中药痛经巴布剂治疗痛经的实验研究
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摘要
中药痛经巴布剂治疗痛经的实验研究
目的 通过中药痛经巴布剂主要药效学的研究，验证其治疗痛经的有效性；通过皮肤刺激试验，对中药痛经巴布剂的毒理作用有所认识，验证其安全性。
方法 ①扭体试验：SD雌性大鼠随机分为凡士林组(空白对照组)、布洛芬乳膏组(阳性对照组)及痛经巴布剂组(试验药物组)，各组大鼠腹腔注射苯甲酸雌二醇连续10天，第5天起分别用各组相应药物，连续6天。第11天用药40min后，腹腔注射催产素2u／只，记录30min内的扭体反应。②对痛经模型大鼠前列腺素E_2的影响：扭体试验观察完毕后，即刻眼眶取血，取血后立即取出大鼠子宫，称取子宫组织，匀浆，用放免法检测血浆及子宫组织中的PGE_2含量。③对正常家兔子宫平滑肌收缩的影响：雌性家兔腹腔注射苯甲酸雌二醇连续2天，第3天处死，制备离体子宫平滑肌标本，固定在盛有洛氏液的恒温浴皿中。标本平衡后依次加入月月舒冲剂，痛经巴布剂高、低剂量中药原液，用Medlab生物信号采集系统记录给药前后子宫平滑肌的收缩频率、幅度。④对催产素所致家兔子宫平滑肌剧烈收缩的影响(基本方法同③)：将标本平衡并加入催产素，10min后，依次加入各试验药物。⑤皮肤刺激试验：白色家兔设完整皮肤组和破损皮肤组，采用左右侧自身对照，每日给药1次，连续7天，观察7天后及停药一周内的皮肤刺激情况。
结果 ①痛经巴布剂能显著抑制痛经模型大鼠的扭体反
应。②痛经模型大鼠痛经巴布剂组血浆及子宫组织中的PGEZ
含量明显低于空白组，和布洛芬乳膏组相比较血浆中PGEZ含
量有统计学差异而子宫组织中的PGEZ含量无统计学差异。③
痛经巴布剂高、低剂量组能降低家兔正常离体子宫平滑肌的
收缩频率和幅度，降低催产素所致子宫平滑肌剧烈收缩的幅
度，低剂量组和用药前比有统计学差异，高剂量组和用药前
及月月舒冲剂组比较均有统计学差异。④痛经巴布剂无明显
皮肤刺激征。
结论①通过动物实验证实中药痛经巴布剂能够治疗原
发性痛经。②中药痛经巴布剂治疗原发性痛经的作用机制与
其能抑制子宫平滑肌收缩(解痉作用)、降低PGEZ含量及镇
痛作用有关。③皮肤刺激试验初步说明痛经巴布剂是一个安
全的外用制剂。
Experimental Study on Anti-dysmenorrhea Effect of Tongjing Plaster
Objective To study the anti-dysmenorrhea effect and the skin irritation of Tongjing Plaster, which could be a conclusion that Tongjing Plaster can cure primary dysmenorrhea, and has no irritation reaction in skin. Methods (1)Twisting body reaction: SD female rats were divided into three groups randomly, vaseline group, ibuprofen group and Tongjing Plaster group .Intraperitoneal injected estradiol benzoate for 10 days. From the fifth days, each group received the medicine respectively for 6 days. At the eleventh day, intraperitoneal injected oxytocin, recorded twisting numbers of each rat within 30 minutes.(2)The effect on the concentration of PGE2 of rat models of dysmenorrhea: After (1) completed, measured the concentration of PGE2 in blood plasma and uterine tissue by radioimmunoassay(RIA).(3)The effect on extracorporeal uterine smooth muscle of rabbits: Female rabbits were intraperitoneal injected estradiol benzoate for 2 days. At the third day the rabbits were killed ,then measured the extent ,frequency
of the isolated uteri contractions, which influenced by yueyueshu pelletized granule ,high or dosage of Tongjing Plaster respectively .(4)The effect on extracorporeal uterine smooth muscle of rabbits which sensitized by oxytocin: the same method as (3), but the uteri sensitized by oxytocin. (5) Experimental study on skin irritation: hair -cut white rabbits were divided into complete skin group and injured skin group, each group received the
medicine respectively, then judged the results according to " Instructive principle for preclinic study of new Chinese drugs" .
Results (1)Tongjing Plaster evidently inhibited twisting body reaction of rat models of dysmenorrhea. (2) The content of PGEa in blood plasma and uterine tissue of Tongjing Plaster group was evidently under vacuity contrast group, the content in blood plasma of Tongjing Plaster had statistical significant comparing with ibuprofen ,but no statistical significant in uterine tissue.(3)Tongjing Plaster can reduce the frequency and extent of contraction in normal extracorporeal uterine smooth muscle, and reduce the extent of acutely contraction in uterine muscle sensitized by oxytocin. (4) No evidently irritation reaction occurred in either complete skin or injured skin.
Conclusion (1) Tongjing Plaster can cure primary dysmenorrhea. (2) Tongjing Plaster has effect on primary dysmenorrhea, the mechanism related to inhibiting contraction of isolated uteri both in normal and sensitized by oxytocin , reducing the content of PGE2 and the abirritation . (3)Tongjing Plaster has no irritation in skin, which initially proved Tongjing Plaster is a safe medcine.
目的 通过中药痛经巴布剂主要药效学的研究，验证其治疗痛经的有效性；通过皮肤刺激试验，对中药痛经巴布剂的毒理作用有所认识，验证其安全性。
方法 ①扭体试验：SD雌性大鼠随机分为凡士林组(空白对照组)、布洛芬乳膏组(阳性对照组)及痛经巴布剂组(试验药物组)，各组大鼠腹腔注射苯甲酸雌二醇连续10天，第5天起分别用各组相应药物，连续6天。第11天用药40min后，腹腔注射催产素2u／只，记录30min内的扭体反应。②对痛经模型大鼠前列腺素E_2的影响：扭体试验观察完毕后，即刻眼眶取血，取血后立即取出大鼠子宫，称取子宫组织，匀浆，用放免法检测血浆及子宫组织中的PGE_2含量。③对正常家兔子宫平滑肌收缩的影响：雌性家兔腹腔注射苯甲酸雌二醇连续2天，第3天处死，制备离体子宫平滑肌标本，固定在盛有洛氏液的恒温浴皿中。标本平衡后依次加入月月舒冲剂，痛经巴布剂高、低剂量中药原液，用Medlab生物信号采集系统记录给药前后子宫平滑肌的收缩频率、幅度。④对催产素所致家兔子宫平滑肌剧烈收缩的影响(基本方法同③)：将标本平衡并加入催产素，10min后，依次加入各试验药物。⑤皮肤刺激试验：白色家兔设完整皮肤组和破损皮肤组，采用左右侧自身对照，每日给药1次，连续7天，观察7天后及停药一周内的皮肤刺激情况。
结果 ①痛经巴布剂能显著抑制痛经模型大鼠的扭体反
应。②痛经模型大鼠痛经巴布剂组血浆及子宫组织中的PGEZ
含量明显低于空白组，和布洛芬乳膏组相比较血浆中PGEZ含
量有统计学差异而子宫组织中的PGEZ含量无统计学差异。③
痛经巴布剂高、低剂量组能降低家兔正常离体子宫平滑肌的
收缩频率和幅度，降低催产素所致子宫平滑肌剧烈收缩的幅
度，低剂量组和用药前比有统计学差异，高剂量组和用药前
及月月舒冲剂组比较均有统计学差异。④痛经巴布剂无明显
皮肤刺激征。
结论①通过动物实验证实中药痛经巴布剂能够治疗原
发性痛经。②中药痛经巴布剂治疗原发性痛经的作用机制与
其能抑制子宫平滑肌收缩(解痉作用)、降低PGEZ含量及镇
痛作用有关。③皮肤刺激试验初步说明痛经巴布剂是一个安
全的外用制剂。
Experimental Study on Anti-dysmenorrhea Effect of Tongjing Plaster
Objective To study the anti-dysmenorrhea effect and the skin irritation of Tongjing Plaster, which could be a conclusion that Tongjing Plaster can cure primary dysmenorrhea, and has no irritation reaction in skin. Methods (1)Twisting body reaction: SD female rats were divided into three groups randomly, vaseline group, ibuprofen group and Tongjing Plaster group .Intraperitoneal injected estradiol benzoate for 10 days. From the fifth days, each group received the medicine respectively for 6 days. At the eleventh day, intraperitoneal injected oxytocin, recorded twisting numbers of each rat within 30 minutes.(2)The effect on the concentration of PGE2 of rat models of dysmenorrhea: After (1) completed, measured the concentration of PGE2 in blood plasma and uterine tissue by radioimmunoassay(RIA).(3)The effect on extracorporeal uterine smooth muscle of rabbits: Female rabbits were intraperitoneal injected estradiol benzoate for 2 days. At the third day the rabbits were killed ,then measured the extent ,frequency
of the isolated uteri contractions, which influenced by yueyueshu pelletized granule ,high or dosage of Tongjing Plaster respectively .(4)The effect on extracorporeal uterine smooth muscle of rabbits which sensitized by oxytocin: the same method as (3), but the uteri sensitized by oxytocin. (5) Experimental study on skin irritation: hair -cut white rabbits were divided into complete skin group and injured skin group, each group received the
medicine respectively, then judged the results according to " Instructive principle for preclinic study of new Chinese drugs" .
Results (1)Tongjing Plaster evidently inhibited twisting body reaction of rat models of dysmenorrhea. (2) The content of PGEa in blood plasma and uterine tissue of Tongjing Plaster group was evidently under vacuity contrast group, the content in blood plasma of Tongjing Plaster had statistical significant comparing with ibuprofen ,but no statistical significant in uterine tissue.(3)Tongjing Plaster can reduce the frequency and extent of contraction in normal extracorporeal uterine smooth muscle, and reduce the extent of acutely contraction in uterine muscle sensitized by oxytocin. (4) No evidently irritation reaction occurred in either complete skin or injured skin.
Conclusion (1) Tongjing Plaster can cure primary dysmenorrhea. (2) Tongjing Plaster has effect on primary dysmenorrhea, the mechanism related to inhibiting contraction of isolated uteri both in normal and sensitized by oxytocin , reducing the content of PGE2 and the abirritation . (3)Tongjing Plaster has no irritation in skin, which initially proved Tongjing Plaster is a safe medcine.
引文
1 孙侠，高淑欣，马建智．纺织噪声对女工生殖机能的影响．河北医科大学学报，1998，19：93～95．
2 Hillen TI, Grbavac SL, Johnston PJ, et al J Adolesc Heath 1999, Jul. 25(1):40～5.
3 J Pediar, Primary dysmanorrhea in adolescent girls and treament with oral contraceptives Adolesc Gynecol, 2001 Feb. 14(1):3～8.
4 吕圭源，王一涛．中药新产品开发学．北京：人民卫生出版社，1997；345～346．
5 王北婴，李仪奎．中药新药研制开发技术与方法．上海：上海科学技术出版社，2001；700～707、567～568．
6 陈奇．中药药理研究方法学．北京：人民卫生出版社，1993；1110．
7 Steinmeyer J. pharmacological basis for the therapy of inflammation with nonsteroidal anti-inflammatory drugs.Arthritis Res. 2000, 2(5): 379～385.
8 徐增祥，史常旭．现代妇产科治疗学．北京：人民军医出版社，2002；229～230．
9 郑虎占，董泽宏，余靖．中药现代研究与应用．北京：学苑出版社，1998；第二卷．1816～1817．
10 苏竹一．近三年来中药丹参的药理学研究进展．中医药信息，1999，6：25．
11 魏莉，蔡贞贞，徐莲英．当归及其复方透皮吸收特性的研究．中国中药杂志，2000，25(1)：33～34．
12 蔡贞贞，魏莉，徐莲英．当归所含挥发油对阿魏酸透皮吸收的影响．中成药，1999，21(7)：334～335．
13 孙考祥，徐凯建，田辉凯，等．不同透皮促进剂对丹参帖膏离体透皮吸收的影响．中国药房，1998，9(2)：58～59．
14 马树人，钟天耕，于筛成，等．复合透皮吸收促进剂对丹参酮透皮作用的研究．中成药，2000，22(11)：749～752．
15 谢如嘉，章顺楠．氮酮对延胡索浸膏经皮给药的影响．中国药科大学学报，1995，26(2)：78～80．
16 沈琦，胡晋红，徐莲英．肉桂等3种挥发油对苯甲酸透皮吸收的影响．中国医院药学杂志，2001，21(4)：198．
17 董方言．现代中药新剂型新技术．北京：人民卫生出版社，2001：291．
18 Alber MK etal. Skin permeability:Dermatologic aspects of transderaml drug delivery. Am Heart J, 1984,108:200.
19 吴华振．中药巴布剂的研究进展．中药材，1999，22(2)：101．
20 孟李，王宁生．含药血清的制备方法研究．中药新药与临床药理，1999．9，10(5)：290～292．
21 党海珍，滕久祥，彭芝配，等．九气拈胶囊对痛经大鼠子宫组织内皮素和一氧化氮影响的实验研究．中国中医药科技，2001，8(3)：150～151．
22 吴涤，陈大方，刘学，等．CYP1A1Ⅱ-Hinc和GSTT1基因遗传多态性与原发性痛经关系．中华医学遗传学杂志，2001．2，18(1)：47～50．
23 吴涤，吕红霞，张秀清，等．PON1和PON2基因遗传多态性与
原发性痛经间关系．疾病控制杂志，2000．6．4(2)：129～131．
24 Treloar SA, Martin NG Health AC Longitudinal qenetic analysis of menstrual flow, pain and linitation in a sample of Australian twins Behaw Genet, 1998,28:107～116.
2 Hillen TI, Grbavac SL, Johnston PJ, et al J Adolesc Heath 1999, Jul. 25(1):40～5.
3 J Pediar, Primary dysmanorrhea in adolescent girls and treament with oral contraceptives Adolesc Gynecol, 2001 Feb. 14(1):3～8.
4 吕圭源，王一涛．中药新产品开发学．北京：人民卫生出版社，1997；345～346．
5 王北婴，李仪奎．中药新药研制开发技术与方法．上海：上海科学技术出版社，2001；700～707、567～568．
6 陈奇．中药药理研究方法学．北京：人民卫生出版社，1993；1110．
7 Steinmeyer J. pharmacological basis for the therapy of inflammation with nonsteroidal anti-inflammatory drugs.Arthritis Res. 2000, 2(5): 379～385.
8 徐增祥，史常旭．现代妇产科治疗学．北京：人民军医出版社，2002；229～230．
9 郑虎占，董泽宏，余靖．中药现代研究与应用．北京：学苑出版社，1998；第二卷．1816～1817．
10 苏竹一．近三年来中药丹参的药理学研究进展．中医药信息，1999，6：25．
11 魏莉，蔡贞贞，徐莲英．当归及其复方透皮吸收特性的研究．中国中药杂志，2000，25(1)：33～34．
12 蔡贞贞，魏莉，徐莲英．当归所含挥发油对阿魏酸透皮吸收的影响．中成药，1999，21(7)：334～335．
13 孙考祥，徐凯建，田辉凯，等．不同透皮促进剂对丹参帖膏离体透皮吸收的影响．中国药房，1998，9(2)：58～59．
14 马树人，钟天耕，于筛成，等．复合透皮吸收促进剂对丹参酮透皮作用的研究．中成药，2000，22(11)：749～752．
15 谢如嘉，章顺楠．氮酮对延胡索浸膏经皮给药的影响．中国药科大学学报，1995，26(2)：78～80．
16 沈琦，胡晋红，徐莲英．肉桂等3种挥发油对苯甲酸透皮吸收的影响．中国医院药学杂志，2001，21(4)：198．
17 董方言．现代中药新剂型新技术．北京：人民卫生出版社，2001：291．
18 Alber MK etal. Skin permeability:Dermatologic aspects of transderaml drug delivery. Am Heart J, 1984,108:200.
19 吴华振．中药巴布剂的研究进展．中药材，1999，22(2)：101．
20 孟李，王宁生．含药血清的制备方法研究．中药新药与临床药理，1999．9，10(5)：290～292．
21 党海珍，滕久祥，彭芝配，等．九气拈胶囊对痛经大鼠子宫组织内皮素和一氧化氮影响的实验研究．中国中医药科技，2001，8(3)：150～151．
22 吴涤，陈大方，刘学，等．CYP1A1Ⅱ-Hinc和GSTT1基因遗传多态性与原发性痛经关系．中华医学遗传学杂志，2001．2，18(1)：47～50．
23 吴涤，吕红霞，张秀清，等．PON1和PON2基因遗传多态性与
原发性痛经间关系．疾病控制杂志，2000．6．4(2)：129～131．
24 Treloar SA, Martin NG Health AC Longitudinal qenetic analysis of menstrual flow, pain and linitation in a sample of Australian twins Behaw Genet, 1998,28:107～116.