
浏览全部资源
扫码关注微信
福建中医药大学 药学院,福州 350122
杨苗苗,在读硕士,从事中药制剂及质量控制方面研究,E-mail:ymm9698@163.com
李孝栋,博士,教授,硕士生导师,从事中药物质基础、中药药物制剂及其复杂体系药代动力学的研究,E-mail: lxdtcm@163.com
收稿日期:2018-10-22,
网络出版日期:2019-02-12,
纸质出版日期:2019-08-20
移动端阅览
杨苗苗, 陈燕, 杨霖, 等. 生乌头与制乌头提取物的药理评价[J]. 中国实验方剂学杂志, 2019,25(16):44-49.
Miao-miao YANG, Yan CHEN, Lin YANG, et al. Pharmacological Evaluation for Extracts of Aconiti Radix and Aconiti Radix Cocta[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 44-49.
杨苗苗, 陈燕, 杨霖, 等. 生乌头与制乌头提取物的药理评价[J]. 中国实验方剂学杂志, 2019,25(16):44-49. DOI: 10.13422/j.cnki.syfjx.20191023.
Miao-miao YANG, Yan CHEN, Lin YANG, et al. Pharmacological Evaluation for Extracts of Aconiti Radix and Aconiti Radix Cocta[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 44-49. DOI: 10.13422/j.cnki.syfjx.20191023.
目的:
2
开展生乌头与制乌头提取物的药理研究与处方原料选择的评价,促进乌头类制剂的发展和临床应用。
方法:
2
按照乌头注射液的工艺,制得生草乌与生川乌(合称生乌头)以及制草乌与制川乌(合称制乌头)的混合提取物,以生药0.152 5 mg·g
-1
为基础,配得生乌头与制乌头的不同剂量组,开展了镇痛、减慢心率、抑癌等药效和急性毒性、脏器观察等毒理实验,进行系统的分析与评价。
结果:
2
与空白组比较,生乌头与制乌头提取物均具有显著的镇痛作用,给药剂量相同时,生乌头注射液的疼痛抑制率(60.91%)比制乌头注射液的(53.42%)大,口服给药的生乌头提取物疼痛抑制率(73.94%)远大于制乌头提取物(29.97%)(
P
<
0.01)。减慢心率实验,大鼠给药后第30 min的心率与0 min心率相比,随着给药剂量的增加,生乌头组依次呈现减慢、平稳、加快的趋势,制乌头组则表现为平稳、减慢、加快的顺序,表明生乌头提取物低剂量时可达到减慢心率的作用。噻唑蓝(MTT)比色法结果显示,生乌头与制乌头提取物均具有明显抑制胃癌AGS细胞增殖的作用,剂量相同时,生乌头提取液的抑制作用较制乌头的更强。大鼠急性毒性实验测得生乌头与制乌头提取液的半数致死量(LD
50
)分别为3.9,21.0 g·kg
-1
,相当于临床剂量的4,20倍,制乌头的LD
50
是生乌头的5倍。中毒致死大鼠的解剖发现,肝、肾等脏器均已发黑,中毒症状明显,而临床及其以下剂量的大鼠,各脏器均为正常。
结论:
2
生乌头安全性比制乌头的小,但镇痛、减慢心率与抑癌作用来的大,建议乌头注射液等制剂在治疗胃、肝癌晚期等重症疼痛时,原料选用生乌头,治疗一般疼痛的乌头制剂选用制乌头提取物为处方,做到真正安全与疗效相结合地辨证施治。
Objective:
2
To carry out the studies of pharmacological action for extracts of Aconiti Radix and Aconiti Radix Cocta
and evaluate the selection of raw materials in prescriptions
in order to promote the development and clinical application of preparations.
Method:
2
The mixed extracts of Aconiti Radix and Aconiti Radix Cocta were prepared respectively according to the technique of aconitum injection
and different dose groups of Aconiti Radix and Aconiti Radix Cocta were established based on the dose of Aconiti Radix 0.152 5 mg·g
-1
and then applied in such pharmacodynamic tests as analgesia
heart rate reduction
antitumor effect and toxicology tests
such as acute toxicity and organ observation. The data were analyzed systematically on the basis of literatures.
Result:
2
Compared with blank group
the extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly analgesic effect. At the same dose
the pain inhibition rate of Aconiti Radix injection (60.91%) was higher than that of Aconiti Radix Cocta injection (53.42%)
and the pain inhibition rate of Aconiti Radix extract for oral administration(73.94%) was also much higher than that of Aconiti Radix Cocta extract (29.97%)
with significant differences (
P
<
0.01). In terms of heart rate reduction test
the heart rate of rats at 0 min was compared with that at 30
th
min after administration
the heart rate of the Aconiti Radix group was decreased first
then stabilized
and finally increased with the rise of the dose
while for the Aconiti Radix Cocta group showed a different trend of first stability
then decrease and finally increase. The result indicated the Aconiti Radix group had the effect in reducing heart rate in rats at a low dose. The survival inhibition rate was evaluated by 3-(4
5-Dimethylthiazol-2-yl)-2
5-diphenyltetrazolium bromide (MTT). The extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly inhibitory effect on the proliferation of AGS gastric cancer cells
in which Aconiti Radix was stronger than that of Aconiti Radix Cocta at the same dose. In the acute toxicity test of rats
lethal dose 50%(LD
50
) of Aconiti Radix and Aconiti Radix Cocta were 3.9 g·kg
-1
and 21.0 g·kg
-1
respectively
which were equivalent to 4 times and 20 times of the clinical dose. LD
50
of the extract of Aconiti Radix Cocta was 5 times than that of Aconiti Radix. The liver and kidney of dead rats were dark with obvious symptoms of poisoning after dissection
while all the organs of rats at the clinical and lower dose were normal.
Conclusion:
2
The safety of Aconiti Radix is lower than that of Aconiti Radix Cocta
but with greater analgesic
bradycardic and anticancerous effect. Therefore
it is suggested that the preparations
such as aconitum injection
should be prepared with Aconiti Radix in the treatment of severe pain of patients with advanced gastric and liver cancer
and the preparations for general pain can be prepared with Aconiti Radix Cocta
so as to achieve a truly safe and effective dialectical treatment.
饶冉 . 乌头属药用植物研究进展 [J]. 安徽农业科学 , 2012 , 40 ( 29 ): 14227 - 14230 .
李梦然 , 曲玮 , 梁敬钰 . 乌头属化学成分和药理作用研究进展 [J]. 海峡药学 , 2010 , 22 ( 4 ): 1 - 6 .
吴超 , 赵翡翠 . 我国乌头属植物研究进展 [J]. 新疆医科大学学报 , 2011 , 34 ( 10 ): 1153 - 1157 .
国家药典委员会 . 中华人民共和国药典 . 一部 [M]. 北京 : 中国医药科技出版社 , 2015 : 39,236 .
田伟珍 , 叶海霞 . 21例乌头碱类中药中毒的急救护理 [J]. 现代中西医结合杂志 , 2008 , 17 ( 12 ): 1901 .
李谦 , 过立农 , 郑健 , 等 . 乌头属药用植物的研究进展 [J]. 药物分析杂志 , 2016 , 36 ( 7 ): 1129 - 1149 .
赵翡翠 , 李杰 . 乌头属药用植物中生物碱的研究进展 [J]. 中国现代应用药学 , 2010 , 27 ( S1 ): 1177 - 1182 .
王彬辉 , 冯健 , 赵燕敏 , 等 . 附子中乌头类生物碱在大鼠体内的药动学研究 [J]. 中国药学杂志 , 2009 , 44 ( 18 ): 1412 - 1415 .
武洁 , 沈红 , 朱玲英 , 等 . 液-质联用法同时测定大鼠血浆中的乌头碱、新乌头碱、次乌头碱及其药动学 [J]. 中国医院药学杂志 , 2011 , 31 ( 14 ): 1162 - 1166 .
陶长戈 , 李文军 , 彭成 . 附子总生物碱中乌头碱、新乌头碱、次乌头碱在大鼠体内的药动学研究 [J]. 云南中医中药杂志 , 2011 , 32 ( 3 ): 49 - 52 .
杨蕾 , 陈裕明 , 刘启福 , 等 . 川乌饮片急毒及药效学的实验比较 [J]. 北京中医药大学学报 , 1997 , 20 ( 2 ): 20 - 21 .
李志勇 , 张硕峰 , 畅洪昇 , 等 . 不同炮制时间附子饮片双酯型生物碱含量变化与饮片安全的相关性研究 [J]. 中国中药杂志 , 2009 , 34 ( 9 ): 1086 - 1089 .
付雯雯 , 薛岩 , 刘军 , 等 . 乌头注射液对疼痛小鼠的镇痛作用 [J]. 中国老年学杂志 , 2015 , 35 ( 17 ): 4768 - 4770 .
黄衍民 , 李成韶 , 潘留华 , 等 . 乌头注射液对小鼠的镇痛作用及其药效动力学研究 [J]. 中国药学杂志 , 2000 , 35 ( 9 ): 37 - 39 .
YANG J , Park K S , Yoon J J , et al . Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord [J]. BMC Complement Alter Med , 2016 , 16 : 214 .
王龙 , 孟志雄 . 乌头注射液联合FP方案治疗消化道恶性肿瘤疗效观察 [J]. 甘肃医药 , 2009 , 28 ( 4 ): 297 - 299 .
雷桂华 . 乌头注射液联合化疗的临床效果观察 [J]. 肿瘤防治杂志 , 2001 , 8 ( 3 ): 295 - 296 .
《中华人民共和国部颁药品标准(中药)》编委会 . 中华人民共和国部颁药品标准(中药) [M]. 北京 : 中国医药出版社 , 1998 : Z17 - Z20 .
杨凤玉 , 孙海清 . 布洛芬分散片的药效学研究 [J]. 中国医药导报 , 2013 , 10 ( 7 ): 9-10,13 .
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 .
丁芸霞 , 邹玺 , 吴坚 , 等 . 附子生物碱对人胃癌细胞株SGC-7901凋亡及细胞周期的影响 [J]. 世界科学技术—中医药现代化 , 2013 , 15 ( 5 ): 915 - 919 .
张晓迪 , 吴酉霆 . 附子提取物抗胃癌SGC-7901细胞增殖及诱导癌细胞凋亡实验研究 [J]. 浙江中医药大学学报 , 2011 , 35 ( 5 ): 665 - 668 .
顾兵 , 张政 , 李玉萍 , 等 . 半数致死量及其计算方法概述 [J]. 中国职业医学 , 2009 , 36 ( 6 ): 507-508,511 .
孟甄 , 丁怡 , 鲁静 , 等 . 生、制乌头总生物碱对心脏功能及其毒性的比较 [J]. 中国药理学通报 , 2004 , 20 ( 7 ): 801 - 804 .
刘帅 , 刘晓艳 , 李妍 , 等 . 草乌及其炮制品的急性毒性实验研究 [J]. 中国药物警戒 , 2015 , 12 ( 9 ): 513-516,521 .
刘帅 , 李妍 , 李卫飞 , 等 . 乌头类中药毒性及现代毒理学研究进展 [J]. 中草药 , 2016 , 47 ( 22 ) : 4095 - 4102 .
0
浏览量
14
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621