免费文献传递   相关文献

灯台叶碱抗炎镇痛作用研究



全 文 :灯台叶碱抗炎镇痛作用研究
杨坤芬,赵云丽,尚建华
(云南省药物研究所,云南 昆明 650111)
  摘 要:目的:研究灯台叶碱抗炎、镇痛作用,为临床应用
提供实验依据。方法:采用二甲苯致小鼠耳廓肿胀、鸡蛋清致
大鼠足趾肿胀、大鼠慢性肉芽肿炎症模型,小鼠醋酸致痛模
型,观察研究灯台叶碱的抗炎、镇痛作用。结果:灯台叶碱连
续灌胃给药3d,能明显抑制二甲苯致小鼠耳廓肿胀和蛋清致
大鼠足趾肿胀;一次给药,能明显抑制醋酸所致小鼠的扭体性
疼痛;连续灌胃给药10d,能明显抑制大鼠慢性棉球肉芽肿。
结论:灯台叶碱具有明显的抗炎、镇痛作用,研究结果为临床
应用提供了实验依据。
关键词:灯台叶碱;抗炎;镇痛
中图分类号:R285 文献标识码:A
文章编号:1007-2349(2012)04-0061-02
灯台叶为云南特色天然民族药,其粗提物制剂“灯台叶颗
粒”和“灯台叶片”已上市使用多年,安全性和有效性均得到临
床验证。灯台叶碱,是从灯台叶中提取分离的有效部位,具有
止咳平喘、清热解毒的功效,用于急性气管-支气管炎、慢性
支气管炎急性发作期(风热袭肺证),症见咳嗽、咯痰、发热、咽
痒不适、恶风、气急、头痛、口渴、尿黄。本文主要考察灯台叶
碱的抗炎、镇痛作用,并与市售“灯台叶片”进行比较,为深度
开发的必要性和临床应用提供实验依据。
1 材料
1.1 药品与试剂 灯台叶碱,棕黄色粉末,水中混悬,常温密
闭保存,批号20070512(含量53.58%),由中科院昆明植物研
究所和云南省药物研究共同研制提供;灯台叶片,国药准字
Z20025348,0.3g/片,云南大唐汉方制药有限公司,批号
060803;阿斯匹林肠溶片(拜阿斯匹灵、ASP),进口药品注册
证号 H20050059,100mg/片,Bayer Health Care AG生产,批
号BTA4RE2;醋酸泼尼松片,国药准字 H33021207,5mg/片,
浙江仙居制药股份有限公司,批号061112;冰醋酸,分析纯,天
津市化学试剂三厂,批号20030908;二甲苯,分析纯,天津市致
远化学试剂有限公司,批号2006-10-15;羧甲基纤维素钠,
化学纯,国药集团化学试剂有限公司,批号F20040826;鸡蛋
清,取自农户家产3日内的鲜蛋。
1.2 主要仪器 AL104型电子分析天平,梅特勒-托利多仪
器(上海)有限公司;JJ2000电子天平,常熟市双杰测试仪器
厂;PV-200型足趾容积测量仪,成都泰盟科技有限公司;101
型电热鼓风干燥箱,北京仪器有限公司。
1.3 动物 SPF级ICR小鼠,雌雄兼用,体重19~24g;SPF
级雄性SD大鼠,体重170~240g;动物生产许可证:SCXK
(滇)2005-0008,饲料生产许可证:SCXK(滇)2005-000 9;
均由昆明医学院实验动物中心提供。
透明塑料盒群养,雌雄分笼,小鼠每箱≤10只,大鼠每
箱≤6只;饲养于IVC动物实验室,温度20~25 ℃(日温
差≤3℃);湿度40%~70%;照明12h:12h明暗交替,照度
150~300lx;噪音≤60dB。实验动物使用许可证号:SYXK
(滇)2005-0001。每日喂饲鼠用配合饲料,自由饮水,视情况
更换笼具和垫料;
2 方法与结果
2.1 抗炎作用研究
2.1.1 对二甲苯致小鼠耳廓肿胀的影响[1]选用19~22g小
鼠70只,雌雄各半,按体重和性别随机分为7组,每组10只。
除阿斯匹林组仅于实验当天灌胃给药1次外,其余各组均预
先每日灌胃给药1次,连续3天,对照组灌服等容量1%
CMC-Na,各组灌胃容积均为20mL/kg.bw。末次灌胃后
30min,各组小鼠于右耳两面均匀涂抹二甲苯0.05mL/只,左
耳不涂为对照。致炎后1h脱颈椎处死动物,用直径8mm的
打孔器于双耳同部位等面积切下,以两耳片重量之差作为肿
胀度。结果见表1。
表1 灯台叶碱对二甲苯致小鼠耳廓肿胀的影响
组 别 剂量(/kg) 动物数(只)耳廓肿胀度(-x ±s,mg)抑制率(%)
对照 — 10  9.95±1.91 —
ASP  0.2g  10  2.85±3.06** 71.36
灯台叶片 1.2g  10  5.10±2.85** 48.74
10mg  10  5.50±2.07** 44.72
灯台叶碱
20mg  10  4.35±2.37** 56.28
40mg  10  2.61±2.55** 73.77
80mg  10  2.62±2.02** 73.65
  与对照组相比,**P<0.01
由表1可见,阿司匹林、灯台叶片及灯台叶碱10、20、40、
80mg/kg剂量连续灌胃给药3d,均能明显抑制二甲苯致小
鼠的耳廓肿胀,与对照组相比差异非常显著;灯台叶碱10、
20mg/kg剂量的作用与 1.2g/kg的灯台叶片相当,40、
80mg/kg的作用又与0.2g/kg阿司匹林相当,均强于1.2g/
kg的灯台叶片。
2.1.2 对蛋清致大鼠足跖肿胀的影响[1]取170~220g雄性
SD大鼠70只,按体重随机分为7组,每组10只,给药方法同
2.1.1,给药容积为10mL/kg.bw。末次给药后30min,于每
162012年第33卷第4期          云 南 中 医 中 药 杂 志
DOI:10.16254/j.cnki.53-1120/r.2012.04.027
鼠右后足跖皮下注射新鲜蛋清0.1mL致炎。分别测定致炎
前及致炎后0.5、1、2、3、4h的足容积,以致炎前后足容积的差
值作为肿胀度,并计算肿胀率。结果见表2。
肿胀率=(给药后足容积-给药前足容积)÷给药前足
容积
表2 灯台叶碱对蛋清致大鼠足跖肿胀的影响(n=10)
组 别
剂量
(/kg)
基础容积
(-x ±s,mL)
致炎后足跖肿胀率(-x ±s)
30min  1h 2h 3h 4h
对照 — 1.40±0.08 0.67±0.11 0.66±0.11 0.62±0.10 0.54±0.10  0.46±0.09
ASP  0.2g 1.41±0.09 0.53±0.12*0.51±0.13*0.44±0.14**0.39±0.14* 0.33±0.11*
灯台叶片 0.9g 1.41±0.09 0.56±0.11*0.54±0.09*0.51±0.10*0.48±0.08  0.41±0.08
15mg 1.40±0.09 0.61±0.14 0.59±0.12 0.55±0.13 0.50±0.14  0.44±0.11
灯台叶碱
30mg 1.40±0.06 0.57±0.10 0.53±0.11*0.48±0.14*0.43±0.09* 0.39±0.07*
60mg 1.40±0.08 0.58±0.14 0.52±0.11*0.45±0.10**0.41±0.11**0.37±0.10
120mg 1.40±0.05 0.56±0.10*0.56±0.08*0.49±0.08**0.46±0.07  0.39±0.07
  与对照组相比:*P<0.05,**P<0.01
由表2可见,阿司匹林、灯台叶片及灯台叶碱以30、60、
120mg/kg的剂量连续灌胃给药3天,均能明显抑制蛋清所
致大鼠的足跖肿胀;30mg/kg剂量的灯台叶碱作用持续时间
比灯台叶片长,但短于阿司匹林组。
2.1.3 对大鼠棉球肉芽肿的影响[1] 取180~240g雄性SD
大鼠70只,按体重随机分为7组,每组10只。各鼠于消毒条
件下在左右后肢蹊部皮下各植入(20.0±1.0)mg灭菌棉球1
个(植入前加青霉素和链霉素混合液0.2mL浸润、60℃烘
干),手术当日各组动物开始按剂量灌胃给药,每日1次,连续
10天。第11日禁食不禁水12h后称重,脱颈椎处死大鼠,将
棉球连同周围结缔组织一起取出,剔除脂肪组织,于60℃烘
箱内干燥24h后称重,减去棉球重量即为肉芽净重;按体重折
算成肉芽系数(每100g体重所占的肉芽肿重量),并与对照组
比较各给药组对棉球肉芽肿的抑制率。结果见表3。
抑制率=(对照组肉芽系数-给药组肉芽系数)÷对照组
肉芽系数×100%
表3 灯台叶碱对大鼠棉球肉芽肿的影响(n=10)
组别
剂量
(/kg)
肉芽
净重(mg)
系数(-x ±s)
(mg/100g)
抑制率(%)
对照 — 110.52±31.49  57.18±27.68 —
醋酸泼尼松 10mg 76.85±12.06** 37.18±6.33* 34.98
灯台叶片 0.9g 70.99±25.33** 33.44±12.90* 41.51
15mg 76.64±9.64** 35.81±4.07* 37.37
灯台叶碱
30mg 75.61±7.43** 33.69±3.47* 41.07
60mg 72.57±9.05** 34.42±4.95* 39.80
120mg 77.69±9.33** 37.03±5.63* 35.24
  与对照组相比,*P<0.05,**P<0.01
由表3可见,醋酸泼尼松、灯台叶片及灯台叶碱以15、30、
60、120mg/kg的剂量连续灌胃给药10d,均能明显抑制大鼠
皮下棉球肉芽肿的生成,各组间抑制率无明显差异。
2.2 对醋酸致小鼠扭体性疼痛的影响[1] 选用20~24g
ICR小鼠70只,雌雄各半,按性别和体重随机分为7组,每组
10只。各组动物分别按剂量灌胃给药1次,对照组灌服等容
量1%CMC-Na,容积均为20mL/kg体重。给药后30min,
每鼠腹腔注射0.6%冰醋酸溶液0.1mL/10g体重,观察并记
录15min内各鼠因疼痛引起的扭体次数,计算抑制率。为消
除系统误差,实验采用平行操作。结果见表4。
表4 灯台叶碱对醋酸致小鼠疼痛的影响
组别 剂量(/kg) 扭体次数(-x ±s,次) 抑制率(%)
对照 — 25.6±9.4 —
ASP  0.2g  14.0±11.3* 45.31
灯台叶片 1.2g  30.5±12.8 -19.14
10mg  18.8±6.2△ 26.56
灯台叶碱
20mg  11.8±10.2**△ 53.91
40mg  13.7±7.2**△△ 46.48
80mg  12.0±10.1**△△ 53.13
   与对照组相比,*P<0.05,**P<0.01;与灯台叶片相比,
△P<0.05,△△P<0.01
由表4可见,灯台叶碱以10、20、40及80mg/kg的剂量
单次灌胃给药,能不同程度抑制醋酸所致小鼠的扭体性疼痛,
10mg/kg剂量有作用趋势,其余3剂量组与对照组相比差异
均有统计学意义;3剂量组的作用强度与0.2g/kg阿司匹林
相当;1.2g/kg的灯台叶片无抑制作用。
3 讨论
急性支气管炎通常是由病毒或细菌感染引起的气管-支
气管黏膜炎症,而慢性支气管炎是由于感染或非感染因素引
起气管、支气管黏膜及其周围组织的慢性非特异性炎症。本
研究围绕灯台叶碱的临床适应症,选择多种动物实验模型,观
察灯台叶碱对镇痛及抗炎作用的影响。结果表明,灯台叶碱
能明显抑制醋酸所致小鼠的扭体性疼痛,明显抑制二甲苯致
小鼠耳廓炎症和蛋清所致大鼠足趾肿胀,并对大鼠棉球肉芽
肿有明显抑制作用。提示灯台叶碱提具有镇痛、抗炎作用,可
能对感冒和支气管炎引起的疼痛、继发性感染的炎症有预防
或治疗作用。研究结果为灯台叶碱的临床应用提供了实验
依据。
参考文献:
[1]陈奇 .中药药理实验方法[M].北京:人民卫生出版社,1994:
308~378.
(收稿日期:2012-02-16)
26 云 南 中 医 中 药 杂 志          2012年第33卷第4期
Yunnan Journal of Traditional Chinese Medicine and Materia Medica
Vol. 33. No. 4 (General No. 226) April,2012
Main Content
Study on the Effect of Fuzheng Xiaoji Recipe Combined with Chemotherapy on the Life Quality and Serum Tumor Markers of
Late Breast Cancer Patients
XIONG Liang-geng…………………………………………………………………………………………………………………………………………
Analysis of the Correlation between Essential Hypertension and Lipid in TCM Syndrome in Southern Sichuan Area
LIAO Hui-ling,YIN Si-yuan,GE Chun-li,et al……………………………………………………………………………………………………………
Determination of the Content of Palmatine in Fibrauretin Pellets Capsule by HPLC
LIU Bo,YANG Hui,WANG Jing-kun……………………………………………………………………………………………………………………
Study on the Anti-inflammatory and Analgesic Effects of Alkaloid in Alstonia Scholaris Leaf
YANG Kun-fen,ZHAO Yun-li,SHANG Jian-hua…………………………………………………………………………………………………………
Study on the Effect of Fuzheng Xiaoji Recipe Combined with Chemotherapy on the Life Quality and Serum Tumor Markers of
Late Breast Cancer Patients
XIONG Liang-geng
(Oncology Department,Second People’s Hospital of Dazhou City,Dazhou,Sichuan,635000)
Abstract:Objective:To observe the effect of Fuzheng Xiaoji recipe combined with chemotherapy on the life quality and serum tumor markers of late
breast cancer patients. Methods:48 patients were randomly divided into one treatment group and one control group,24 patients per group. The patients of the
two groups are treated with capecitabine and vinorelbine,but the patients in the treatment group were added with Fuzheng Xiaoji recipe. The recent efficacy,
life quality and serum tumor markers of the patients in the two groups were observed in four weeks. Results:A. in short-term effect:the response rate (RR)
of treatment group was 50. 0% while that of the control group was 41. 7% and the comparison of the two groups showed no statistical significance (P > 0. 05).
The disease control rate (DCR)of the treatment group was 87. 5% while that of the control group was 58. 3%,and the comparison showed significant
differences (P < 0. 05). B. in the changes of the life quality:the effective rates of the treatment group and control group were 87. 5% and 54. 2%
respectively,showing significant differences (P < 0. 05). C. serum tumor markers:CEA,CA 125,CA 15 - 32 of the two groups showed more significant
differences before and after the treatment. The three markers of the treatment group were remarkably lower than that of the control group (P < 0. 05).
Conclusion:Fuzheng Xiaoji recipe combined with chemotherapy can improve the life quality of the late breast cancer patients and reduce their serum tumor
markers and enhance their efficacy and prolong their survival time.
Key words:late breast cancer;Fuzheng Xiaoji recipe;chemotherapy;short-term efficacy;life quality;serum tumor marker
Analysis of the Correlation between Essential Hypertension and Lipid in TCM Syndrome in Southern Sichuan Area
LIAO Hui-ling,YIN Si-yuan,GE Chun-li
(School of Chinese and Western Integrative Medicine,Luzhou Medical College,Luzhou,Sichuan,646000)
Abstract:Objective:To study the relationship of lipids and essential hypertension in Southern Sichuan area. Methods:140 essential hypertension
patients and 40 normal blood pressure persons in Luzhou of Sichuan province were detected to compare their blood pressures and lipids. Results:In the four
types of high blood pressure syndromes above,TG of the liver-fire hyperactivity type,yin deficiency and yang preponderance type,excessive phlegm type and
normal people showed a significant difference statistically(P < 0. 05). The TG comparison of the excessive phlegm and the yin and yang deficiency had a
significant difference statistically (P < 0. 05). The TG comparison of the yin deficiency and yang preponderance and the excessive phlegm also had a
significant difference statistically (P < 0. 05). LDL of the yin and yang deficiency in the all syndromes increased significantly,and the comparison of the liver-
fire hyperactivity,the yin deficiency and yang preponderance and normal people had statistical significance (P < 0. 05). Conclusion:A. The increase of TG
and reduction of HDL-C can be used as objective indices of phlegm-dampness type. B. The rising of LDL-C can be used as objective indices of yin and yang
deficiency. C. The patients of the excessive phlegm have a risk of AS and CHD in hypertension of TCM syndromes.
Key words:hypertension;TCM syndrome;lipids;correlation
Determination of the Content of Palmatine in Fibrauretin Pellets Capsule by HPLC
LIU Bo,YANG Hui,WANG Jing-kun
(Yunnan Institute of Pharmacology,Kunming,Yunnan,650111)
Abstract:Objective:To establish a HPLC method for the determination of palmatine content in the fibrauretin pellets capsule. Methods:HPLC was used
to determine the content of palmatine in the fibrauretin pellets capsule. Results:The range of palmatine was 0. 131 ~ 1. 572 μg and the peak area showed a
good linear relationship (r = 0. 999 84)and the average recovery rate was 100. 48%,RSD = 2. 46% (n = 9). Conclusion:This method is simple,accurate
with good repeatability and can be used for the determination of the content of the palmatine pellets capsules.
Key words:fibrauretin pellets capsule;HPLC;palmatine;content determination
Study on the Anti-inflammatory and Analgesic Effects of Alkaloid in Alstonia Scholaris Leaf
YANG Kun-fen,ZHAO Yun-li,SHANG Jian-hua
(Yunnan Institute of Pharmacology,Kunming,Yunnan,650111)
Abstract:Objective:To study the anti-inflammatory and analgesic effect of the alkaloid in alstonia scholaris leaf and provide an experimental basis for
clinical application. Methods:The models of xylene-induced ear swelling mice,egg whites-induced paw swelling rats,chronic granulomatous inflammation rats
and acetic acid-induced painful mouse were made to observe the anti-inflammatory and analgesic effects of the alkaloid in alstonia scholaris leaf. Results:The
alkaloid of alstonia scholaris leaf was administered to the animals for 3 days,significantly inhibiting the xylene-induced ear swelling mice and egg white-induced
paw swelling rats. One administration obviously inhibited the writhing pain caused by acetic acid and continuous administrations for 10 days significantly
inhibited the chronic granulomatous inflammation rats. Conclusion:The alkaloid of the alstonia scholaris leaf has significant anti-inflammatory and analgesic
effects and the results provide an experimental basis for its clinical application.
Key words:alkaloid of alstonia scholaris leaf;anti-inflammatory;analgesic