附子-甘草对离体大鼠衰竭心脏的影响及其指纹图谱研究
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摘要
目的研究附子-甘草合煎液及单煎后合并液对离体大鼠心脏的作用及其物质基础。方法使用低钙K-H液灌流制备离体大鼠衰竭心脏模型。用附子单煎、附子-甘草合煎及单煎后合并水提液分别对离体心脏进行干预。采用左室内压(LVSP)、左室内压变化速率(±dp/dt_(max))为指标,观察药物对离体大鼠心脏的作用及其量效关系;运用总量统计矩法研究附子单煎,附子、甘草合煎及附子、甘草单煎后合并液的HPLC指纹图谱及变化,探讨其作用的物质基础。结果各组在给予药液灌流10 min后,各指标的恢复率均有所升高。其中附子生药量为0.1和0.2 mg时,附子配伍甘草后各指标的恢复率均高于附子单煎液;在附子生药量0.4、0.8或1.6 mg时,附子配伍甘草后各指标的恢复率均低于附子单煎液。附子-甘草煎液指纹图谱的统计矩参数如下:附子-甘草合煎液总量一阶矩(λ_(T,i=1))的加合性为100.95%,总量二阶矩(σ_(T,i=1)~2)的加合性为96.55%,平均加合性为70.13%;附子-甘草合并液λ_(T,i=1)的加合性为97.55%,σ_(T,i=1)~2的加合性为96.92%,平均加合性为95.45%。结论若附子、甘草按1∶1配伍,在附子生药量为0.1和0.2 mg时,配伍甘草能够增加其强心作用;在附子生药量为0.4、0.8或1.6 mg时,配伍甘草则减弱其强心作用。附子-甘草合煎液与合并液的化学成分存在差异。
Objective To determine the effect of aconite-licorice combined decoction and its mixed decoction on isolated rat hearts and its material basis. Methods The isolated rat heart model was prepared by perfusion of K-H solution. The isolated hearts were intervened with aconite single decoction, aconite-licorice combined decoction and its mixed decoction. The left ventricular pressure(LVSP) and left ventricular pressure change rate(±dp/dtmax) were used as indicators to observe the effect of drugs on isolated rat hearts and its dose-effect relationship. The total quantum statistical moment method was used to determine the changes in fingerprint parameters of aconite single decoction,aconite-licorice combined decoction and mixed decoction, and the material basis explored. Results The recovery rates of three indexes were increased after the 10 min perfusion. When the crude drug content of aconite reached 0.1 mg or 0.2 mg, the recovery rates of the three indexes after the compatibility of aconite and licorice were higher than that of aconite single decoction. When the crude drug content was 0.4, 0.8 or 1.6 mg, the recovery rates of the three indexes after the compatibility of aconite and licorice were lower than that of aconite single decoction. The statistical moment parameters of the fingerprints of aconite-licorice decoction were as follows: the additional parameter of combined decoction λ_(T,i = 1) was 100.95%, σ_(T,i = 1)~2 was 96.55%, and the average additional parameter was 70.13%.The additional parameter of mixed decoction λ_(T,i = 1) was 97.55%, σ_(T,i = 1)~2 was 96.92%, and the average additional parameter was 95.45%. Conclusion When aconite-licorice compatibility is 1∶1, and the crude drug content of aconite reached 0.1 or 0.2 mg, the combination of aconite and licorice increases the cardiotonic effect of aconite. When the crude drug content is 0.4, 0.8 or 1.6 mg, the combination of aconite and licorice may inhibit the cardiotonic effect of aconite. The chemical constituents of aconite-licorice combined decoction and mixed decoction are different.
Objective To determine the effect of aconite-licorice combined decoction and its mixed decoction on isolated rat hearts and its material basis. Methods The isolated rat heart model was prepared by perfusion of K-H solution. The isolated hearts were intervened with aconite single decoction, aconite-licorice combined decoction and its mixed decoction. The left ventricular pressure(LVSP) and left ventricular pressure change rate(±dp/dtmax) were used as indicators to observe the effect of drugs on isolated rat hearts and its dose-effect relationship. The total quantum statistical moment method was used to determine the changes in fingerprint parameters of aconite single decoction,aconite-licorice combined decoction and mixed decoction, and the material basis explored. Results The recovery rates of three indexes were increased after the 10 min perfusion. When the crude drug content of aconite reached 0.1 mg or 0.2 mg, the recovery rates of the three indexes after the compatibility of aconite and licorice were higher than that of aconite single decoction. When the crude drug content was 0.4, 0.8 or 1.6 mg, the recovery rates of the three indexes after the compatibility of aconite and licorice were lower than that of aconite single decoction. The statistical moment parameters of the fingerprints of aconite-licorice decoction were as follows: the additional parameter of combined decoction λ_(T,i = 1) was 100.95%, σ_(T,i = 1)~2 was 96.55%, and the average additional parameter was 70.13%.The additional parameter of mixed decoction λ_(T,i = 1) was 97.55%, σ_(T,i = 1)~2 was 96.92%, and the average additional parameter was 95.45%. Conclusion When aconite-licorice compatibility is 1∶1, and the crude drug content of aconite reached 0.1 or 0.2 mg, the combination of aconite and licorice increases the cardiotonic effect of aconite. When the crude drug content is 0.4, 0.8 or 1.6 mg, the combination of aconite and licorice may inhibit the cardiotonic effect of aconite. The chemical constituents of aconite-licorice combined decoction and mixed decoction are different.
引文
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[10]王小晓,王幼平,余海滨,等.大鼠Langendorff离体心脏灌流模型的制备经验及其影响因素分析[J].中药药理与临床,2014,30(6):184-186.
[11]贾雪岩,林华,沈玉巧,等.附子新型炮制品中乌头类生物碱测定及其强心作用研究[J].药物评价研究,2016,39(2):224-229.
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[14]王立岩,张志仁,王奕琛,等.附子炮制前后对急性心衰大鼠血流动力学的影响[J].时珍国医国药,2009,20(6):1327-1328.
[15]陈荣昌,孙桂波,张强,等.附子毒性研究进展[J].中国中药杂志,2013,38(8):1126-1129.
[16]伍勇,胡锋,王亚丽,等.减阻剂减轻大鼠离体心脏缺血/再灌注损伤的作用[J].心脏杂志,2017,29(2):22-26.
[17]刘璐,任艳红,张洁,等.白桦脂醇对阿霉素所致大鼠心脏损害保护作用的研究[J].毒理学杂志,2017,31(6):456-459.
[18]熊秋韵,李梦婷,缪璐琳,等.附子不同炮制品抗炎、镇痛和提高免疫功能作用的比较研究[J].中药药理与临床,2017,33(1):123-127.
[19]张广平,解素花,朱晓光,等.附子甘草配伍减毒增效/存效实验研究[J].中国中医药信息杂志,2012,19(6):31-34.
[20]林彦君,游宇,季宁平,等. HPLC-Q-TOF/MS指纹技术对比分析附子配伍炙甘草前后化学组分变化[J].中草药,2014,45(11):1556-1560.
[21]周晋,邓凯文,段晓鹏,等.指纹图谱总量统计矩分析法参数的计算及积分条件的确定[J].中华中医药学刊,2012,30(3):505-508.
[2]张广平,朱丽君,周娟,等.附子配伍甘草对CYP3A4体内活性的影响研究[J].中国中药杂志,2012,37(15):2206-2209.
[3]何瑶,章津铭,高飞,等.附子甘草配伍减毒增效作用机制研究进展及展望[J].中药与临床,2013,4(3):62-65.
[4]秦素红,章津铭,何宇新,等.基于化学组分动态变化的附子配伍甘草煎煮条件研究[J].中国实验方剂学杂志,2012,18(24):20-24.
[5]贺福元,邓凯文,刘文龙,等.中药复方药物动力学总量统计矩法的实验验证研究[J].中国中药杂志,2013,38(2):490-495.
[6]周晋,邓凯文,贺福元,等.总量统计矩分析法定性定量分析补阳还五汤提取物HPLC指纹图谱[J].中药材,2012,35(1):133-137.
[7]李昌伟.地高辛烷亚基强心作用衍生物的筛选[D].郑州:郑州大学,2012.
[8]李冰洁,沈勇,廖日滔,等.从蛋白质自组装的角度探析甘草附子配伍减毒机制[J].中国中药杂志,2015,40(4):661-666.
[9]王志琪,曾嵘,谭志荣,等.附子与甘草配伍前后乌头碱和甘草次酸在大鼠体内的药动学比较[J].中成药,2012,34(12):2305-2309.
[10]王小晓,王幼平,余海滨,等.大鼠Langendorff离体心脏灌流模型的制备经验及其影响因素分析[J].中药药理与临床,2014,30(6):184-186.
[11]贾雪岩,林华,沈玉巧,等.附子新型炮制品中乌头类生物碱测定及其强心作用研究[J].药物评价研究,2016,39(2):224-229.
[12]Huang WW,Wang MY,Shi HM,et al. Comparative study of bioactive constituents in crude and processed Glycyrrhizae radix and their respective metabolic profiles in gastrointestinal tract in vitro by HPLC-DAD and HPLCESI/MS analyses[J]. Arch Pharm Res,2012,35(11):1945-1952.
[13]Tak S,Lakhotia M,Gupta A,et al. Aconite poisoning with arrhythmia and shock[J]. Indian Heart J,2016,68(S2):S207-S209.
[14]王立岩,张志仁,王奕琛,等.附子炮制前后对急性心衰大鼠血流动力学的影响[J].时珍国医国药,2009,20(6):1327-1328.
[15]陈荣昌,孙桂波,张强,等.附子毒性研究进展[J].中国中药杂志,2013,38(8):1126-1129.
[16]伍勇,胡锋,王亚丽,等.减阻剂减轻大鼠离体心脏缺血/再灌注损伤的作用[J].心脏杂志,2017,29(2):22-26.
[17]刘璐,任艳红,张洁,等.白桦脂醇对阿霉素所致大鼠心脏损害保护作用的研究[J].毒理学杂志,2017,31(6):456-459.
[18]熊秋韵,李梦婷,缪璐琳,等.附子不同炮制品抗炎、镇痛和提高免疫功能作用的比较研究[J].中药药理与临床,2017,33(1):123-127.
[19]张广平,解素花,朱晓光,等.附子甘草配伍减毒增效/存效实验研究[J].中国中医药信息杂志,2012,19(6):31-34.
[20]林彦君,游宇,季宁平,等. HPLC-Q-TOF/MS指纹技术对比分析附子配伍炙甘草前后化学组分变化[J].中草药,2014,45(11):1556-1560.
[21]周晋,邓凯文,段晓鹏,等.指纹图谱总量统计矩分析法参数的计算及积分条件的确定[J].中华中医药学刊,2012,30(3):505-508.