲养后的适龄雄性SHR大鼠和同龄Wistar大鼠测量大鼠收缩压(SBP),舒张压(DBP),同时收集大鼠尿液,运用AQC柱前衍生高效液相色谱(HPLC)-荧光法测定尿液中氨基酸代谢谱,利用多元统计分析中的偏最小二乘方判别分析(PLS-DA)研究2组动物的氨基酸代谢差异物。将所有饲养的SHR大鼠随机分成5组,即模型组,两色金鸡菊提取物高、中、低剂量组(3.2,1.6,0.8 g·kg~(-1)),西药卡托普利组(4mg·kg~(-1)),连续灌胃给药4周后收集大鼠尿液,测定各组氨基酸代谢谱。药物干预4周后,与Wistar组相比,SHR组的氨基酸代谢谱中丝氨酸、丙氨酸、酪氨酸、胱氨酸对分组的贡献较大,均显著高于Wistar组;与SHR组相比,卡托普利组的苏氨酸、蛋氨酸较模型组显著降低(P<0.01);新疆两色金鸡菊醇提物低、中、高剂量组氨基酸代谢均有不同程度改变,其中低剂量苏氨酸较模型组显著降低(P<0.01);中剂量组的丝氨酸、苏氨酸较模型组降低(P<0.05),缬氨酸、蛋氨酸、赖氨酸显著降低(P<0.01);大剂量组的苏氨酸、缬氨酸、蛋氨酸、赖氨酸显著降低(P<0.01)。研究结果显示,中、高剂量提取物能明显改善氨基酸代谢异常,帮助进一步阐释两色金鸡菊的药性研究,为高血压病存在氨基酸代谢通路异常提供数据支持。
To compare the amino acid metabolic profiling in urine of spontaneously hypertensive rats( SHR) and normal Wistar rats,and investigate the regulatory effect of extract from Coreopsis tinctoria on blood pressure and amino acid metabolic profiling in SHR. Right aged SHR and Wistar rats were housed to fit the new environment for 2 weeks. After that,their systolic pressure( SBP),diastolic pressure( DBP) were measured and urine was collected. Amino acids profiles for SHR and Wistar rats were acquired by using AQC precolumn derivatization HPLC-fluorescence method,and then partial least squares discriminant analysis( PLS-DA) was applied to facilitate differentiation and determine metabolic differences between collected samples from two groups of rats. Consequently,40 SHR were randomly divided into 5 groups: model group,high,middle,low dosage groups of C. tinctoria extract( 3. 2,1. 6,0. 8 g·kg~(-1)),and captopril group( 4 mg·kg~(-1)). They were treated for 4 weeks by ig administration,and then their urine samples were collected to determine the amino acid metabolic profiling in various groups. After treatment for 4 weeks,as compared with Wistar group,serine,alanine,tyrosine,and cystine in the amino acid metabolic profiling were significantly increased in SHR group. As compared with SHR model group,threonine and methionine were decreased significantly in captopril group( P < 0. 01); amino acid metabolism was changed to different degrees in high,middle,and low dosage groups of C. tinctoria extract,and the threonine in low dose group was significantly decreased( P < 0. 01); serine and threonine were decreased( P < 0. 05),and valine,methionine and lysine were significantly decreased( P < 0. 01) in middle dose group; threonine,valine,methionine and lysine were significantly decreased in large dose group( P < 0. 01). The results showed that middle and high doses of extract from C. tinctoria could significantly improve disturbance of amino acid metabolism,help to further clarify the drug property research of C. tinctoria,and provide data support for amino acid metabolic pathway abnormalities in hypertension patients.
To compare the amino acid metabolic profiling in urine of spontaneously hypertensive rats( SHR) and normal Wistar rats,and investigate the regulatory effect of extract from Coreopsis tinctoria on blood pressure and amino acid metabolic profiling in SHR. Right aged SHR and Wistar rats were housed to fit the new environment for 2 weeks. After that,their systolic pressure( SBP),diastolic pressure( DBP) were measured and urine was collected. Amino acids profiles for SHR and Wistar rats were acquired by using AQC precolumn derivatization HPLC-fluorescence method,and then partial least squares discriminant analysis( PLS-DA) was applied to facilitate differentiation and determine metabolic differences between collected samples from two groups of rats. Consequently,40 SHR were randomly divided into 5 groups: model group,high,middle,low dosage groups of C. tinctoria extract( 3. 2,1. 6,0. 8 g·kg~(-1)),and captopril group( 4 mg·kg~(-1)). They were treated for 4 weeks by ig administration,and then their urine samples were collected to determine the amino acid metabolic profiling in various groups. After treatment for 4 weeks,as compared with Wistar group,serine,alanine,tyrosine,and cystine in the amino acid metabolic profiling were significantly increased in SHR group. As compared with SHR model group,threonine and methionine were decreased significantly in captopril group( P < 0. 01); amino acid metabolism was changed to different degrees in high,middle,and low dosage groups of C. tinctoria extract,and the threonine in low dose group was significantly decreased( P < 0. 01); serine and threonine were decreased( P < 0. 05),and valine,methionine and lysine were significantly decreased( P < 0. 01) in middle dose group; threonine,valine,methionine and lysine were significantly decreased in large dose group( P < 0. 01). The results showed that middle and high doses of extract from C. tinctoria could significantly improve disturbance of amino acid metabolism,help to further clarify the drug property research of C. tinctoria,and provide data support for amino acid metabolic pathway abnormalities in hypertension patients.
引文
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[12]李琳琳,毛新民,张月明,等.新疆地区维吾尔族、哈萨克族2型糖尿病代谢特征与饮食结构分析[J].中华内分泌代谢杂志,2005,21(2):141.
[13]谢自敬,樊勇,李琳琳,等.遗传和环境因素在新疆汉族与维吾尔族2型糖尿病发病中的作用[J].中华内分泌代谢杂志,2008,24(1):13.
[14]卢伟,兰怡,李琳琳,等.两色金鸡菊醇提物对自发性高血压大鼠血压和血浆ET,AngⅡ,CGRP的影响[J].中国实验方剂学杂志,2014,20(5):149.
[2]张雪娟,陈清启,宋力,等.自发性高血压大鼠不同时期肾脏中一氧化氮合酶的变化[J].中国现代医学杂志,2003,13(6):12.
[3]卢伟,马晓丽,兰怡,等.两色金鸡菊醇提物对自发性高血压大鼠尿液的代谢组学研究[J].中国药理学通报,2014,30(9):1311.
[4]张惠源.中国中药资源志要[M].北京:科学出版社,1994.
[5]中国科学院中国植物志编辑委员会.中国植物志.75卷[M].北京:科学出版社,1994.
[6]刘伟新,邓继华,徐鸿.一种金鸡菊花的生药学研究[J].中国民族医药杂志,2009(1):24.
[7]木合布力·阿布力孜,张燕,景兆均,等.新疆昆仑雪菊化学成分的初步定性研究[J].新疆医科大学学报,2010,33(6):628.
[8]Yang Qiang,Sun Yuhua,Zhang Li,et al.Antihypertensive effects of extract from flower buds of Coreopsis tinctoria on spontaneously hypertensive rats[J].Chin Herb Med,2014,6(2):103.
[9]Cao Y,Pang S B,Xu L,et al.Antioxidant activities of Coreopsis tinctoria extracts in vitro[J].Chin J Exp Tradit Medl Form,2011,17:144.
[10]Dmitriev L F,Titov V N.Lipid peroxidation in relation to ageing and the role of endogenous aldehydes in diabetes and other agerelated diseases[J].Ageing Res Rev,2010,9:200.
[11]Frantisek K,Magdalena M,Sona C.Long-term effect of prazosin and losartan administration on blood pressure,heart,carotid artery,and acetylcholine induced dilation of cardiovascular system of young Wistar rats and SHR[J].Gen Physiol Biophys,2013,32:235.
[12]李琳琳,毛新民,张月明,等.新疆地区维吾尔族、哈萨克族2型糖尿病代谢特征与饮食结构分析[J].中华内分泌代谢杂志,2005,21(2):141.
[13]谢自敬,樊勇,李琳琳,等.遗传和环境因素在新疆汉族与维吾尔族2型糖尿病发病中的作用[J].中华内分泌代谢杂志,2008,24(1):13.
[14]卢伟,兰怡,李琳琳,等.两色金鸡菊醇提物对自发性高血压大鼠血压和血浆ET,AngⅡ,CGRP的影响[J].中国实验方剂学杂志,2014,20(5):149.