清热化痰汤治疗青年原发性高血压痰热壅盛证的疗效及代谢组学研究
摘要
目的：观察中药清热化痰汤治疗青年原发性高血压痰热壅盛证的临床疗效。同时基于磁共振氢谱('H-NMR)代谢组学研究方法,结合主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)方法,初步探究青年原发性高血压痰热壅盛证患者血清内源性代谢标志物,观察清热化痰汤对青年原发性高血压痰热壅盛证患者4周末血清内源性代谢标志物的影响。为原发性高血压痰热壅盛证的诊断以及中医药治疗提供客观依据。
方法：选择2010年5月至2012年1月,中国中医科学院广安门医院心内科门诊就诊青年原发性高血压辨证为痰热壅盛证患者33例,采用清热化痰汤治疗4周。治疗期间观察每周患者血压及症状改善情况。从中选取12例男性高血压患者,在治疗前、治疗4周后晨起空腹抽取静脉血,同时随机选取本院体检正常的青年男性志愿者12名晨起空腹抽取静脉血。所有静脉血经低温高速离心机离心后留取血清,保存于-80℃冰箱中。在Bruker AVANCE III-500MHz超导傅立叶变化核磁共振波谱仪上,采用有预饱和的增强谱(NOESY)、弛豫时间编辑(CPMG)和扩散编辑(LED)脉冲序列,将所得积分值行主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA).观察青年原发性高血压痰热壅盛证患者血清内源性代谢产物,以及清热化痰汤干预后患者血清内源性代谢产物的变化。
结果：
1.清热化痰汤对血压的影响：患者血压在服药一周后就有下降,且收缩压与治疗前相比有差异(P<0.05),舒张压与治疗前相比有明显差异(P<0.01)。连续治疗4周后,降压疗效显示：显效23例,占69.69%；有效8例,占24.24%；总有效率为93.93%。无效2例。
2.清热化痰汤对证候及症状的影响：患者服药一周后证候评分即有下降,并与疗前有差异(P<0.05)。连续治疗4周后,证候疗效显示：显效26例,占78.79%；有效5例,占15.14%；总有效率为93.93%。无效2例。且眩晕、头痛、头重如裹、气短、急躁易怒、胸闷、失眠等单一症状均有改善。
3.青年原发性高血压痰热壅盛证患者和健康对照者血清中小分子及大分子化合物可利用代谢组学手段加以区分。得出了青年原发性高血压痰湿壅盛证的特异性血清内源性代谢物为：低密度/极低密度脂蛋白, N-乙酰糖蛋白,0-乙酰糖蛋白,脂类,不饱和脂肪酸,高密度脂蛋白,磷脂酰胆碱,胆碱磷酸,胆碱/磷酸胆碱,丙氨酸,乳酸,谷氨酸盐,葡萄糖,柠檬酸,3-羟基丁酸。
4.青年原发性高血压痰热壅盛证患者服用清热化痰汤治疗4周后血清中小分子及大分子化合物可利用代谢组学手段与治疗前区分。从得分图上看,青年原发性高血压痰热壅盛证治疗后组介于青年原发性高血压痰热壅盛证治疗前组和健康对照组之间,进一步分析发现治疗后患者特异性血清内源性代谢物与治疗前相比有所改善。
结论：
1.临床上应用清热化痰汤治疗青年原发性高血压痰热壅盛证病人疗效显著：降压疗效显示总有效率为93.93%；证候积分疗效显示总有效率为93.93%。证明清热化痰汤可有效降低血压,改善症状。
2.青年原发性高血压痰热壅盛证患者体内存在物质代谢紊乱的情况：糖类代谢紊乱表现在：血清中葡萄糖,乳酸,柠檬酸含量下降。脂类代谢紊乱表现在：血清中低密度/极低密度脂蛋白,脂类,不饱和脂肪酸含量升高；高密度脂蛋白,磷脂酰胆碱,胆碱/磷酸胆碱,胆碱磷酸,3-羟基丁酸含量下降。蛋白质代谢紊乱表现在：血清中丙氨酸,谷氨酸盐含量下降；N-乙酰糖蛋白,0-乙酰糖蛋白含量升高。
3.清热化痰汤可有效改善青年原发性高血压痰热壅盛证患者代谢紊乱的情况,主要表现在：可适当升高血清中葡萄糖、乳酸、柠檬酸、高密度脂蛋白、磷脂酰胆碱、胆碱/磷酸胆碱、胆碱磷酸、3-羟基丁酸、丙氨酸、谷氨酸盐的含量,降低低密度/极低密度脂蛋白、脂类、不饱和脂肪酸、N-乙酰糖蛋白、0-乙酰糖蛋白的含量。
Objective:To observe the curative effect of Chinese medicine Qing Re Hua Tan (QRHT) Tang in youth essential hypertension (YEH) patients with abundant phlegm-heat. And based on'H-NMR metabolomics, combining Principal Components Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA) to explore the serum endogenous biomarker substances of YEH patients with abundant phlegm-heat and observe the effect of QRHT Tang in those serum endogenous biomarker substances after4weeks treatment. Provide objective basis for diagnosis and TCM treatment of EH patients with abundant phlegm-heat syndrome.
Methods:33selected cases all came from Guang'anmen Hospital, China Academy of Chinese Medical Sciences out-patients with YEH patients and differentiated by two associate chief physicians with abundant phlegm-heat syndrome. All the patients were treated by QRHT Tang for4weeks. During the treatment, patient measured his/her blood pressure three times a day and reported it to the doctor when he/she.came to hospital meanwhile the doctor asked the patient about the symptoms and finish the Case Report Form (CRF). Select12male YEH patients and12male healthy young people. All serum samples were detected by'H-NMR and research the differences of metabolites by PCA and PLS-DA.
Results:
1. Curative effect of QRHT Tang on blood pressure:blood pressure began to drop at the very first week. After continuous4weeks'treatment, there were23markedly effective cases and8effective cases; the total effective rate was93.93%.
2. Curative effect of QRHT Tang on syndrome and symptoms:syndrome score began to drop at the very first week. After continuous4weeks'treatment, there were26markedly effective cases and5effective cases; the total effective rate was93.93%. QRHT Tang can improve symptoms.
3. The serum substances of YEH patients with abundant phlegm-heat and the healthy people can be distinguished by'H-NMR metabolomics methods. The serum endogenous biomarker substances of YEII patients with abundant phlegm-heat are:LDL/VLDL, N-Ac, O-Ac, lipid, HDL, PtdCho, Lactate, Alanine, Cho/Pcho, GPC, Glucose,3-HB, Citrate, Glutamine.
4. After4weeks'treatment, the serum substances can be distinguished between the YEH patients with abundant phlegm-heat and the healthy people. The serum endogenous biomarker substances tendered to the healthy people after the treatment.
Conclusion:
1. Chinese medicine QRHT Tang can effectively reduce the patient's blood pressure and the symptoms score, improve the quality of life.
2. There are metabolic disorders in YEH patients with abundant phlegm-heat. The content of Glueose, Lactate and Citrate in those patients are lower than health people shows the carbohydrate metabolism disorders. The content of LDL/VLDL, lipid and UFA in those patients are higher than health people, while the content of HDL, PtdCho, Cho/Pcho, GPC and3-HB in those patients are lower than health people shows the lipid metabolic disorders. The content of Alanine and Glutamine in those patients are lower than health people, while the content of N-Ac and O-Ac in those patients are higher than health people shows the proteometabolism disorders.
3. Chinese medicine QRHT Tang can effectively change the metabolic disorders in YEH patients with abundant phlegm-heat. QRHT tang can appropriately increase the content of Glueose, Lactate, Citrate, HDL, PtdCho, Cho/Pcho, GPC,3-HB, Alanine and Glutamine. It also can appropriately decrease the content of LDL/VLDL, lipid, UFA, N-Ac and O-Ac. Provide objective basis for its curative effect.
方法：选择2010年5月至2012年1月,中国中医科学院广安门医院心内科门诊就诊青年原发性高血压辨证为痰热壅盛证患者33例,采用清热化痰汤治疗4周。治疗期间观察每周患者血压及症状改善情况。从中选取12例男性高血压患者,在治疗前、治疗4周后晨起空腹抽取静脉血,同时随机选取本院体检正常的青年男性志愿者12名晨起空腹抽取静脉血。所有静脉血经低温高速离心机离心后留取血清,保存于-80℃冰箱中。在Bruker AVANCE III-500MHz超导傅立叶变化核磁共振波谱仪上,采用有预饱和的增强谱(NOESY)、弛豫时间编辑(CPMG)和扩散编辑(LED)脉冲序列,将所得积分值行主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA).观察青年原发性高血压痰热壅盛证患者血清内源性代谢产物,以及清热化痰汤干预后患者血清内源性代谢产物的变化。
结果：
1.清热化痰汤对血压的影响：患者血压在服药一周后就有下降,且收缩压与治疗前相比有差异(P<0.05),舒张压与治疗前相比有明显差异(P<0.01)。连续治疗4周后,降压疗效显示：显效23例,占69.69%；有效8例,占24.24%；总有效率为93.93%。无效2例。
2.清热化痰汤对证候及症状的影响：患者服药一周后证候评分即有下降,并与疗前有差异(P<0.05)。连续治疗4周后,证候疗效显示：显效26例,占78.79%；有效5例,占15.14%；总有效率为93.93%。无效2例。且眩晕、头痛、头重如裹、气短、急躁易怒、胸闷、失眠等单一症状均有改善。
3.青年原发性高血压痰热壅盛证患者和健康对照者血清中小分子及大分子化合物可利用代谢组学手段加以区分。得出了青年原发性高血压痰湿壅盛证的特异性血清内源性代谢物为：低密度/极低密度脂蛋白, N-乙酰糖蛋白,0-乙酰糖蛋白,脂类,不饱和脂肪酸,高密度脂蛋白,磷脂酰胆碱,胆碱磷酸,胆碱/磷酸胆碱,丙氨酸,乳酸,谷氨酸盐,葡萄糖,柠檬酸,3-羟基丁酸。
4.青年原发性高血压痰热壅盛证患者服用清热化痰汤治疗4周后血清中小分子及大分子化合物可利用代谢组学手段与治疗前区分。从得分图上看,青年原发性高血压痰热壅盛证治疗后组介于青年原发性高血压痰热壅盛证治疗前组和健康对照组之间,进一步分析发现治疗后患者特异性血清内源性代谢物与治疗前相比有所改善。
结论：
1.临床上应用清热化痰汤治疗青年原发性高血压痰热壅盛证病人疗效显著：降压疗效显示总有效率为93.93%；证候积分疗效显示总有效率为93.93%。证明清热化痰汤可有效降低血压,改善症状。
2.青年原发性高血压痰热壅盛证患者体内存在物质代谢紊乱的情况：糖类代谢紊乱表现在：血清中葡萄糖,乳酸,柠檬酸含量下降。脂类代谢紊乱表现在：血清中低密度/极低密度脂蛋白,脂类,不饱和脂肪酸含量升高；高密度脂蛋白,磷脂酰胆碱,胆碱/磷酸胆碱,胆碱磷酸,3-羟基丁酸含量下降。蛋白质代谢紊乱表现在：血清中丙氨酸,谷氨酸盐含量下降；N-乙酰糖蛋白,0-乙酰糖蛋白含量升高。
3.清热化痰汤可有效改善青年原发性高血压痰热壅盛证患者代谢紊乱的情况,主要表现在：可适当升高血清中葡萄糖、乳酸、柠檬酸、高密度脂蛋白、磷脂酰胆碱、胆碱/磷酸胆碱、胆碱磷酸、3-羟基丁酸、丙氨酸、谷氨酸盐的含量,降低低密度/极低密度脂蛋白、脂类、不饱和脂肪酸、N-乙酰糖蛋白、0-乙酰糖蛋白的含量。
Objective:To observe the curative effect of Chinese medicine Qing Re Hua Tan (QRHT) Tang in youth essential hypertension (YEH) patients with abundant phlegm-heat. And based on'H-NMR metabolomics, combining Principal Components Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA) to explore the serum endogenous biomarker substances of YEH patients with abundant phlegm-heat and observe the effect of QRHT Tang in those serum endogenous biomarker substances after4weeks treatment. Provide objective basis for diagnosis and TCM treatment of EH patients with abundant phlegm-heat syndrome.
Methods:33selected cases all came from Guang'anmen Hospital, China Academy of Chinese Medical Sciences out-patients with YEH patients and differentiated by two associate chief physicians with abundant phlegm-heat syndrome. All the patients were treated by QRHT Tang for4weeks. During the treatment, patient measured his/her blood pressure three times a day and reported it to the doctor when he/she.came to hospital meanwhile the doctor asked the patient about the symptoms and finish the Case Report Form (CRF). Select12male YEH patients and12male healthy young people. All serum samples were detected by'H-NMR and research the differences of metabolites by PCA and PLS-DA.
Results:
1. Curative effect of QRHT Tang on blood pressure:blood pressure began to drop at the very first week. After continuous4weeks'treatment, there were23markedly effective cases and8effective cases; the total effective rate was93.93%.
2. Curative effect of QRHT Tang on syndrome and symptoms:syndrome score began to drop at the very first week. After continuous4weeks'treatment, there were26markedly effective cases and5effective cases; the total effective rate was93.93%. QRHT Tang can improve symptoms.
3. The serum substances of YEH patients with abundant phlegm-heat and the healthy people can be distinguished by'H-NMR metabolomics methods. The serum endogenous biomarker substances of YEII patients with abundant phlegm-heat are:LDL/VLDL, N-Ac, O-Ac, lipid, HDL, PtdCho, Lactate, Alanine, Cho/Pcho, GPC, Glucose,3-HB, Citrate, Glutamine.
4. After4weeks'treatment, the serum substances can be distinguished between the YEH patients with abundant phlegm-heat and the healthy people. The serum endogenous biomarker substances tendered to the healthy people after the treatment.
Conclusion:
1. Chinese medicine QRHT Tang can effectively reduce the patient's blood pressure and the symptoms score, improve the quality of life.
2. There are metabolic disorders in YEH patients with abundant phlegm-heat. The content of Glueose, Lactate and Citrate in those patients are lower than health people shows the carbohydrate metabolism disorders. The content of LDL/VLDL, lipid and UFA in those patients are higher than health people, while the content of HDL, PtdCho, Cho/Pcho, GPC and3-HB in those patients are lower than health people shows the lipid metabolic disorders. The content of Alanine and Glutamine in those patients are lower than health people, while the content of N-Ac and O-Ac in those patients are higher than health people shows the proteometabolism disorders.
3. Chinese medicine QRHT Tang can effectively change the metabolic disorders in YEH patients with abundant phlegm-heat. QRHT tang can appropriately increase the content of Glueose, Lactate, Citrate, HDL, PtdCho, Cho/Pcho, GPC,3-HB, Alanine and Glutamine. It also can appropriately decrease the content of LDL/VLDL, lipid, UFA, N-Ac and O-Ac. Provide objective basis for its curative effect.
引文
[1]清·沈金鳌.杂病源流犀烛.北京：中国中医药出版社,1994.249.
[2]顾健霞,陈健,王健平,等.高血压前期人群合并心血管危险因素及中医证型情况调查[J].中医药临床杂志,2012,(01)：33-35.
[3]衷敬柏.基于医家经验的高血压病中医病名、病因病机与证候研究[J].世界中西医结合杂志,2009,(12)：843-846.
[4]王丽颖,李元,丁毅,等.高血压病中医证候动态研究进展[J].河北中医,2010,(11)：1715-1717.
[5]刘琳琳,范吉平,郭蓉娟,等.高血压病证候要素与白细胞介素6的关系[J].中医杂志,2011,(02)：139-140.
[6]张志辰,张允岭.高血压证候要素与颅内血流变化关系初探[J].中华中医药杂志,2009,(11)：1509-1511.
[7]王嘉麟,郭蓉娟,张允岭,等.高血压病患者证候要素与血脂异常的相关性研究[J].中华中医药杂志,2009,(12)：1574-1577.
[8]刘琳琳,郭蓉娟,张允岭.不同病程高血压病证候要素与白介素-6、高敏C反应蛋白及基质金属蛋白酶9的关系[J].中华中医药杂志,2011,(07)：1583-1586.
[9]彭丽莉,史大卓.原发性高血压病伴抑郁患者的中医证候要素分析[J].北京中医药,2010,(07)：534-536,539.
[10]金香兰,张允岭,陈志刚,等.运用因子分析探讨原发性高血压病证候要素[J].北京中医药大学学报,2011,(02)：131-134,144.
[11]王嘉麟,郭蓉娟,张允岭,等.基于因子分析的高血压病证候要素研究[J].天津中医药,2010,(05)：434-436.
[12]王严冬,刘志龙,杨华伟.珠海地区300名高血压患者中医证型与不同类降压药效果分析[J].甘肃中医,2008,(09)：54-55.
[13]喻怀斌,余希文,吴宁波.高血压脑病中医证型分析[J].实用中医药杂志,2010,(06)：436-437.
[14]李格,史载祥,柳翼.熄风化痰法治疗高血压急性脑出血57例临床观察[J].中医杂志,2002,(06)：433-434,454-455.
[15]向成斌,刘德桓,陈文鑫.高血压性脑卒中758例患者的脉压差与中医证型的分布规律探讨[J].世界中医药,2010,(01)：15-17.
[16]邹志东,范哗,周小棠,等.1996-2005年北京地区高血压病中医证候分析[J].中医杂志,2007,(05)：437-439.
[17]沈翠珍,彭美慈,邝惠容,等.高血压病的中医发病观[J].浙江中医杂 志,2007,(12)：698-700.
[18]刘德峰.从血气上逆论高血压病病机[J].中华现代中西医杂志,2005,3(13)：1226-1227.
[19]李运伦.清热降火为主治疗青壮年高血压病的机理集要.中医药学刊,2003,21(5)：700,710.
[20]徐媛媛,张军平,彭立.浅谈火热内生与高血压病.中国中医基础医学杂志,201016(7)：544,559.
[21]张晓磊,张军平.清热解毒法在原发性高血压病治疗中的应用.吉林中医药,2010,30(1)：22-23.
[22]张焱,何立人.从湿浊内结、土湿侮木辨治高血压病[J].上海中医药杂志,2006,40(6)：17.
[23]董小康.原发性高血压从痰论治近况与用药规律.山东中医杂志,2010,29(11)：806-807.
[24]谈黎.升清降浊汤治疗高血压100例临床疗效观察[J].实用诊断与治疗杂志,2005,19(6)：463.
[25]项成刚,张艳,礼海.中医对原发性高血压病因病机的认识[J].世界中西医结合杂志,2010,(04)：356-357.
[26]彭立,张军平.顽固性高血压从热毒论治[J].山东中医杂志,2008,(01)：3-4.
[27]陈勇,徐丽红.中西医结合治疗肥胖性高血压病40例临床观察[J].江苏中医药,2008,(06)：36-37.
[28]石伟松.温胆汤加减治疗原发性高血压睡眠障碍[J].浙江中西医结合杂志,2004,(08)：35-36.
[29]王丹枫,方祝元.高血压早期肾损害实验室指标与中医辨证分型的相关性[J].北方药学,2011,(03)：58-59.
[30]RedonJ. PascualJM. Development of microalbuminuria inessential hypertension [J]. CurrHypertensRep,2006,8 (2):171-177.
[31]BhmM, ReilJC, DanchinN, eta.1 Association of heart rate with microalbuminuria in cardiovascular risk patients:data from I-SEARCH[J]. Hypertension,2008,26 (1):18-25.
[32]万莉莉,孙洞箫.尿蛋白及尿酶测定在高血压肾损害早期诊断的价值[J].中国保健(医学研究版),2007,15(4)：76-77.
[33]罗承锋,何小琦.星蒌温胆汤治疗高血压病眩晕21例[J].江西中医药,2010,(07)：32-33.
[34]王俅俅,徐京育.黄连温胆汤治疗H型高血压临床观察[J].中西医结合心脑血管病杂志,2012,(02)：147-148.
[35]赵俊华,王新华.旋复竹黄汤治疗痰热型高血压的观察[J].黑龙江中医药,2002,(04)：37-38.
[36]赵学勤.牛黄羚珠丹治疗痰热上壅型二级高血压53例临床观察[J].北京中医,2002,(03)：186.
[37]范联芳.马齿苋治疗痰湿壅阻型高血压.中医杂志,2005,46(6)：414.
[38]元·朱震亨.丹溪心法.上海：上海科学技术出版社,1959,76.
[39]中国高血压防治指南修订委员会.中国高血压防治指南2010.中华高血压杂志,2011,19(8).701-743.
[40]人类年龄划分又有新标准.新闻天地(论文版).2001,(3)：41.
[41]郑筱萸.中药新药临床研究指导原则(试行).中国医药科技出版社,2002：74.
[42]郑筱萸.中药新药临床研究指导原则(试行).中国医药科技出版社,2002：75.
[43]郑筱萸.中药新药临床研究指导原则(试行).中国医药科技出版社,2002：77.
[44]战国·佚名.黄帝内经灵枢.北京：中医古籍出版社.1997,25.
[45]唐·王冰.黄帝内经素问.北京：辽宁科学技术出版社.1997,11,155.
[46]元·朱震亨.丹溪心法.上海：上海科学技术出版社,1959,253.
[47]明·张介宾.景岳全书.北京：人民卫生出版社,1991,393.
[48]元·朱震亨.丹溪心法.上海：上海科学技术出版社,1959,89.
[49]明·龚居中辑著.红炉点雪.上海：上海科技出版社.1982,9：2-4.
[50]清·唐容川.血证论.北京：中国中医药出版社.1996,151.
[51]清·沈金鳌.杂病源流犀烛.北京：中国中医药出版社,1994,249.
[52]汉·张仲景.金匮要略.北京：中医古籍出版社.1997,31.
[53]盛雪梅,张越秋.黄连素治疗原发性高血压病32例临床观察[J].齐齐哈尔医学院学报,2004,(02)：166.
[54]Kang DG, Sohn EJ, Kwon EK, et al. Effects of Berberine on angiotensin-convertingenzyme and NO/cGmp System in vessels. Vascular Pharmacol,2002, 39:281-283.
[55]李倜,迟晓玲.黄连素治疗高血压临床及机理研究概述[J].中医药信息,2003,(04)：12-13.
[56]项平.中药大辞典.上海：上海科学技术出版社,2006,1564.
[57]Hung PH, Lin LC, Wang GJ, el al. Inhibitory effect of evodiamine on aldosterone release by zona glomerulosa cells in male rals. Chin J Physiol, 2001,44(2):53-57.
[58]Deng PY, Ye F, Cai WJ, et al. Stimulation of calcitonin gene-related peptide synthesis and release:mechanisms for a novel antihypertensive drug, rutaecarpine [J]. J Hypertens,2004,22(9):1819-1829.
[59]李岱,罗丹,郭韧,等.降钙素基因相关肽介导吴茱萸次碱的降压作用[J].中南药学,2007,(05)：420-423.
[60]杨晓青,李最琼,曾泗宇,等.吴茱萸次碱对高血压大鼠胸主动脉血管肽酶C表达的影响研究[J].中国药房,2009,(15)：1124-1127.
[61]李宜,胡元会,齐连芬,等.连萸降压胶囊对自发性高血压大鼠血清蛋白质组学分析.中国中医基础医学杂志,2010,16(12)：1121-1122,1131.
[62]卜宪峥,吴华芹,胡元会,等.药对黄连、吴茱萸对高血压大鼠血压和血浆ET、CGRP的影响[J].中西医结合心脑血管病杂志,2011,(09)：1079-1080.
[63]徐宝林,张文娟,孙静芸.桑白皮提取物平喘、利尿作用的研究[J].中成药,2005.09(25)：758-760.
[64]冯冰虹,苏浩冲,杨俊杰.桑白皮非丙酮提取物的药效学研究[J].中药材,2005,(04)：322-326.
[65]项平.中药大辞典.上海：上海科学技术出版社,2006,2786.
[66]Yahara S, Shigeyama C, Nohara T. Structures of anti-ACE and-reninpeptides from Lycii radiciscortex[J].Tetrahedron Lett,1989,30(44): 6041-6042.
[67]王锋,王青.二皮降压饮治疗轻中度高血压80例[J].中国民间疗法,2005,(06)：35-36.
[68]龙世林,陈雅.牡丹皮药理作用及临床研究进展.中国药业,2007,16(3)：63-64.
[69]游淑梅,朱玉婷.夏枯草对自发高血压大鼠血压的影响研究[J].海峡药学,2011,(03)：37-38.
[70]项平.中药大辞典.上海：上海科学技术出版社,2006,2561.
[71]梁健钦,熊万娜,罗远,等.夏枯草提取物对大鼠自发性高血压降血压作用研究[J].中药材,2011,(01)：99-100.
[72]冉懋雄.名贵中药材绿色栽培技术.北京：科学技术文献出版社,2002：12-13.
[73]项平.中药大辞典.上海：上海科学技术出版社,2006,1072.
[74]王瑞娜,唐茜,何凤发.药用白术的药理作用及其综合开发利用.安徽农业科学,2010,38(11)：5610-5611,5627.
[75]项平.中药大辞典.上海：上海科学技术出版社,2006,2065.
[76]郑虎占,董泽宏,佘靖.中药现代研究与应用[M].第4册.北京：学苑出版社,1998,3022.
[77]彭贤,黄舒,郦皆秀,等.泽泻属植物化学成分与药理活性[J].国外医药植物药分册,2000,15(6)：245.
[78]邓刚民,许津.茯苓素：一种潜在的醛固酮拮抗剂团.中国抗生素杂志,1992,17(1)：34-37.
[79]张荣珍,陈志祥,胡素颖,等.3578例高血压中医证型构成临床调查研究[J].中医药临床杂志,2007,(04)：360-364.
[80]王岳屏,严颂琴,彭国顺,等.高血压病病人不同证候与糖脂肪代谢及瘦素水平的关系[J].中西医结合心脑血管病杂志,2007,(06)：476-478.
[81]张建丽,叶德平.高血压病血脂异常与中医辨证分型关系探讨[J].河北中医,2005,(04)：264-265.
[82]刘晓颖,王永霞,陈召起.高血压病血脂ETNO变化与中医辨证分型的关系[J].中医药学刊,2005,(08)：1464-1465.
[83]安芳,张洪飞,林丽娜,等.高血压患者血浆中游离氨基酸的柱前衍生HPLC法测定[J].分析测试学报,2009,(01)：72-75,79.
[84]朱晓伟,高新星,安芳,等.柱前衍生化HPLC-荧光检测法测定高血压患者尿液中22种游离氨基酸的浓度[J].中国药房,2010,(30)：2823-2825.
[85]唐·王冰.黄帝内经素问.北京：辽宁科学技术出版社.1997,40.
[86]常红,徐文刚,杜海燕.清热化痰方对老龄大鼠痰热模型的实验研究[J].广西中医学院学报,2006,(02)：9-11.
[87]明·张介宾.景岳全书.北京：人民卫生出版社,1991,673.
[2]顾健霞,陈健,王健平,等.高血压前期人群合并心血管危险因素及中医证型情况调查[J].中医药临床杂志,2012,(01)：33-35.
[3]衷敬柏.基于医家经验的高血压病中医病名、病因病机与证候研究[J].世界中西医结合杂志,2009,(12)：843-846.
[4]王丽颖,李元,丁毅,等.高血压病中医证候动态研究进展[J].河北中医,2010,(11)：1715-1717.
[5]刘琳琳,范吉平,郭蓉娟,等.高血压病证候要素与白细胞介素6的关系[J].中医杂志,2011,(02)：139-140.
[6]张志辰,张允岭.高血压证候要素与颅内血流变化关系初探[J].中华中医药杂志,2009,(11)：1509-1511.
[7]王嘉麟,郭蓉娟,张允岭,等.高血压病患者证候要素与血脂异常的相关性研究[J].中华中医药杂志,2009,(12)：1574-1577.
[8]刘琳琳,郭蓉娟,张允岭.不同病程高血压病证候要素与白介素-6、高敏C反应蛋白及基质金属蛋白酶9的关系[J].中华中医药杂志,2011,(07)：1583-1586.
[9]彭丽莉,史大卓.原发性高血压病伴抑郁患者的中医证候要素分析[J].北京中医药,2010,(07)：534-536,539.
[10]金香兰,张允岭,陈志刚,等.运用因子分析探讨原发性高血压病证候要素[J].北京中医药大学学报,2011,(02)：131-134,144.
[11]王嘉麟,郭蓉娟,张允岭,等.基于因子分析的高血压病证候要素研究[J].天津中医药,2010,(05)：434-436.
[12]王严冬,刘志龙,杨华伟.珠海地区300名高血压患者中医证型与不同类降压药效果分析[J].甘肃中医,2008,(09)：54-55.
[13]喻怀斌,余希文,吴宁波.高血压脑病中医证型分析[J].实用中医药杂志,2010,(06)：436-437.
[14]李格,史载祥,柳翼.熄风化痰法治疗高血压急性脑出血57例临床观察[J].中医杂志,2002,(06)：433-434,454-455.
[15]向成斌,刘德桓,陈文鑫.高血压性脑卒中758例患者的脉压差与中医证型的分布规律探讨[J].世界中医药,2010,(01)：15-17.
[16]邹志东,范哗,周小棠,等.1996-2005年北京地区高血压病中医证候分析[J].中医杂志,2007,(05)：437-439.
[17]沈翠珍,彭美慈,邝惠容,等.高血压病的中医发病观[J].浙江中医杂 志,2007,(12)：698-700.
[18]刘德峰.从血气上逆论高血压病病机[J].中华现代中西医杂志,2005,3(13)：1226-1227.
[19]李运伦.清热降火为主治疗青壮年高血压病的机理集要.中医药学刊,2003,21(5)：700,710.
[20]徐媛媛,张军平,彭立.浅谈火热内生与高血压病.中国中医基础医学杂志,201016(7)：544,559.
[21]张晓磊,张军平.清热解毒法在原发性高血压病治疗中的应用.吉林中医药,2010,30(1)：22-23.
[22]张焱,何立人.从湿浊内结、土湿侮木辨治高血压病[J].上海中医药杂志,2006,40(6)：17.
[23]董小康.原发性高血压从痰论治近况与用药规律.山东中医杂志,2010,29(11)：806-807.
[24]谈黎.升清降浊汤治疗高血压100例临床疗效观察[J].实用诊断与治疗杂志,2005,19(6)：463.
[25]项成刚,张艳,礼海.中医对原发性高血压病因病机的认识[J].世界中西医结合杂志,2010,(04)：356-357.
[26]彭立,张军平.顽固性高血压从热毒论治[J].山东中医杂志,2008,(01)：3-4.
[27]陈勇,徐丽红.中西医结合治疗肥胖性高血压病40例临床观察[J].江苏中医药,2008,(06)：36-37.
[28]石伟松.温胆汤加减治疗原发性高血压睡眠障碍[J].浙江中西医结合杂志,2004,(08)：35-36.
[29]王丹枫,方祝元.高血压早期肾损害实验室指标与中医辨证分型的相关性[J].北方药学,2011,(03)：58-59.
[30]RedonJ. PascualJM. Development of microalbuminuria inessential hypertension [J]. CurrHypertensRep,2006,8 (2):171-177.
[31]BhmM, ReilJC, DanchinN, eta.1 Association of heart rate with microalbuminuria in cardiovascular risk patients:data from I-SEARCH[J]. Hypertension,2008,26 (1):18-25.
[32]万莉莉,孙洞箫.尿蛋白及尿酶测定在高血压肾损害早期诊断的价值[J].中国保健(医学研究版),2007,15(4)：76-77.
[33]罗承锋,何小琦.星蒌温胆汤治疗高血压病眩晕21例[J].江西中医药,2010,(07)：32-33.
[34]王俅俅,徐京育.黄连温胆汤治疗H型高血压临床观察[J].中西医结合心脑血管病杂志,2012,(02)：147-148.
[35]赵俊华,王新华.旋复竹黄汤治疗痰热型高血压的观察[J].黑龙江中医药,2002,(04)：37-38.
[36]赵学勤.牛黄羚珠丹治疗痰热上壅型二级高血压53例临床观察[J].北京中医,2002,(03)：186.
[37]范联芳.马齿苋治疗痰湿壅阻型高血压.中医杂志,2005,46(6)：414.
[38]元·朱震亨.丹溪心法.上海：上海科学技术出版社,1959,76.
[39]中国高血压防治指南修订委员会.中国高血压防治指南2010.中华高血压杂志,2011,19(8).701-743.
[40]人类年龄划分又有新标准.新闻天地(论文版).2001,(3)：41.
[41]郑筱萸.中药新药临床研究指导原则(试行).中国医药科技出版社,2002：74.
[42]郑筱萸.中药新药临床研究指导原则(试行).中国医药科技出版社,2002：75.
[43]郑筱萸.中药新药临床研究指导原则(试行).中国医药科技出版社,2002：77.
[44]战国·佚名.黄帝内经灵枢.北京：中医古籍出版社.1997,25.
[45]唐·王冰.黄帝内经素问.北京：辽宁科学技术出版社.1997,11,155.
[46]元·朱震亨.丹溪心法.上海：上海科学技术出版社,1959,253.
[47]明·张介宾.景岳全书.北京：人民卫生出版社,1991,393.
[48]元·朱震亨.丹溪心法.上海：上海科学技术出版社,1959,89.
[49]明·龚居中辑著.红炉点雪.上海：上海科技出版社.1982,9：2-4.
[50]清·唐容川.血证论.北京：中国中医药出版社.1996,151.
[51]清·沈金鳌.杂病源流犀烛.北京：中国中医药出版社,1994,249.
[52]汉·张仲景.金匮要略.北京：中医古籍出版社.1997,31.
[53]盛雪梅,张越秋.黄连素治疗原发性高血压病32例临床观察[J].齐齐哈尔医学院学报,2004,(02)：166.
[54]Kang DG, Sohn EJ, Kwon EK, et al. Effects of Berberine on angiotensin-convertingenzyme and NO/cGmp System in vessels. Vascular Pharmacol,2002, 39:281-283.
[55]李倜,迟晓玲.黄连素治疗高血压临床及机理研究概述[J].中医药信息,2003,(04)：12-13.
[56]项平.中药大辞典.上海：上海科学技术出版社,2006,1564.
[57]Hung PH, Lin LC, Wang GJ, el al. Inhibitory effect of evodiamine on aldosterone release by zona glomerulosa cells in male rals. Chin J Physiol, 2001,44(2):53-57.
[58]Deng PY, Ye F, Cai WJ, et al. Stimulation of calcitonin gene-related peptide synthesis and release:mechanisms for a novel antihypertensive drug, rutaecarpine [J]. J Hypertens,2004,22(9):1819-1829.
[59]李岱,罗丹,郭韧,等.降钙素基因相关肽介导吴茱萸次碱的降压作用[J].中南药学,2007,(05)：420-423.
[60]杨晓青,李最琼,曾泗宇,等.吴茱萸次碱对高血压大鼠胸主动脉血管肽酶C表达的影响研究[J].中国药房,2009,(15)：1124-1127.
[61]李宜,胡元会,齐连芬,等.连萸降压胶囊对自发性高血压大鼠血清蛋白质组学分析.中国中医基础医学杂志,2010,16(12)：1121-1122,1131.
[62]卜宪峥,吴华芹,胡元会,等.药对黄连、吴茱萸对高血压大鼠血压和血浆ET、CGRP的影响[J].中西医结合心脑血管病杂志,2011,(09)：1079-1080.
[63]徐宝林,张文娟,孙静芸.桑白皮提取物平喘、利尿作用的研究[J].中成药,2005.09(25)：758-760.
[64]冯冰虹,苏浩冲,杨俊杰.桑白皮非丙酮提取物的药效学研究[J].中药材,2005,(04)：322-326.
[65]项平.中药大辞典.上海：上海科学技术出版社,2006,2786.
[66]Yahara S, Shigeyama C, Nohara T. Structures of anti-ACE and-reninpeptides from Lycii radiciscortex[J].Tetrahedron Lett,1989,30(44): 6041-6042.
[67]王锋,王青.二皮降压饮治疗轻中度高血压80例[J].中国民间疗法,2005,(06)：35-36.
[68]龙世林,陈雅.牡丹皮药理作用及临床研究进展.中国药业,2007,16(3)：63-64.
[69]游淑梅,朱玉婷.夏枯草对自发高血压大鼠血压的影响研究[J].海峡药学,2011,(03)：37-38.
[70]项平.中药大辞典.上海：上海科学技术出版社,2006,2561.
[71]梁健钦,熊万娜,罗远,等.夏枯草提取物对大鼠自发性高血压降血压作用研究[J].中药材,2011,(01)：99-100.
[72]冉懋雄.名贵中药材绿色栽培技术.北京：科学技术文献出版社,2002：12-13.
[73]项平.中药大辞典.上海：上海科学技术出版社,2006,1072.
[74]王瑞娜,唐茜,何凤发.药用白术的药理作用及其综合开发利用.安徽农业科学,2010,38(11)：5610-5611,5627.
[75]项平.中药大辞典.上海：上海科学技术出版社,2006,2065.
[76]郑虎占,董泽宏,佘靖.中药现代研究与应用[M].第4册.北京：学苑出版社,1998,3022.
[77]彭贤,黄舒,郦皆秀,等.泽泻属植物化学成分与药理活性[J].国外医药植物药分册,2000,15(6)：245.
[78]邓刚民,许津.茯苓素：一种潜在的醛固酮拮抗剂团.中国抗生素杂志,1992,17(1)：34-37.
[79]张荣珍,陈志祥,胡素颖,等.3578例高血压中医证型构成临床调查研究[J].中医药临床杂志,2007,(04)：360-364.
[80]王岳屏,严颂琴,彭国顺,等.高血压病病人不同证候与糖脂肪代谢及瘦素水平的关系[J].中西医结合心脑血管病杂志,2007,(06)：476-478.
[81]张建丽,叶德平.高血压病血脂异常与中医辨证分型关系探讨[J].河北中医,2005,(04)：264-265.
[82]刘晓颖,王永霞,陈召起.高血压病血脂ETNO变化与中医辨证分型的关系[J].中医药学刊,2005,(08)：1464-1465.
[83]安芳,张洪飞,林丽娜,等.高血压患者血浆中游离氨基酸的柱前衍生HPLC法测定[J].分析测试学报,2009,(01)：72-75,79.
[84]朱晓伟,高新星,安芳,等.柱前衍生化HPLC-荧光检测法测定高血压患者尿液中22种游离氨基酸的浓度[J].中国药房,2010,(30)：2823-2825.
[85]唐·王冰.黄帝内经素问.北京：辽宁科学技术出版社.1997,40.
[86]常红,徐文刚,杜海燕.清热化痰方对老龄大鼠痰热模型的实验研究[J].广西中医学院学报,2006,(02)：9-11.
[87]明·张介宾.景岳全书.北京：人民卫生出版社,1991,673.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |