乌头碱降解产物化学成分及生物活性研究
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摘要
毛莨科(Ranunculaceae)乌头属(Aconitum L.)植物为多年生、二年生或一年生草本,全世界约有300多种,主要分布于北半球的高海拔地区。我国乌头属植物超过200种,除海南外各省均有分布,我国已有76种乌头属植物被应用于中药处方中,该属植物的根和块茎普遍地应用于治疗多种疾病,例如阳虚汗出,昏厥,风湿热,关节疼痛,肠胃炎,痢疾,水肿,支气管哮喘,肿瘤,以及一些内分泌紊乱引起的疾病如月经不调等。
乌头属植物主要含有生物碱、黄酮和多糖类成分。国内外学者已从乌头属植物中分离鉴定了400多种生物碱类化合物,主要为二萜类生物碱,其中普遍存在且含量较高的是乌头碱、新乌头碱和次乌头碱。研究结果显示,这三种生物碱是乌头属植物中主要的药效成分,具有抗炎、镇痛等活性。同时这三种生物碱也是毒性成分。文献指出这三种双酯型生物碱易发生水解,生成单酯型乌头碱和乌头原碱,单酯型乌头碱仍具有抗炎镇痛活性,但毒性大大降低。
有关单酯型乌头碱活性的报道比较少,为了进一步研究单酯型乌头碱单体的活性,本文对附子中主要的双酯型乌头碱进行了提取、分离和鉴定,得到四个化合物,利用1D NMR、MS和IR等波谱学手段确定了它们的结构。分别为脱氧乌头碱(deoxyaconitine)、次乌头碱(hypaconitine)、乌头碱(aconitine)和新乌头碱(mesaconitine)。
将上述四种双酯型乌头碱水解,共得到11个化合物,利用1D NMR、2D NMR、MS和IR等波谱学手段鉴定了它们的化学结构,其中包括四种单酯型乌头碱分别为苯甲酰乌头碱(benzoylaconine)、苯甲酰新乌头碱(benzoylmesaconine).苯甲酰次乌头碱(benzoylhypaconine)和苯甲酰脱氧乌头碱(benzoyldeoxyaconine);三种乌头原碱分别为乌头原碱(aconine)、新乌头原碱(mesaconine)、次乌头原碱(hypaconine);四种焦乌头碱分别为焦乌头碱(pyroaconitine)、焦新乌头碱(pyromesaconitine)、焦次乌头碱(pyrohypaconitine)和焦脱氧乌头碱(pyrodeoxyaconitine)。另外,本文还对苯甲酰次乌头碱、乌头原碱、新乌头原碱和次乌头原碱、焦乌头碱、焦新乌头碱、焦次乌头碱的1H和13C化学位移进行了全归属,纠正了原有文献对苯甲酰乌头碱和苯甲酰新乌头碱的归属错误。
本论文应用反相高效液相色谱法,使用Agilent Zorbax Eclipse plus-C18 (5μm,250 mm X 4.60 mm),流动相为甲醇(A)和水(包含5mmol/L的醋酸铵和0.2%的乙酸)(B)(A：B=40：60),流速1.0 mL/min,检测波长为235 nm,柱温35℃,对制草乌中新乌头碱,乌头碱,次乌头碱,苯甲酰新乌头碱,苯甲酰乌头碱和苯甲酰次乌头碱进行了含量测定。结果显示：六种化合物进样量在0.01～10.00μg范围内均有良好的线性关系,相关系数r均在0.9995以上(n=8)；有很好的稳定性,测定重复性的RSD值均在1.84-3.17%之间；平均回收率(n=6)在96.83%-104.73%之间,RSD值均小于2.61%,本方法能够准确测定制草乌中的6种生物碱的含量,为草乌类药材的质量控制提供了依据。
本文还建立了一种新的提取生物碱的方法,即基质固相分散法(MSPD),并对MSPD法影响提取率的几个因素如分散剂、洗脱剂、物料比、净化剂、助溶剂和洗脱体积等条件进行了优化。当采用碱性氧化铝为分散剂、样品与分散剂比为1：2、80%的乙腈水溶液(pH=12)作为洗脱剂和洗脱体积为10 mL,由MSPD法提取的新乌头碱、次乌头碱、乌头碱和脱氧乌头碱的提取率分别为2214.44,1769.55,1299.28,275.40μg g-1,各化合物含量的RSD值均小于1.20%,而由回流法得到的四种生物碱的提取率分别为1949.08,1239.75,1152.61,149.03μg g-1,由此可见,MSPD法的提取率较高,且四种生物碱的回收率都在93.16-102.73%之间,回收率良好。此外,MSPD法还具有提取时间短、操作步骤简单、溶剂用量少的优点,因此MSPD法更适合提取提取乌头类药材中生物碱类化合物。
本文还研究了三种单酯型乌头碱对大鼠佐剂性关节炎的作用。结果显示,苯甲酰乌头碱、苯甲酰新乌头碱和苯甲酰次乌头碱均能降低大鼠原发性和继发性足肿胀率,能够明显降低佐剂性关节炎大鼠血沉和白细胞数量,降低MDA含量,升高SOD活性。
Aconitum L. is a large genus of the Ranunculaceae family, which consists of over 300 species distributed all over the world. Most of them grow naturally in high altitudes in the northern hemisphere. The genus Aconitum consist of more than 200 species in China, and is widely distributed in all the provinces of China except Hai nan province. As widely used Chinese herbal medicine,76 Aconitum species in China have been medicinally used. The tubers and roots of Aconitum L (Ranunculaceae) are commonly used for various diseases, such as collapse, syncope, rheumatic fever, painful joints, gastroenteritis, diarrhea, oedema, bronchial asthma, various tumors, and some endocrinal disorders like irregular menstruation.
A literature survey revealed that about 400 alkaloids, some flavonoids and polyglycosides have been isolated and identified from Aconitum L. Mesaconitine, aconitine and hypaconitine are not only toxic, but also analgesic and anti-inflammatory constituents in Aconitum L. The acetyl group at the 8-postion in the diestertype alkaloids is easily hydrolyzed into benzoylmesaconine, benzoylaconine and benzoylhypaconine. Those monoester aconitines showed a much lower toxicity than that of the diester-type aconitines. However, the pharmacological studies showed that they also have significant anti-inflammatory and analgesic actions.
There are few reports about the pharmacological effects of the monoester aconitines. In order to further study the bioactivities of the monoester aconitines, the extraction, separation and determination of active constituents in Radix Aconiti lateralis praeparata were preformed. Four compounds including mesaconitine, aconitine, hypaconitine and deoxyaconitine were separated and identified by]H NMR and 13C NMR.
Eleven compounds were separated from the hydrolysates of the four diester-type alkaloids and identified by 1D NMR,2D NMR, IR and MS. The compounds are benzoyldeoxyaconine, benzoylhypaconine, benzoylaconine, benzoylmesaconine, aconine, mesaconine, hypaconine, pyrodeoxyaconitine, pyrohypaconitine, pyromesaconitine and pyroaconitine. The chemical shift assignment of 1H and 13C were made.
To determine the six alkaloids, including mesaconitine,aconitine, hypaconitine, benzoylmesaconine, benzoylhypaconine and benzoylaconine in Aconitum kusnezoffii Reichb., the chromato graphic separation of the compounds was achieved with an Agilent Zorbax Eclipse plus-C18 column(5μm,250 mm×4.60 mm). The elution was carried out using methanol (A) and water containing 5mmol L-1 ammonium acetate and 0.2% acetic acid (B) (A:B=40:60) as mobile phase at a flow rate of 1.0 mL min-1. UV absorption was measured at 235 nm. The column temperature was maintained at 35℃and the sample injection volume was 5μL.The results revealed that the linearity of the six compounds was in the range of 0.01-10.0μg, with the correlation coefficients from 0.9995 to 0.9999 (n=8). The RSD for determining the six compounds ranged from 1.84% to 3.17%. The stability of the analytes were satisfactory. Mean recoveries ranged from 96.83% to 104.73%, with relative standard deviations less than 2.61%. This method is accurate,reliable and sensitive for determination of six alkaloids in Aconitum kusnezoffii Reichb. and provide a standard for quality control of Aconitum kusnezoffii Reichb..
The matrix solid-phase dispersion (MSPD) was developed for the extraction of four alkaloids, including aconitine, mesaconitine, hypaconitine and deoxyaconitine, from the roots of Aconitum kusnezoffii Reichb.. The effects of several extraction parameters such as dispersion sorbent, ratio of sample to dispersion sorbent, elution solvent, the volume of elution solvent and clean-up sorbent were examined and optimized. When alkaline alumina was used as dispersion sorbent, acetonitrile-water (80:20, v/v pH=12) was used as elution solvent, the ratio of sample to dispersion sorbent was 1:2 and the volume of elution solvent was 10 mL, the extraction yields of mesaconitine, hypaconitine, aconitine and deoxyaconitine obtained by MSPD were 2214.44,1769.55,1299.28 and 275.40μg g-1, respectively. The RSDS of extraction yields for the compounds were all less than 1.20%. Whereas, those obtained by reflux extraction were 1949.08,1239.75,1152.61,149.03μg g-1, respectively. Mean recoveries ranged from 93.16% to 102.73%, with relative standard deviations from 0.27% to 4.17%. Compared with reflux extraction, the MSPD extraction has the advantages in extraction time, and consumption solvent.
This paper also studied the effect of benzoylaconine、benzoylmesaconine and benzoylhypaconine on the adjuvant arthritis profile of rats. The results showed that these alkaloids can inhibited the hind paw edema in rats, decreased erthrocyte sedimentation rate、content of leucocyte and MDA(malon dialdehyde), and increased the activity of SOD(superoxide dismutase).
乌头属植物主要含有生物碱、黄酮和多糖类成分。国内外学者已从乌头属植物中分离鉴定了400多种生物碱类化合物,主要为二萜类生物碱,其中普遍存在且含量较高的是乌头碱、新乌头碱和次乌头碱。研究结果显示,这三种生物碱是乌头属植物中主要的药效成分,具有抗炎、镇痛等活性。同时这三种生物碱也是毒性成分。文献指出这三种双酯型生物碱易发生水解,生成单酯型乌头碱和乌头原碱,单酯型乌头碱仍具有抗炎镇痛活性,但毒性大大降低。
有关单酯型乌头碱活性的报道比较少,为了进一步研究单酯型乌头碱单体的活性,本文对附子中主要的双酯型乌头碱进行了提取、分离和鉴定,得到四个化合物,利用1D NMR、MS和IR等波谱学手段确定了它们的结构。分别为脱氧乌头碱(deoxyaconitine)、次乌头碱(hypaconitine)、乌头碱(aconitine)和新乌头碱(mesaconitine)。
将上述四种双酯型乌头碱水解,共得到11个化合物,利用1D NMR、2D NMR、MS和IR等波谱学手段鉴定了它们的化学结构,其中包括四种单酯型乌头碱分别为苯甲酰乌头碱(benzoylaconine)、苯甲酰新乌头碱(benzoylmesaconine).苯甲酰次乌头碱(benzoylhypaconine)和苯甲酰脱氧乌头碱(benzoyldeoxyaconine);三种乌头原碱分别为乌头原碱(aconine)、新乌头原碱(mesaconine)、次乌头原碱(hypaconine);四种焦乌头碱分别为焦乌头碱(pyroaconitine)、焦新乌头碱(pyromesaconitine)、焦次乌头碱(pyrohypaconitine)和焦脱氧乌头碱(pyrodeoxyaconitine)。另外,本文还对苯甲酰次乌头碱、乌头原碱、新乌头原碱和次乌头原碱、焦乌头碱、焦新乌头碱、焦次乌头碱的1H和13C化学位移进行了全归属,纠正了原有文献对苯甲酰乌头碱和苯甲酰新乌头碱的归属错误。
本论文应用反相高效液相色谱法,使用Agilent Zorbax Eclipse plus-C18 (5μm,250 mm X 4.60 mm),流动相为甲醇(A)和水(包含5mmol/L的醋酸铵和0.2%的乙酸)(B)(A：B=40：60),流速1.0 mL/min,检测波长为235 nm,柱温35℃,对制草乌中新乌头碱,乌头碱,次乌头碱,苯甲酰新乌头碱,苯甲酰乌头碱和苯甲酰次乌头碱进行了含量测定。结果显示：六种化合物进样量在0.01～10.00μg范围内均有良好的线性关系,相关系数r均在0.9995以上(n=8)；有很好的稳定性,测定重复性的RSD值均在1.84-3.17%之间；平均回收率(n=6)在96.83%-104.73%之间,RSD值均小于2.61%,本方法能够准确测定制草乌中的6种生物碱的含量,为草乌类药材的质量控制提供了依据。
本文还建立了一种新的提取生物碱的方法,即基质固相分散法(MSPD),并对MSPD法影响提取率的几个因素如分散剂、洗脱剂、物料比、净化剂、助溶剂和洗脱体积等条件进行了优化。当采用碱性氧化铝为分散剂、样品与分散剂比为1：2、80%的乙腈水溶液(pH=12)作为洗脱剂和洗脱体积为10 mL,由MSPD法提取的新乌头碱、次乌头碱、乌头碱和脱氧乌头碱的提取率分别为2214.44,1769.55,1299.28,275.40μg g-1,各化合物含量的RSD值均小于1.20%,而由回流法得到的四种生物碱的提取率分别为1949.08,1239.75,1152.61,149.03μg g-1,由此可见,MSPD法的提取率较高,且四种生物碱的回收率都在93.16-102.73%之间,回收率良好。此外,MSPD法还具有提取时间短、操作步骤简单、溶剂用量少的优点,因此MSPD法更适合提取提取乌头类药材中生物碱类化合物。
本文还研究了三种单酯型乌头碱对大鼠佐剂性关节炎的作用。结果显示,苯甲酰乌头碱、苯甲酰新乌头碱和苯甲酰次乌头碱均能降低大鼠原发性和继发性足肿胀率,能够明显降低佐剂性关节炎大鼠血沉和白细胞数量,降低MDA含量,升高SOD活性。
Aconitum L. is a large genus of the Ranunculaceae family, which consists of over 300 species distributed all over the world. Most of them grow naturally in high altitudes in the northern hemisphere. The genus Aconitum consist of more than 200 species in China, and is widely distributed in all the provinces of China except Hai nan province. As widely used Chinese herbal medicine,76 Aconitum species in China have been medicinally used. The tubers and roots of Aconitum L (Ranunculaceae) are commonly used for various diseases, such as collapse, syncope, rheumatic fever, painful joints, gastroenteritis, diarrhea, oedema, bronchial asthma, various tumors, and some endocrinal disorders like irregular menstruation.
A literature survey revealed that about 400 alkaloids, some flavonoids and polyglycosides have been isolated and identified from Aconitum L. Mesaconitine, aconitine and hypaconitine are not only toxic, but also analgesic and anti-inflammatory constituents in Aconitum L. The acetyl group at the 8-postion in the diestertype alkaloids is easily hydrolyzed into benzoylmesaconine, benzoylaconine and benzoylhypaconine. Those monoester aconitines showed a much lower toxicity than that of the diester-type aconitines. However, the pharmacological studies showed that they also have significant anti-inflammatory and analgesic actions.
There are few reports about the pharmacological effects of the monoester aconitines. In order to further study the bioactivities of the monoester aconitines, the extraction, separation and determination of active constituents in Radix Aconiti lateralis praeparata were preformed. Four compounds including mesaconitine, aconitine, hypaconitine and deoxyaconitine were separated and identified by]H NMR and 13C NMR.
Eleven compounds were separated from the hydrolysates of the four diester-type alkaloids and identified by 1D NMR,2D NMR, IR and MS. The compounds are benzoyldeoxyaconine, benzoylhypaconine, benzoylaconine, benzoylmesaconine, aconine, mesaconine, hypaconine, pyrodeoxyaconitine, pyrohypaconitine, pyromesaconitine and pyroaconitine. The chemical shift assignment of 1H and 13C were made.
To determine the six alkaloids, including mesaconitine,aconitine, hypaconitine, benzoylmesaconine, benzoylhypaconine and benzoylaconine in Aconitum kusnezoffii Reichb., the chromato graphic separation of the compounds was achieved with an Agilent Zorbax Eclipse plus-C18 column(5μm,250 mm×4.60 mm). The elution was carried out using methanol (A) and water containing 5mmol L-1 ammonium acetate and 0.2% acetic acid (B) (A:B=40:60) as mobile phase at a flow rate of 1.0 mL min-1. UV absorption was measured at 235 nm. The column temperature was maintained at 35℃and the sample injection volume was 5μL.The results revealed that the linearity of the six compounds was in the range of 0.01-10.0μg, with the correlation coefficients from 0.9995 to 0.9999 (n=8). The RSD for determining the six compounds ranged from 1.84% to 3.17%. The stability of the analytes were satisfactory. Mean recoveries ranged from 96.83% to 104.73%, with relative standard deviations less than 2.61%. This method is accurate,reliable and sensitive for determination of six alkaloids in Aconitum kusnezoffii Reichb. and provide a standard for quality control of Aconitum kusnezoffii Reichb..
The matrix solid-phase dispersion (MSPD) was developed for the extraction of four alkaloids, including aconitine, mesaconitine, hypaconitine and deoxyaconitine, from the roots of Aconitum kusnezoffii Reichb.. The effects of several extraction parameters such as dispersion sorbent, ratio of sample to dispersion sorbent, elution solvent, the volume of elution solvent and clean-up sorbent were examined and optimized. When alkaline alumina was used as dispersion sorbent, acetonitrile-water (80:20, v/v pH=12) was used as elution solvent, the ratio of sample to dispersion sorbent was 1:2 and the volume of elution solvent was 10 mL, the extraction yields of mesaconitine, hypaconitine, aconitine and deoxyaconitine obtained by MSPD were 2214.44,1769.55,1299.28 and 275.40μg g-1, respectively. The RSDS of extraction yields for the compounds were all less than 1.20%. Whereas, those obtained by reflux extraction were 1949.08,1239.75,1152.61,149.03μg g-1, respectively. Mean recoveries ranged from 93.16% to 102.73%, with relative standard deviations from 0.27% to 4.17%. Compared with reflux extraction, the MSPD extraction has the advantages in extraction time, and consumption solvent.
This paper also studied the effect of benzoylaconine、benzoylmesaconine and benzoylhypaconine on the adjuvant arthritis profile of rats. The results showed that these alkaloids can inhibited the hind paw edema in rats, decreased erthrocyte sedimentation rate、content of leucocyte and MDA(malon dialdehyde), and increased the activity of SOD(superoxide dismutase).
引文
[1]肖培根,王锋鹏,高峰,等.中国乌头属植物药用亲缘学研究[J].植物分类学报,2006,44(1)：1-46.
[2]中国科学院中国植物志编委会.中国植物志(第27卷)[M].北京：科学出版社,1979：113.
[3]徐航,郑曙光,柴丽.附子治疗阳虚汗出症探讨[J].河南中医,2010,30(10)：1132-1133.
[4]张旭剑.川草乌治疗类风湿性关节炎的应用体会[J].河南中医,1997,17(3)：147.
[5]杨军英,党月兰.松潘乌头总碱的抗炎解热作用[J].中国临床药理学与治疗学,2003,8(4)：441-443.
[6]邓伟,丁明晖.附子汤治疗膝骨关节炎的临床研究[J].中国中医骨伤科杂志,2009,17(10)：23-25.
[7]张黑熊,李岁奎.附子的临床应用四则[J].现代中医药,2003,2：59-60.
[8]杜明.附子治疗内科杂症的体会[J].云南中医中药杂志,2010,31(6)：38-39.
[9]GANG B, YANG Y, QIAN S, et al. Identification of higenamine in Radix Aconiti Lateralis Preparata as a beta2-adrenergic receptor agonist[J]. Acta Pharmacologica Sinica,2008, 29(10):1187-1194
[10]黄永融.乌头抗癌研究概述[J].福建中医药,1991,22(1)：54-56.
[11]WADA K, HAZAWA M, TAKAHASHI K, et al. Inhibitory effects of diterpenoid alkaloids on the growth of A172 human malignant cells[J]. Journal of Natural Products,2007,70(12): 1854-1858.
[12]HAZAWA M, WADA K, TAKAHASHI K, et al. Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth[J]. Investigational New Drugs,2009, 27(2):111-119.
[13]SINGHUBER J, ZHU M, PRINZ S, et al. Aconitum in Traditional Chinese Medicine -A valuable drug or an unpredictable risk? [J]. Journal of Ethnopharmacology,2009,126: 18-30.
[14]傅立国,陈潭清,郎楷永,等.中国高等植物(第3卷)[M].青岛：青岛出版社,2000：404.
[15]BISSET N G. Arrow poisons in China. Part II. Aconitum-botany, chemistry, and pharmacology [J]. Journal of Ethnopharmacology,1981,4:247-336.
[16]杨宜花,丁舸,王江.讨论附子在方剂中的配伍意义[J].四川中医,2008,26(8)：123-124.
[17]符华林.我国乌头属药用植物的研究概况[J].中药材,2004,27(2)：149-152.
[18]唐迎雪.谈乌头类中药的止痛作用及应用[J].陕西中医,1999,20(2)：88-89.
[19]萧崇厚,陆蕴如.中药化学[M].上海：上海科学技术出版社,1987：11.
[20]季字彬.中药复方化学与药理[M].北京：人民卫生出版社,2003：232.
[21]王勇,宋凤瑞,金东明,等.复方中药四逆汤中乌头碱类二萜生物碱的电喷雾串联质谱研究[J].高等学校化学学报,2004,25(1)：85-89.
[22]梁华龙.真武汤及其辩证[J].河南中医,2005,25(10)：4.
[23]王均宁,刘更生.真武汤的药理研究与临床应用[J].中成药,1998,20(11)：45-46.
[24]王宗殿,窦伦平,朱传秀,等.真武汤临床应用举隅[J].中医文选,1995,16(3)：223-224.
[25]中华本草编委会.中华本草(第7卷)[M].上海：上海科学技术出版社,1999(第1版)：101-115.
[26]中国科学院中国植物志编委会.中国植物志(第27卷)[M].北京：科学出版社,1979：270.
[27]国家药典委员会.2010年药典(第一部)[M].北京：化学工业出版社,2010：26.
[28]陈燕,朱元龙,朱任宏.中国乌头的研究Ⅸ.川乌、附子中的生物碱[J].药学学报,1965,12(7)：435-439.
[29]陈泗英,刘玉青,王济承.云南栽培川乌的生物碱成分[J].云南植物研究,1982,4(1)：73-75.
[30]KONNO C, SHIRASAKA M, HIKINO K. Structure of Senbusine A, B and C, diterpenic alkaloids of Aconitum carmichaeli roots from China[J]. Journal of Natural Products,1982. 45(2):128-133.
[31]HIKINO H, SKUROIWA Y, KONNO C. Structure of hokbusine A and B, diterpenic alkaloids of Aconitum carmichaeli roots from Japan[J]. Journal of Natural Products,1983, 46(2):178-182.
[32]KITAGAWA I, YOSHIKAWA I, CHEN Z L, et al. Four new lipo-alkaloids from aconite tuber[J]. Chemical & Pharmaceutical Bulletin,1982,30(2):758-761.
[33]巫碧辉,李玉纯,李小芳,等.乌头、附子等微量元素测定及其强心作用的探讨(第一报)[J].1988,4：19-22.
[34]师海波,周重楚,李延忠,等.川乌总碱的抗炎作用[J].中国中药杂志,1990,15(3)：46-49.
[35]曾瑾,罗霞,江南,等.生川乌水煎液抗肿瘤作用的实验研究[J].四川大学学报(自然科学版),2007,44(6)：1344-1348.
[36]孟庆勇,刘志辉,徐美奕,等.乌头注射液对辐射损伤小鼠胸腺细胞的作用[J].中国辐射卫生,2003,12(3)：139-140.
[37]饶曼人.关于“乌头、附子”强心作用的研究[J].药学学报,1966,13(3)：195-203.
[38]刘天培,潘鑫鑫.中国乌头对血管的作用[J].药学学报,1966,13(4)：250-252.
[39]国家药典委员会.2005年药典(第一部)[M].北京：化学工业出版社,2005：132-133.
[40]王洁之,韩公羽.四川江油附子(Aconitum carmichaeli Debx.)脂溶性生物碱的研究[J]. 药学学报,1985,20(1)：71-73.
[41]陈迪华,梁晓天.中药附子成分研究Ⅰ.去甲猪毛菜碱(salsolin01)的分离及其结构测定[J].药学学报,1982,17(10)：792-794.
[42]洪波.附子化学成分和有效成分的研究[D].长春：吉林农业大学资源与环境学院,2003.
[43]陈海生,韩公羽,刘明珠,等.江油附子中新阿朴啡生物碱附子亭的分离鉴定[J].第二军医大学学报,1992,13(2)：167-168.
[44]张卫东,韩公羽,梁华清.四川江油附子生物碱成分的研究[J].药学学报,1992,27(9)：670-673.
[45]韩公羽,梁华清,张卫东,等.四川江油附子生物碱和新的强心成分研究[J].天然产物研究与开发,1997,9(3)：30-34.
[46]SHIM S H, KIM J S, KANG S S. Norditerpenoid alkaloids from the processed tubers of Aconitum carmichaeli[J]. Chemical & Pharmaceutical Bulletin,2003,51(8):999-1002.
[47]王宪楷,赵同芳,赖盛.中坝鹅掌叶附子中的生物碱研究Ⅰ[J].中国药学杂志,1995,30(12)：716-719.
[48]王宪楷,赵同芳,赖盛.中坝鹅掌叶附子中的生物碱研究Ⅱ[J].中国药学杂志,1996,31(2)：74-77.
[49]陈洪超,王宪楷,赵同芳,等.中坝鹅掌叶附子中的生物碱成分[J].天然产物研究与开发,2003,15(4)：324-340.
[50]徐暾海,赵洪峰,徐雅娟,等.四川江油生附子强心成分的研究[J].中草药,2004,35(9)：964-966.
[51]熊江,古昆,谭宁华.黑顺片的二萜生物碱成分[J].天然产物研究与开发,2008,20(3)：440-465.
[52]张思佳,刘敏卓,刘静涵,等.附子的化学成分研究[J].药学与临床研究,2010,18(3)：262-264.
[53]张风雷,李立纪,刘培儒.药用植物化学与中药有效成分分析研讨会论文集[C].北京：[出版者不详],2008：237-241.
[54]KONNO C, MURAYAMA M, SUGIYAMA K, et al. Isolation and hypoglycemic activity of aconitans A, B, C and D, glycans of Aconitum carmichaeli roots[J]. Planta Medica,1985, 51(2):160-161.
[55]舒晓燕,侯大斌.不同采收期附子多糖含量的比较研究[J].中成药,2008,30(10)：1512-1514.
[56]赵祥升,王惠,许源,等.江油附子多糖含量的测定[J].安徽农业科学,2009,37(2)：650-651.
[57]徐泽民,顾永祚,唐伟华,等.中药川附子痕量砷的测定[J].四川环境,2009,18(4)：39-41.
[58]徐泽民,顾永祚,徐慧,等.示差脉冲阳极溶出伏安法测定中药川附子痕量铅镉[J].四川环境,2000,19(3)：38-39.
[59]卢竞,顾兴平,顾永祚ICP-AES法测定中药川附子中硫、硅和钴[J].成都中医药大学学报,2004,27(4)：53-54.
[60]李保国,李峰.附子中18种无机元素的含量测定[J].中国现代药物应用,2009,3(19)：27-29.
[61]彭书明,苏娟,雷泞菲ICP-AES法测定道地中药材川乌头不同器官和炮制品矿质元素含量[J].安徽农业科学,2009,37(4)：1605-1610.
[62]顾永祚,顾兴平,卢竞.中药川附子中25种化学元素的分析研究[J].四川环境,2004,23(4)：7-11.
[63]顾永祚,徐泽民,寇兴明,等ICP-AES法测定中药川附子微量重金属元素[J].四川环境,1999,18(1)：1-4.
[64]寇兴明,顾永祚,顾兴平.AAS法测定中药川附子微量重金属元素[J].四川环境,1999,18(2)：28-31.
[65]顾兴平,卢竞,顾永祚,等.中药川附子中24种化学元素的分析研究[J].世界元素医学,2004,11(1)：21-26.
[66]曹金红,王涛,张善通.体外循环后的心律失常与镁剂治疗[J].上海医科大学学报,1995,22(4)：288-291.
[67]曹莉,刘新萍,杨萍丽.硫辛酸对老龄大鼠抗衰老作用的研究[J].中国老年学杂志,1995,26(3)：356-358.
[68]SUN W X, LIU S Y, LIU Z Q. et al. A study of aconitum alkaloids from aconite roots in Aconitum carmichaeli Debx using Matrix-assisted Laser Desorption/lonization Mass Spectrometry[J]. Rapid communications in Mass Spectrometry.1998,12(13):821-824.
[69]XIE Y, ZHOU H, WONG Y F, et al. An optimized high-performance liquid chromatography (HPLC) method for benzoylmesaconine determination in Radix Aconiti Lateralis Preparata (Fuzi, aconite roots) and its products[J]. Chinese Medicine,2008,3(1):6-13.
[70]越皓,皮子凤,宋凤瑞,等.生附片化学成分的HPLC/ESI-MS"研究[J].化学学报,2008,66(2)：211-215.
[71]YUE H, PI Z F, SONG F R, et al. Studies on the aconitine-type alkaloids in the roots of Aconitum Carmichaeli Debx. by HPLC/ESIMS/MSn[J]. Talanta,2009,77(5):1800-1807.
[72]顾科民.附子“回阳救逆”作用的初步药理学探讨[J].上海中医药杂志,1962,6：10-19.
[73]周远鹏,刘文化.附子对心血管系统作用和毒性比较[J].中西医结合杂志,1984,4(1)：48-50.
[74]刘树世,刘俊显,王忱元.中药附子强心成分的研究[J].中国地方病学杂志,1985,4(1)：49-52.
[75]左箴,顾科民,杨友才,等.中药附子的研究Ⅴ、附子对“脉微欲绝”病理模型的影响[J].第二军医大学学报,1982,1：19-23.
[76]顾科民,左箴,杨友才,等.中药附子的研究Ⅵ、川附子制剂及提取物“801”对猫心乳头肌的影响[J].第二军医大学学报,1983,4(1)：12-16.
[77]郑可耀,顾科民,关莲芳,等.中药附子的研究Ⅶ、川附子制剂及提取物“801”对麻醉犬心脏血流动力学的影响[J].第二军医大学学报,1982,4：288-297.
[78]周远鹏,范礼理,张丽英.附子药理作用的研究[J].中华医学杂志,1978,58(11)：664-669.
[79]刘文化,周远鹏,曾贵云.去甲乌药碱对实验性心力衰竭的治疗作用[J].药学学报,1988,23(2)：81-85.
[80]FELLER D R, VENKATRAMAN R, MILLER D D. Comparative actions of the trimetoquinol, tetrahydropapaveroline and salsolinol isomers in beta-adrenoceptor systems[J]. Biochemical Pharmacology,1975,24(13-14):1357-1359.
[81]韩公羽,梁华清,廖耀中,等.四川江油附子新的强心成分研究[J].第二军医大学学报,1991,12(1)：10-13.
[82]邓家刚,范丽丽,郝二伟,等.附子的回阳救逆量效关系研究[J].中国实验方剂学杂志,2010,16(9)：150-154.
[83]张明发,沈雅琴.温里药温经止痛除痹的药理研究[J].中国中医药信息杂志,2000,7(1)：29-32.
[84]邓家刚,范丽丽,杨柯,等.附子镇痛作用量效关系的实验研究[J].中华中医药学刊,2009,27(11)：2249-2251.
[85]徐红萌,姜慧卿.附子对神经病理性疼痛大鼠的镇痛作用[J].中华麻醉学杂志,2005,25(5)：381-384.
[86]王铁东,刘皎,曲雷鸣.附子对神经病理性疼痛大鼠的影响[J].中华中医药学刊,2010,28(5)：1083-1085.
[87]LIOU S S, LIU I M, LAI M C, et al. Comparison of the antinociceptive action of crude Fuzei, the root of Aconitum, and its processed products[J]. Journal of Ethnopharmacology, 2005,99(3):379-383.
[88]杨煜荣,耿慕筠,张福全,等.附子的消炎作用及其与肾上腺皮质的关系[J].药学学报,1966,13(8)：573-576.
[89]李德兴,王幼林,高长忠.中国乌头及附子对垂体-肾上腺皮质系统作用的研究[J].药学学报,1966,13(2)：101-105.
[90]张家俊,陈文为.去甲乌药碱对关节液的保护作用.[J].药学学报,1985,20(6)：423-426.
[91]HIKONO H, KONNO C, TAKATA H, et al. Antiinflammatory principles of Aconitum roots[J]. Journal of Pharmacobio-dynamics,1980,3(10):514-525.
[92]金治萃,田德真,杨煜荣,等.附子注射液对免疫影响的初步研究[J].内蒙古医学杂志,1982,2(2)：357-359.
[93]陈玉春.人参、附子与参附汤的免疫调节作用机理初探[J].中成药,1994,16(8)：30-31.
[94]苗智慧,刘京生,王燕凌,等.附子酸性多糖提高免疫低下小鼠免疫功能的实验研究[J].河北中医,2007,29(12)：1130-1132.
[95]马健,樊巧玲,牧野充弘,等.阳虚模型小鼠腹腔巨噬细胞Ⅰa抗原表达及乌头碱的作用[J].中国中西医结合杂志,1995,15(9)：544-546.
[96]董兰凤,刘京生,苗智慧,等.附子多糖对H22和S180荷瘤小鼠的抗肿瘤作用研究[J].中国中医基础医学杂志,2003,9(9)：14-17.
[97]任丽娅,曾升平.附子提取物对移植性肝癌H-22细胞凋亡影响的实验研究[J].河南中医,2008,28(11)：34-37.
[98]GAO T T, BI H T, MA S, et al. The antitumor and immunostimulating activities of water soluble polysaccharides from Radix Aconiti, Radix Aconiti Lateralis and Radix Aconiti Kusnezoffii[J]. Natural Product Communications,2010,5(3):447-455.
[99]饶朝龙,彭成.乌头类生物碱对ras基因表达影响及其抗肿瘤分子机制研究[J].现代预防医学,2010,37(6)：1098-1103.
[100]张涛,王桂杰,白书阁,等.附子对老年大鼠抗氧化系统影响的实验研究[J].中国老年学杂志,2001,21(2)：135-136.
[101]周远鹏,刘文化.附子水溶部分对内毒素休克的治疗作用[J].中药通报,1988,13(5)：43-45.
[102]扬帆,林树新,张福琴,等.四川江油附子提取物抗失血性休克的作用研究[J].第四军医大学学报,1996,17(2)：116.
[103]郭尹玲,扈晓宇,钟森,等.附子对免疫性肝损伤模型大鼠的影响及代谢组学研究[J].西部医学,2010,22(5)：797-799.
[104]高娜,杨勇,王世军,等.HPLC测定附子对大鼠肝组织中腺苷酸含量及能荷的影响[J].中国实验方剂学杂志,2010,16(15)：172-175.
[105]邵陆,周远鹏.附子水溶部分对心律失常的影响[J].中药通报,1988,13(6)：42-44.
[106]张宝恒,袁绍华,王彤,等.去甲乌药碱对实验性过缓型心律失常的治疗作用[J].生理科学,1983,3(1)：53-54.
[107]高天礼,庄宏.附子Ⅰ对抗小鼠实验性缓慢型心律失常的作用[J].中医杂志,1980,(10)：71-72.
[108]刘兰兰,王友群.附子对腺嘌呤造成的小鼠慢性肾衰的疗效及其机制探讨[J].亚太传统医药,2010,6(6)：28-30.
[109]于乐,吴伟康.附子多糖对胰岛素抵抗脂肪细胞模型葡萄糖摄取的影响[J].亚太传统医 药,2009,5(7)：11-13.
[110]李劲平,吴伟康,曾英,等.附子总生物碱对缺血心肌蛋白质组的影响[J].中南药学,2008,6(1)：18-21.
[111]张团笑,牛彩琴,秦晓民.附子水煎剂对家兔离体肺动脉血管的舒张作用[J].中草药,2005,27(6)：694-697.
[112]牛彩琴,张团笑,徐厚谦,等.附子水煎剂对家兔离体主动脉血管舒张作用的研究[J].中药药理与临床,2004,20(4)：23-25.
[113]王永高,朱元龙,朱任宏.中国乌头的研究ⅩⅢ.北草乌中的生物碱[J].药学学报,1980,15(9)：526-531.
[114]李正邦,吕光华,陈东林,等.草乌中生物碱的化学研究[J].天然产物研究与开发,1997,9(1)：9-14.
[115]WANG F P, LI Z B, CHE C T. Beiwudine, a Norditerpenoid Alkaloid from Aconitum kusnezoffii[J]. Journal of Natural Products,1998,61(12):1555-1556.
[116]ZINUROVA E G, KHAKIMOVA T V, SPIRIKHIN L V, et al. A new norditerpenoid alkaloid acsonine from the roots of Aconitum kusnezoffii Reichb. [J]. Russian Chemical Bulletin,2001,50(2):311-312.
[117]赵英永,戴云,崔秀明,等.草乌中挥发油化学成分的研究[J].中成药,2007,29(4)：588-590.
[118]孙玉军,陈彦,吴佳静,等.草乌多糖的分离纯化和组成性质研究[J].中国药学杂志,2000,35(11)：731-733.
[119]GAO T T, BIA H T, MA S, et al. Structure elucidation and antioxidant activity of a novel a-(1→3),(1→4)-d-glucan from Aconitum kusnezoffii Reichb. [J]. International Journal of Biological Macromolecules,2010,46(1):85-90.
[120]许庆轩,王勇,刘志强,等.草乌中二萜类生物碱的电喷雾串联质谱研究[J].高等学校化学学报,2005,26(4)：638-641.
[121]刘世芳,杨毓章.北乌头总生物碱及乌头碱对几种药物引起的心电图变化的影响[J].药学学报,1980,15(9)：520-525.
[122]黄园,侯世祥,谢瑞犀,等.草乌抗肝癌靶向制剂有效部位的浸出、纯化与确证[J].中国中药杂志,1997,22(11)：667-703.
[123]程薇,赵淑英,牛欣.草乌提取物外用对大鼠足跖肿胀影响的实验研究[J].中华中医药杂志,2008,增刊：100-101.
[124]刘安平,于智芬.草乌对离体蟾蜍坐骨神经动作电位的影响[J].时珍国医国药,2008,19(5)：1009-1110.
[125]陈桂余,罗爱梅,张自优,等.草乌甲素注射液对蛙离体坐骨神经干动作电位的影响[J].现代医药卫生,2010,26(16)：2405-2406.
[126]WENG W Y, XU H N, LI H, et al. Skin permeability and anti-inflammatory analgesic activities of bulleyaconitine A liposomes[J]. Chinese Journal of Clinical Pharmacy,2003, 12(3):131-135.
[127]WONG S K, TSAI S K, KWAN S Y. Analysis of proprietary Chinese medicines for the presence of toxic ingredients by LC/MS/MS[J]. Journals of Pharmaceutical and Biomedical Analysis,2002,30(1):161-170.
[128]宋东江,陆满文,李汉青.乌头碱类化合物毒理学研究概况[J].中国药理学通报,1989,5(5)：272-273.
[129]BENN M H, JACYNO J M. The toxicology and pharmacology of diterpenoid alkaloids[J]. Alkaloids:Chemical and Biological Perspectives,1983, (1):153-210.
[130]CHAN T Y K. Incidence of herb-induced aconitine poisoning[J]. Drug Safety,2002,25, 823-828.
[131]SMITH S W, Shah R R, Hunt J L, et al. Bidirectional ventricular tachycardia resulting from herbal aconite poisoning[J]. Annals of emergency medicine,2005,45(1):100-101.
[132]SHEIKH-ZADE Y R, CHEREDNIK I L, GALENKO-YAROSHEVSKII P A. Peculiarities of cardiotropic effect of aconitine[J]. Bulletin of experimental biology and medicine,2000, 129(4):365-366.
[133]ONUR R., BOZDAGI O, AYATA C. Effects of aconitine on neurotransmitter release in the rat neuromuscular junction[J]. Neuropharmacology,1995.34(9):1139-1145.
[134]康永.中药药理学[M].北京：科学出版社,2001：90-93.
[135]卢中秋,胡国新.乌头碱急性中毒及诊治研究现状[J].中国中西医结合急救杂志,2005,12(2)：119-121.
[136]WADA K, NIHIR M. HAYAKAWA H, et al. Effects of long-term administrations of aconitine on electrocardiogram and tissue concentrations of aconitine and its metabolites in mice[J]. Forensic Science International,2005.148:21-29.
[137]TAKI M, NIITU K, OMIYA, Y, et al.8-O-cinnamoylneoline, a new alkaloid from the flower buds of Aconitum carmichaeli and its toxic and analgesic activities. Planta Medica 69: 800-803.
[138]MIZUGAKI M, SUZUKI Y. Aconite poisoning[J]. Japanese Journal of Toxicity,1989,2: 225-228.
[139]MORI T, BANDO H, KAN AIWA Y. et al. Studies on the constituents of Aconitum species. Ⅱ.structrue of deoxyjesaconitine[J]. Chemitry Pharmacology Bulletin,1983.31(8): 2884-2886.
[140]越皓,皮子凤,赵宇峰,等.电喷雾串联质谱分析附子炮制中的化学成分变化[J].分析化学,2007,35(7)：959-963.
[141]图雅,张贵军,刘志强,等.传统蒙药草乌炮制原理的电喷雾质谱研究[J].分析化学,2008,31(2)：204-206.
[142]黄勤安,张聿梅,何轶,等.乌头碱水解转化规律的研究[J].中国中药杂志,2007,32(20)：2143-2145.
[143]刘永刚,于达亮,陈玉娟,等HPLC-ESI-MSn法研究中乌头碱在水中的化学反应[J].中国新药杂志,2008,17(2)：351-354.
[144]郗瑞云,刘永刚,张宏桂,等HPLC-MSn法研究次乌头碱在水中的化学反应[J].北京中医药大学学报,2008,30(8)：539-542.
[145]越皓,许庆轩,才永新,等.pH对双酯型生物碱水解影响规律的电喷雾串联质谱研究[J].分析测试学报,2005,24(增刊)：3-4.
[146]XIE Y, JIANG Z H, ZHOU H, et al. Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by high-performance liquid chromatography[J]. Journal of Chromatography A,2005,1093(1-2):195-203.
[147]JAMPANI B H, ALFRED K. Isolation and identification of four norditerpenoid alkaloids from processed and unprocessed roots tubers of Aconitum Ferox[J]. Journal of Nature Products,1993,56(6):801-809.
[148]ISHIMI K, MAKINO M, ASADA Y, et al. Norditerpenoid alkaloids from Aconitum manshuricum[J]. Journal of Nature Medicine,2006,60:255-257.
[149]黄建明,郭济贤,孙明明.草乌中生物碱含量测定方法研究[J].中药材,2002,25(12)：878-880.
[150]何军,祝林,奉建芳.附子总生物碱含量测定方法比较[J].现代中药研究与实践,2003,17(6)：20-22.
[151]邓江,龙丽娜,杜方麓.市售乌头炮制品中的乌头总碱、酯型生物碱、乌头碱的乌头碱的含量检查[J].中成药,2007,29(12)：14-15.
[152]李云霞,孙照,郭艳玲.酸性染料比色法测定川乌、草乌中总乌头生物碱的含量[J].中成药,2000,22(9)：662-663.
[153]杜倩,潘金火,严国俊.复方川乌止痛贴剂中酯型生物碱及总生物碱的含量测定[J].时珍国医国药,2008,19(1)：158-160.
[154]薛燕,陈世智.乌头炮制品酯型生物碱含量的红外光谱定量分析法[J].中医药学刊,2005,23(6)：987-988.
[155]楚春莲,王萍.生品、制品草乌毒性成分变化分析[J].齐齐哈尔大学学报,2004,25(5)：546.
[156]杨秀兰,文正洪.黄草乌质量标准研究[J].中国民族民间医药杂志,2005,(72)：54-57.
[157]武凤兰,洪星,苏德森.乌头碱-PVC膜电击的制备与应用[J].沈阳药学院学报,1988,5(3)：199-203.
[158]王玉华,王伟,刘笑融.交流示波极普滴定法测定草乌中总乌头生物碱的含量[J].中草药,1992,23(10)：521.
[159]庞志功,汪宝琪,沈万香.薄层-萤光法测定雪山一枝蒿中乌头碱的含量[J].中国中药杂志,1991,16(8)：485.
[160]WANG Z H, WEN J, XING J B, et al. Quantitative determination of diterpenoid alkaloids in four species of Aconitum by HPLC[J]. Journal of Pharmaceutical and Biomedical Analysis, 2006,40(4),1031-1034.
[161]粟贵,廖林川,颜有仪,等HPLC同时测定生物样品中新乌头碱、乌头碱、次乌头碱的含量[J].中国药学杂志,2009,44(12)：946-950.
[162]孙兰,周海燕,赵润怀,等HPLC法同时测定附子中6种单酯和双酯型生物碱[J].中草药,2009,40(1)：131-134.
[163]FENG H T, SAM F Y L. Determination of five toxic alkaloids in two common herbal medicines with capillary electrophoresis[J]. Journal of Chromatography A,2002,973(1-2), 243-247.
[164]孙爱民,陈德华,毕培曦.高效毛细管电泳法测定中草药川乌、草乌中乌头碱的含量[J].色谱,1999,17(1)：67-69.
[165]HU X L, CUI S Y, LIU J Q. Field-Amplified sample stacking for rapid and sensitive determination of aconitine alkaloids by CE using an ionic liquid electrolyte system[J]. Chromatographia,2010,72(9-10),993-997.
[166]OHTA H, SETO Y, TSUNODA N, et al. Determination of Aconitum alkaloids in blood and urine samples Ⅱ. Capillary liquid chromatographic-frit fast atom bombardment mass spectrometric analysis[J]. Journal of Chromatography B,1998,714(2):215-221.
[167]刘秀秀,晁若冰.反相离子对色谱法测定附子中生物碱成分[J].药学学报,2006,41(4)：365-369.
[168]ITO K, OHYAMA Y, HISHINUMA T, et al. Determination of Aconitum alkaloids in the tubers of Aconitum japonicum using gas chromatography/selected ion monitoring. Planta Medica,1996.62:57-59.
[169]BEYER J, FRANK T P. KRAEMER T, et al. Detection and validated quantification of toxic alkaloids in human blood plasma-comparison of LC-APCI-MS with LC-ESI-MS/MS[J]. Journal of Mass Spectrometry,2007,42(5),621-633.
[170]WU W, LIANG Z T, ZHAO Z Z, et al. Direct analysis of alkaloid profiling in plant tissue by using matrix-assisted laser desorption/ionization mass spectrometry[J]. Journal of Mass Spectrometry,2007,42(1),58-69.
[171]KANEKO R, HATTORI S, FURUTA S, et al. Sensitive analysis of aconitine, hypaconitine, mesaconitine and jesaconitine in human body fluids and Aconitum tubers by LC/ESI-TOF-MS[J]. Journal of Mass Spectrometry,2006,41(6),810-814.
[172]ZHANG F TANG M H. CHEN A L J. et al. Simultaneous quantitation of aconitine, mesaconitine. hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine in human plasma by liquid chromatography-tandem mass spectrometry and pharmacokinetics evaluation of "SHEN-FU" injectable powder[J]. Journal of Chromatography B,2008, 873(2),173-179.
[173]STEVEN A B. Matrix solid-phase dispersion[J]. Journal of Chromatography A,2000,885, 115-127.
[174]STEVEN A B. Matrix solid-phase dispersion[J]. Journal of biochemical and biophysical method,2007,70,151-162.
[175]MARTHA P G D L, MARI L R R. A validated matrix solid-phase dispersion method for the extraction of organophosphorus pesticides from bovine samples[J]. Food Chemistry,2009, 114:1510-1516.
[176]ANA C M, DORA M T, CRISTINA T D C. Application of sample disruption methods in the extraction of anthocyanins from solid or semi-solid vegetable samples[J]. Journal of Chromatography A,2006,1129:14-20.
[177]LI J, DONG F S, LIU X Get al. Determination of Pentachloronitrobenzene and Its Metabolites in Ginseng by Matrix Solid-Phase Dispersion and GC-MS-MS[J]. Chromatographia,2009,69(9/10):1113-1117.
[178]MARIA F A, MARIA L, J.PABLO L, et al. Development of a matrix solid-phase dispersion method for the simultaneous determination of pyrethroid and organochlorinated pesticides in cattle feed[J]. Journal of Chromatography A,2009,1216:2832-2842.
[179]SARA B, ANTONIO D C. Matrix solid-phase dispersion as a valuable tool for extracting contaminants from foodstuffs[J]. Journal of biochemical and biophysical methods,2007,70: 163-179.
[180]STEVEN A B. Matrix solid-phase dispersion[J]. Journal of biochemical and biophysical method,2007,70,151-162.
[181]王华燕,胡文祥,刘接卿等.药物治疗类风湿关节炎的研究近况[J].中国医药导报,2007,9(3)：237-239.
[182]VAISAR T, PENNATHUR S, GREEN S, et al. Shotgun proteomics implicates protease inhibition and complement activation in the antlinflarnmatory properties of HDL[J]. J Chin Invest,2007,117(3):746-756.
[183]赵水平.高密度脂蛋白的研究现状[J].中国动脉硬化杂志,2005,13(6)：673-675.
[184]冯芳,丁志建,刘俊.佐剂性关节炎大鼠模型的实验研究[J].天津药学,2004,16(2)：1-4.
[185]徐淑云,卞如濂,陈修.药理实验方法学[M].北京：人民卫生出版社,1991,723-725.
[2]中国科学院中国植物志编委会.中国植物志(第27卷)[M].北京：科学出版社,1979：113.
[3]徐航,郑曙光,柴丽.附子治疗阳虚汗出症探讨[J].河南中医,2010,30(10)：1132-1133.
[4]张旭剑.川草乌治疗类风湿性关节炎的应用体会[J].河南中医,1997,17(3)：147.
[5]杨军英,党月兰.松潘乌头总碱的抗炎解热作用[J].中国临床药理学与治疗学,2003,8(4)：441-443.
[6]邓伟,丁明晖.附子汤治疗膝骨关节炎的临床研究[J].中国中医骨伤科杂志,2009,17(10)：23-25.
[7]张黑熊,李岁奎.附子的临床应用四则[J].现代中医药,2003,2：59-60.
[8]杜明.附子治疗内科杂症的体会[J].云南中医中药杂志,2010,31(6)：38-39.
[9]GANG B, YANG Y, QIAN S, et al. Identification of higenamine in Radix Aconiti Lateralis Preparata as a beta2-adrenergic receptor agonist[J]. Acta Pharmacologica Sinica,2008, 29(10):1187-1194
[10]黄永融.乌头抗癌研究概述[J].福建中医药,1991,22(1)：54-56.
[11]WADA K, HAZAWA M, TAKAHASHI K, et al. Inhibitory effects of diterpenoid alkaloids on the growth of A172 human malignant cells[J]. Journal of Natural Products,2007,70(12): 1854-1858.
[12]HAZAWA M, WADA K, TAKAHASHI K, et al. Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth[J]. Investigational New Drugs,2009, 27(2):111-119.
[13]SINGHUBER J, ZHU M, PRINZ S, et al. Aconitum in Traditional Chinese Medicine -A valuable drug or an unpredictable risk? [J]. Journal of Ethnopharmacology,2009,126: 18-30.
[14]傅立国,陈潭清,郎楷永,等.中国高等植物(第3卷)[M].青岛：青岛出版社,2000：404.
[15]BISSET N G. Arrow poisons in China. Part II. Aconitum-botany, chemistry, and pharmacology [J]. Journal of Ethnopharmacology,1981,4:247-336.
[16]杨宜花,丁舸,王江.讨论附子在方剂中的配伍意义[J].四川中医,2008,26(8)：123-124.
[17]符华林.我国乌头属药用植物的研究概况[J].中药材,2004,27(2)：149-152.
[18]唐迎雪.谈乌头类中药的止痛作用及应用[J].陕西中医,1999,20(2)：88-89.
[19]萧崇厚,陆蕴如.中药化学[M].上海：上海科学技术出版社,1987：11.
[20]季字彬.中药复方化学与药理[M].北京：人民卫生出版社,2003：232.
[21]王勇,宋凤瑞,金东明,等.复方中药四逆汤中乌头碱类二萜生物碱的电喷雾串联质谱研究[J].高等学校化学学报,2004,25(1)：85-89.
[22]梁华龙.真武汤及其辩证[J].河南中医,2005,25(10)：4.
[23]王均宁,刘更生.真武汤的药理研究与临床应用[J].中成药,1998,20(11)：45-46.
[24]王宗殿,窦伦平,朱传秀,等.真武汤临床应用举隅[J].中医文选,1995,16(3)：223-224.
[25]中华本草编委会.中华本草(第7卷)[M].上海：上海科学技术出版社,1999(第1版)：101-115.
[26]中国科学院中国植物志编委会.中国植物志(第27卷)[M].北京：科学出版社,1979：270.
[27]国家药典委员会.2010年药典(第一部)[M].北京：化学工业出版社,2010：26.
[28]陈燕,朱元龙,朱任宏.中国乌头的研究Ⅸ.川乌、附子中的生物碱[J].药学学报,1965,12(7)：435-439.
[29]陈泗英,刘玉青,王济承.云南栽培川乌的生物碱成分[J].云南植物研究,1982,4(1)：73-75.
[30]KONNO C, SHIRASAKA M, HIKINO K. Structure of Senbusine A, B and C, diterpenic alkaloids of Aconitum carmichaeli roots from China[J]. Journal of Natural Products,1982. 45(2):128-133.
[31]HIKINO H, SKUROIWA Y, KONNO C. Structure of hokbusine A and B, diterpenic alkaloids of Aconitum carmichaeli roots from Japan[J]. Journal of Natural Products,1983, 46(2):178-182.
[32]KITAGAWA I, YOSHIKAWA I, CHEN Z L, et al. Four new lipo-alkaloids from aconite tuber[J]. Chemical & Pharmaceutical Bulletin,1982,30(2):758-761.
[33]巫碧辉,李玉纯,李小芳,等.乌头、附子等微量元素测定及其强心作用的探讨(第一报)[J].1988,4：19-22.
[34]师海波,周重楚,李延忠,等.川乌总碱的抗炎作用[J].中国中药杂志,1990,15(3)：46-49.
[35]曾瑾,罗霞,江南,等.生川乌水煎液抗肿瘤作用的实验研究[J].四川大学学报(自然科学版),2007,44(6)：1344-1348.
[36]孟庆勇,刘志辉,徐美奕,等.乌头注射液对辐射损伤小鼠胸腺细胞的作用[J].中国辐射卫生,2003,12(3)：139-140.
[37]饶曼人.关于“乌头、附子”强心作用的研究[J].药学学报,1966,13(3)：195-203.
[38]刘天培,潘鑫鑫.中国乌头对血管的作用[J].药学学报,1966,13(4)：250-252.
[39]国家药典委员会.2005年药典(第一部)[M].北京：化学工业出版社,2005：132-133.
[40]王洁之,韩公羽.四川江油附子(Aconitum carmichaeli Debx.)脂溶性生物碱的研究[J]. 药学学报,1985,20(1)：71-73.
[41]陈迪华,梁晓天.中药附子成分研究Ⅰ.去甲猪毛菜碱(salsolin01)的分离及其结构测定[J].药学学报,1982,17(10)：792-794.
[42]洪波.附子化学成分和有效成分的研究[D].长春：吉林农业大学资源与环境学院,2003.
[43]陈海生,韩公羽,刘明珠,等.江油附子中新阿朴啡生物碱附子亭的分离鉴定[J].第二军医大学学报,1992,13(2)：167-168.
[44]张卫东,韩公羽,梁华清.四川江油附子生物碱成分的研究[J].药学学报,1992,27(9)：670-673.
[45]韩公羽,梁华清,张卫东,等.四川江油附子生物碱和新的强心成分研究[J].天然产物研究与开发,1997,9(3)：30-34.
[46]SHIM S H, KIM J S, KANG S S. Norditerpenoid alkaloids from the processed tubers of Aconitum carmichaeli[J]. Chemical & Pharmaceutical Bulletin,2003,51(8):999-1002.
[47]王宪楷,赵同芳,赖盛.中坝鹅掌叶附子中的生物碱研究Ⅰ[J].中国药学杂志,1995,30(12)：716-719.
[48]王宪楷,赵同芳,赖盛.中坝鹅掌叶附子中的生物碱研究Ⅱ[J].中国药学杂志,1996,31(2)：74-77.
[49]陈洪超,王宪楷,赵同芳,等.中坝鹅掌叶附子中的生物碱成分[J].天然产物研究与开发,2003,15(4)：324-340.
[50]徐暾海,赵洪峰,徐雅娟,等.四川江油生附子强心成分的研究[J].中草药,2004,35(9)：964-966.
[51]熊江,古昆,谭宁华.黑顺片的二萜生物碱成分[J].天然产物研究与开发,2008,20(3)：440-465.
[52]张思佳,刘敏卓,刘静涵,等.附子的化学成分研究[J].药学与临床研究,2010,18(3)：262-264.
[53]张风雷,李立纪,刘培儒.药用植物化学与中药有效成分分析研讨会论文集[C].北京：[出版者不详],2008：237-241.
[54]KONNO C, MURAYAMA M, SUGIYAMA K, et al. Isolation and hypoglycemic activity of aconitans A, B, C and D, glycans of Aconitum carmichaeli roots[J]. Planta Medica,1985, 51(2):160-161.
[55]舒晓燕,侯大斌.不同采收期附子多糖含量的比较研究[J].中成药,2008,30(10)：1512-1514.
[56]赵祥升,王惠,许源,等.江油附子多糖含量的测定[J].安徽农业科学,2009,37(2)：650-651.
[57]徐泽民,顾永祚,唐伟华,等.中药川附子痕量砷的测定[J].四川环境,2009,18(4)：39-41.
[58]徐泽民,顾永祚,徐慧,等.示差脉冲阳极溶出伏安法测定中药川附子痕量铅镉[J].四川环境,2000,19(3)：38-39.
[59]卢竞,顾兴平,顾永祚ICP-AES法测定中药川附子中硫、硅和钴[J].成都中医药大学学报,2004,27(4)：53-54.
[60]李保国,李峰.附子中18种无机元素的含量测定[J].中国现代药物应用,2009,3(19)：27-29.
[61]彭书明,苏娟,雷泞菲ICP-AES法测定道地中药材川乌头不同器官和炮制品矿质元素含量[J].安徽农业科学,2009,37(4)：1605-1610.
[62]顾永祚,顾兴平,卢竞.中药川附子中25种化学元素的分析研究[J].四川环境,2004,23(4)：7-11.
[63]顾永祚,徐泽民,寇兴明,等ICP-AES法测定中药川附子微量重金属元素[J].四川环境,1999,18(1)：1-4.
[64]寇兴明,顾永祚,顾兴平.AAS法测定中药川附子微量重金属元素[J].四川环境,1999,18(2)：28-31.
[65]顾兴平,卢竞,顾永祚,等.中药川附子中24种化学元素的分析研究[J].世界元素医学,2004,11(1)：21-26.
[66]曹金红,王涛,张善通.体外循环后的心律失常与镁剂治疗[J].上海医科大学学报,1995,22(4)：288-291.
[67]曹莉,刘新萍,杨萍丽.硫辛酸对老龄大鼠抗衰老作用的研究[J].中国老年学杂志,1995,26(3)：356-358.
[68]SUN W X, LIU S Y, LIU Z Q. et al. A study of aconitum alkaloids from aconite roots in Aconitum carmichaeli Debx using Matrix-assisted Laser Desorption/lonization Mass Spectrometry[J]. Rapid communications in Mass Spectrometry.1998,12(13):821-824.
[69]XIE Y, ZHOU H, WONG Y F, et al. An optimized high-performance liquid chromatography (HPLC) method for benzoylmesaconine determination in Radix Aconiti Lateralis Preparata (Fuzi, aconite roots) and its products[J]. Chinese Medicine,2008,3(1):6-13.
[70]越皓,皮子凤,宋凤瑞,等.生附片化学成分的HPLC/ESI-MS"研究[J].化学学报,2008,66(2)：211-215.
[71]YUE H, PI Z F, SONG F R, et al. Studies on the aconitine-type alkaloids in the roots of Aconitum Carmichaeli Debx. by HPLC/ESIMS/MSn[J]. Talanta,2009,77(5):1800-1807.
[72]顾科民.附子“回阳救逆”作用的初步药理学探讨[J].上海中医药杂志,1962,6：10-19.
[73]周远鹏,刘文化.附子对心血管系统作用和毒性比较[J].中西医结合杂志,1984,4(1)：48-50.
[74]刘树世,刘俊显,王忱元.中药附子强心成分的研究[J].中国地方病学杂志,1985,4(1)：49-52.
[75]左箴,顾科民,杨友才,等.中药附子的研究Ⅴ、附子对“脉微欲绝”病理模型的影响[J].第二军医大学学报,1982,1：19-23.
[76]顾科民,左箴,杨友才,等.中药附子的研究Ⅵ、川附子制剂及提取物“801”对猫心乳头肌的影响[J].第二军医大学学报,1983,4(1)：12-16.
[77]郑可耀,顾科民,关莲芳,等.中药附子的研究Ⅶ、川附子制剂及提取物“801”对麻醉犬心脏血流动力学的影响[J].第二军医大学学报,1982,4：288-297.
[78]周远鹏,范礼理,张丽英.附子药理作用的研究[J].中华医学杂志,1978,58(11)：664-669.
[79]刘文化,周远鹏,曾贵云.去甲乌药碱对实验性心力衰竭的治疗作用[J].药学学报,1988,23(2)：81-85.
[80]FELLER D R, VENKATRAMAN R, MILLER D D. Comparative actions of the trimetoquinol, tetrahydropapaveroline and salsolinol isomers in beta-adrenoceptor systems[J]. Biochemical Pharmacology,1975,24(13-14):1357-1359.
[81]韩公羽,梁华清,廖耀中,等.四川江油附子新的强心成分研究[J].第二军医大学学报,1991,12(1)：10-13.
[82]邓家刚,范丽丽,郝二伟,等.附子的回阳救逆量效关系研究[J].中国实验方剂学杂志,2010,16(9)：150-154.
[83]张明发,沈雅琴.温里药温经止痛除痹的药理研究[J].中国中医药信息杂志,2000,7(1)：29-32.
[84]邓家刚,范丽丽,杨柯,等.附子镇痛作用量效关系的实验研究[J].中华中医药学刊,2009,27(11)：2249-2251.
[85]徐红萌,姜慧卿.附子对神经病理性疼痛大鼠的镇痛作用[J].中华麻醉学杂志,2005,25(5)：381-384.
[86]王铁东,刘皎,曲雷鸣.附子对神经病理性疼痛大鼠的影响[J].中华中医药学刊,2010,28(5)：1083-1085.
[87]LIOU S S, LIU I M, LAI M C, et al. Comparison of the antinociceptive action of crude Fuzei, the root of Aconitum, and its processed products[J]. Journal of Ethnopharmacology, 2005,99(3):379-383.
[88]杨煜荣,耿慕筠,张福全,等.附子的消炎作用及其与肾上腺皮质的关系[J].药学学报,1966,13(8)：573-576.
[89]李德兴,王幼林,高长忠.中国乌头及附子对垂体-肾上腺皮质系统作用的研究[J].药学学报,1966,13(2)：101-105.
[90]张家俊,陈文为.去甲乌药碱对关节液的保护作用.[J].药学学报,1985,20(6)：423-426.
[91]HIKONO H, KONNO C, TAKATA H, et al. Antiinflammatory principles of Aconitum roots[J]. Journal of Pharmacobio-dynamics,1980,3(10):514-525.
[92]金治萃,田德真,杨煜荣,等.附子注射液对免疫影响的初步研究[J].内蒙古医学杂志,1982,2(2)：357-359.
[93]陈玉春.人参、附子与参附汤的免疫调节作用机理初探[J].中成药,1994,16(8)：30-31.
[94]苗智慧,刘京生,王燕凌,等.附子酸性多糖提高免疫低下小鼠免疫功能的实验研究[J].河北中医,2007,29(12)：1130-1132.
[95]马健,樊巧玲,牧野充弘,等.阳虚模型小鼠腹腔巨噬细胞Ⅰa抗原表达及乌头碱的作用[J].中国中西医结合杂志,1995,15(9)：544-546.
[96]董兰凤,刘京生,苗智慧,等.附子多糖对H22和S180荷瘤小鼠的抗肿瘤作用研究[J].中国中医基础医学杂志,2003,9(9)：14-17.
[97]任丽娅,曾升平.附子提取物对移植性肝癌H-22细胞凋亡影响的实验研究[J].河南中医,2008,28(11)：34-37.
[98]GAO T T, BI H T, MA S, et al. The antitumor and immunostimulating activities of water soluble polysaccharides from Radix Aconiti, Radix Aconiti Lateralis and Radix Aconiti Kusnezoffii[J]. Natural Product Communications,2010,5(3):447-455.
[99]饶朝龙,彭成.乌头类生物碱对ras基因表达影响及其抗肿瘤分子机制研究[J].现代预防医学,2010,37(6)：1098-1103.
[100]张涛,王桂杰,白书阁,等.附子对老年大鼠抗氧化系统影响的实验研究[J].中国老年学杂志,2001,21(2)：135-136.
[101]周远鹏,刘文化.附子水溶部分对内毒素休克的治疗作用[J].中药通报,1988,13(5)：43-45.
[102]扬帆,林树新,张福琴,等.四川江油附子提取物抗失血性休克的作用研究[J].第四军医大学学报,1996,17(2)：116.
[103]郭尹玲,扈晓宇,钟森,等.附子对免疫性肝损伤模型大鼠的影响及代谢组学研究[J].西部医学,2010,22(5)：797-799.
[104]高娜,杨勇,王世军,等.HPLC测定附子对大鼠肝组织中腺苷酸含量及能荷的影响[J].中国实验方剂学杂志,2010,16(15)：172-175.
[105]邵陆,周远鹏.附子水溶部分对心律失常的影响[J].中药通报,1988,13(6)：42-44.
[106]张宝恒,袁绍华,王彤,等.去甲乌药碱对实验性过缓型心律失常的治疗作用[J].生理科学,1983,3(1)：53-54.
[107]高天礼,庄宏.附子Ⅰ对抗小鼠实验性缓慢型心律失常的作用[J].中医杂志,1980,(10)：71-72.
[108]刘兰兰,王友群.附子对腺嘌呤造成的小鼠慢性肾衰的疗效及其机制探讨[J].亚太传统医药,2010,6(6)：28-30.
[109]于乐,吴伟康.附子多糖对胰岛素抵抗脂肪细胞模型葡萄糖摄取的影响[J].亚太传统医 药,2009,5(7)：11-13.
[110]李劲平,吴伟康,曾英,等.附子总生物碱对缺血心肌蛋白质组的影响[J].中南药学,2008,6(1)：18-21.
[111]张团笑,牛彩琴,秦晓民.附子水煎剂对家兔离体肺动脉血管的舒张作用[J].中草药,2005,27(6)：694-697.
[112]牛彩琴,张团笑,徐厚谦,等.附子水煎剂对家兔离体主动脉血管舒张作用的研究[J].中药药理与临床,2004,20(4)：23-25.
[113]王永高,朱元龙,朱任宏.中国乌头的研究ⅩⅢ.北草乌中的生物碱[J].药学学报,1980,15(9)：526-531.
[114]李正邦,吕光华,陈东林,等.草乌中生物碱的化学研究[J].天然产物研究与开发,1997,9(1)：9-14.
[115]WANG F P, LI Z B, CHE C T. Beiwudine, a Norditerpenoid Alkaloid from Aconitum kusnezoffii[J]. Journal of Natural Products,1998,61(12):1555-1556.
[116]ZINUROVA E G, KHAKIMOVA T V, SPIRIKHIN L V, et al. A new norditerpenoid alkaloid acsonine from the roots of Aconitum kusnezoffii Reichb. [J]. Russian Chemical Bulletin,2001,50(2):311-312.
[117]赵英永,戴云,崔秀明,等.草乌中挥发油化学成分的研究[J].中成药,2007,29(4)：588-590.
[118]孙玉军,陈彦,吴佳静,等.草乌多糖的分离纯化和组成性质研究[J].中国药学杂志,2000,35(11)：731-733.
[119]GAO T T, BIA H T, MA S, et al. Structure elucidation and antioxidant activity of a novel a-(1→3),(1→4)-d-glucan from Aconitum kusnezoffii Reichb. [J]. International Journal of Biological Macromolecules,2010,46(1):85-90.
[120]许庆轩,王勇,刘志强,等.草乌中二萜类生物碱的电喷雾串联质谱研究[J].高等学校化学学报,2005,26(4)：638-641.
[121]刘世芳,杨毓章.北乌头总生物碱及乌头碱对几种药物引起的心电图变化的影响[J].药学学报,1980,15(9)：520-525.
[122]黄园,侯世祥,谢瑞犀,等.草乌抗肝癌靶向制剂有效部位的浸出、纯化与确证[J].中国中药杂志,1997,22(11)：667-703.
[123]程薇,赵淑英,牛欣.草乌提取物外用对大鼠足跖肿胀影响的实验研究[J].中华中医药杂志,2008,增刊：100-101.
[124]刘安平,于智芬.草乌对离体蟾蜍坐骨神经动作电位的影响[J].时珍国医国药,2008,19(5)：1009-1110.
[125]陈桂余,罗爱梅,张自优,等.草乌甲素注射液对蛙离体坐骨神经干动作电位的影响[J].现代医药卫生,2010,26(16)：2405-2406.
[126]WENG W Y, XU H N, LI H, et al. Skin permeability and anti-inflammatory analgesic activities of bulleyaconitine A liposomes[J]. Chinese Journal of Clinical Pharmacy,2003, 12(3):131-135.
[127]WONG S K, TSAI S K, KWAN S Y. Analysis of proprietary Chinese medicines for the presence of toxic ingredients by LC/MS/MS[J]. Journals of Pharmaceutical and Biomedical Analysis,2002,30(1):161-170.
[128]宋东江,陆满文,李汉青.乌头碱类化合物毒理学研究概况[J].中国药理学通报,1989,5(5)：272-273.
[129]BENN M H, JACYNO J M. The toxicology and pharmacology of diterpenoid alkaloids[J]. Alkaloids:Chemical and Biological Perspectives,1983, (1):153-210.
[130]CHAN T Y K. Incidence of herb-induced aconitine poisoning[J]. Drug Safety,2002,25, 823-828.
[131]SMITH S W, Shah R R, Hunt J L, et al. Bidirectional ventricular tachycardia resulting from herbal aconite poisoning[J]. Annals of emergency medicine,2005,45(1):100-101.
[132]SHEIKH-ZADE Y R, CHEREDNIK I L, GALENKO-YAROSHEVSKII P A. Peculiarities of cardiotropic effect of aconitine[J]. Bulletin of experimental biology and medicine,2000, 129(4):365-366.
[133]ONUR R., BOZDAGI O, AYATA C. Effects of aconitine on neurotransmitter release in the rat neuromuscular junction[J]. Neuropharmacology,1995.34(9):1139-1145.
[134]康永.中药药理学[M].北京：科学出版社,2001：90-93.
[135]卢中秋,胡国新.乌头碱急性中毒及诊治研究现状[J].中国中西医结合急救杂志,2005,12(2)：119-121.
[136]WADA K, NIHIR M. HAYAKAWA H, et al. Effects of long-term administrations of aconitine on electrocardiogram and tissue concentrations of aconitine and its metabolites in mice[J]. Forensic Science International,2005.148:21-29.
[137]TAKI M, NIITU K, OMIYA, Y, et al.8-O-cinnamoylneoline, a new alkaloid from the flower buds of Aconitum carmichaeli and its toxic and analgesic activities. Planta Medica 69: 800-803.
[138]MIZUGAKI M, SUZUKI Y. Aconite poisoning[J]. Japanese Journal of Toxicity,1989,2: 225-228.
[139]MORI T, BANDO H, KAN AIWA Y. et al. Studies on the constituents of Aconitum species. Ⅱ.structrue of deoxyjesaconitine[J]. Chemitry Pharmacology Bulletin,1983.31(8): 2884-2886.
[140]越皓,皮子凤,赵宇峰,等.电喷雾串联质谱分析附子炮制中的化学成分变化[J].分析化学,2007,35(7)：959-963.
[141]图雅,张贵军,刘志强,等.传统蒙药草乌炮制原理的电喷雾质谱研究[J].分析化学,2008,31(2)：204-206.
[142]黄勤安,张聿梅,何轶,等.乌头碱水解转化规律的研究[J].中国中药杂志,2007,32(20)：2143-2145.
[143]刘永刚,于达亮,陈玉娟,等HPLC-ESI-MSn法研究中乌头碱在水中的化学反应[J].中国新药杂志,2008,17(2)：351-354.
[144]郗瑞云,刘永刚,张宏桂,等HPLC-MSn法研究次乌头碱在水中的化学反应[J].北京中医药大学学报,2008,30(8)：539-542.
[145]越皓,许庆轩,才永新,等.pH对双酯型生物碱水解影响规律的电喷雾串联质谱研究[J].分析测试学报,2005,24(增刊)：3-4.
[146]XIE Y, JIANG Z H, ZHOU H, et al. Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by high-performance liquid chromatography[J]. Journal of Chromatography A,2005,1093(1-2):195-203.
[147]JAMPANI B H, ALFRED K. Isolation and identification of four norditerpenoid alkaloids from processed and unprocessed roots tubers of Aconitum Ferox[J]. Journal of Nature Products,1993,56(6):801-809.
[148]ISHIMI K, MAKINO M, ASADA Y, et al. Norditerpenoid alkaloids from Aconitum manshuricum[J]. Journal of Nature Medicine,2006,60:255-257.
[149]黄建明,郭济贤,孙明明.草乌中生物碱含量测定方法研究[J].中药材,2002,25(12)：878-880.
[150]何军,祝林,奉建芳.附子总生物碱含量测定方法比较[J].现代中药研究与实践,2003,17(6)：20-22.
[151]邓江,龙丽娜,杜方麓.市售乌头炮制品中的乌头总碱、酯型生物碱、乌头碱的乌头碱的含量检查[J].中成药,2007,29(12)：14-15.
[152]李云霞,孙照,郭艳玲.酸性染料比色法测定川乌、草乌中总乌头生物碱的含量[J].中成药,2000,22(9)：662-663.
[153]杜倩,潘金火,严国俊.复方川乌止痛贴剂中酯型生物碱及总生物碱的含量测定[J].时珍国医国药,2008,19(1)：158-160.
[154]薛燕,陈世智.乌头炮制品酯型生物碱含量的红外光谱定量分析法[J].中医药学刊,2005,23(6)：987-988.
[155]楚春莲,王萍.生品、制品草乌毒性成分变化分析[J].齐齐哈尔大学学报,2004,25(5)：546.
[156]杨秀兰,文正洪.黄草乌质量标准研究[J].中国民族民间医药杂志,2005,(72)：54-57.
[157]武凤兰,洪星,苏德森.乌头碱-PVC膜电击的制备与应用[J].沈阳药学院学报,1988,5(3)：199-203.
[158]王玉华,王伟,刘笑融.交流示波极普滴定法测定草乌中总乌头生物碱的含量[J].中草药,1992,23(10)：521.
[159]庞志功,汪宝琪,沈万香.薄层-萤光法测定雪山一枝蒿中乌头碱的含量[J].中国中药杂志,1991,16(8)：485.
[160]WANG Z H, WEN J, XING J B, et al. Quantitative determination of diterpenoid alkaloids in four species of Aconitum by HPLC[J]. Journal of Pharmaceutical and Biomedical Analysis, 2006,40(4),1031-1034.
[161]粟贵,廖林川,颜有仪,等HPLC同时测定生物样品中新乌头碱、乌头碱、次乌头碱的含量[J].中国药学杂志,2009,44(12)：946-950.
[162]孙兰,周海燕,赵润怀,等HPLC法同时测定附子中6种单酯和双酯型生物碱[J].中草药,2009,40(1)：131-134.
[163]FENG H T, SAM F Y L. Determination of five toxic alkaloids in two common herbal medicines with capillary electrophoresis[J]. Journal of Chromatography A,2002,973(1-2), 243-247.
[164]孙爱民,陈德华,毕培曦.高效毛细管电泳法测定中草药川乌、草乌中乌头碱的含量[J].色谱,1999,17(1)：67-69.
[165]HU X L, CUI S Y, LIU J Q. Field-Amplified sample stacking for rapid and sensitive determination of aconitine alkaloids by CE using an ionic liquid electrolyte system[J]. Chromatographia,2010,72(9-10),993-997.
[166]OHTA H, SETO Y, TSUNODA N, et al. Determination of Aconitum alkaloids in blood and urine samples Ⅱ. Capillary liquid chromatographic-frit fast atom bombardment mass spectrometric analysis[J]. Journal of Chromatography B,1998,714(2):215-221.
[167]刘秀秀,晁若冰.反相离子对色谱法测定附子中生物碱成分[J].药学学报,2006,41(4)：365-369.
[168]ITO K, OHYAMA Y, HISHINUMA T, et al. Determination of Aconitum alkaloids in the tubers of Aconitum japonicum using gas chromatography/selected ion monitoring. Planta Medica,1996.62:57-59.
[169]BEYER J, FRANK T P. KRAEMER T, et al. Detection and validated quantification of toxic alkaloids in human blood plasma-comparison of LC-APCI-MS with LC-ESI-MS/MS[J]. Journal of Mass Spectrometry,2007,42(5),621-633.
[170]WU W, LIANG Z T, ZHAO Z Z, et al. Direct analysis of alkaloid profiling in plant tissue by using matrix-assisted laser desorption/ionization mass spectrometry[J]. Journal of Mass Spectrometry,2007,42(1),58-69.
[171]KANEKO R, HATTORI S, FURUTA S, et al. Sensitive analysis of aconitine, hypaconitine, mesaconitine and jesaconitine in human body fluids and Aconitum tubers by LC/ESI-TOF-MS[J]. Journal of Mass Spectrometry,2006,41(6),810-814.
[172]ZHANG F TANG M H. CHEN A L J. et al. Simultaneous quantitation of aconitine, mesaconitine. hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine in human plasma by liquid chromatography-tandem mass spectrometry and pharmacokinetics evaluation of "SHEN-FU" injectable powder[J]. Journal of Chromatography B,2008, 873(2),173-179.
[173]STEVEN A B. Matrix solid-phase dispersion[J]. Journal of Chromatography A,2000,885, 115-127.
[174]STEVEN A B. Matrix solid-phase dispersion[J]. Journal of biochemical and biophysical method,2007,70,151-162.
[175]MARTHA P G D L, MARI L R R. A validated matrix solid-phase dispersion method for the extraction of organophosphorus pesticides from bovine samples[J]. Food Chemistry,2009, 114:1510-1516.
[176]ANA C M, DORA M T, CRISTINA T D C. Application of sample disruption methods in the extraction of anthocyanins from solid or semi-solid vegetable samples[J]. Journal of Chromatography A,2006,1129:14-20.
[177]LI J, DONG F S, LIU X Get al. Determination of Pentachloronitrobenzene and Its Metabolites in Ginseng by Matrix Solid-Phase Dispersion and GC-MS-MS[J]. Chromatographia,2009,69(9/10):1113-1117.
[178]MARIA F A, MARIA L, J.PABLO L, et al. Development of a matrix solid-phase dispersion method for the simultaneous determination of pyrethroid and organochlorinated pesticides in cattle feed[J]. Journal of Chromatography A,2009,1216:2832-2842.
[179]SARA B, ANTONIO D C. Matrix solid-phase dispersion as a valuable tool for extracting contaminants from foodstuffs[J]. Journal of biochemical and biophysical methods,2007,70: 163-179.
[180]STEVEN A B. Matrix solid-phase dispersion[J]. Journal of biochemical and biophysical method,2007,70,151-162.
[181]王华燕,胡文祥,刘接卿等.药物治疗类风湿关节炎的研究近况[J].中国医药导报,2007,9(3)：237-239.
[182]VAISAR T, PENNATHUR S, GREEN S, et al. Shotgun proteomics implicates protease inhibition and complement activation in the antlinflarnmatory properties of HDL[J]. J Chin Invest,2007,117(3):746-756.
[183]赵水平.高密度脂蛋白的研究现状[J].中国动脉硬化杂志,2005,13(6)：673-675.
[184]冯芳,丁志建,刘俊.佐剂性关节炎大鼠模型的实验研究[J].天津药学,2004,16(2)：1-4.
[185]徐淑云,卞如濂,陈修.药理实验方法学[M].北京：人民卫生出版社,1991,723-725.