抗乳增生Ⅰ号治疗乳癖的主要药效的实验研究
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摘要
乳癖相当于现代医学的“乳房囊性增生病”和“乳房纤维腺瘤”。乳房囊性增生病多发于30-50岁妇女。其发病率占育龄妇女的47%,占全部乳腺疾病的75%。乳癖是临床最常见的乳房疾病,其发病率占乳腺疾病的首位。现代医学对本病的治疗无有效的治疗方法,主要是对症治疗。祖国医学认为乳腺增生病属“乳癖”范畴,多由情志内伤、肝郁痰结、气滞血瘀积聚乳房胃络所致。我的导师高鹏翔教授根据中医学理论,结合现代药理学研究,组成治疗肝郁痰凝、气血瘀滞型乳癖的有效方剂：抗乳增生Ⅰ号方。该方主要由赤芍、大贝、青皮、瓜蒌等组成,经过多年临床观察对肝郁痰凝型乳癖有较好的疗效。为了进一步探讨其作用机制,本实验根据中医基本理论,采用皮下注射雌二醇复制大鼠及家兔的乳腺增生模型,观察抗乳增生Ⅰ号对大鼠及家兔乳腺增生模型的影响。实验观察：1.对动物体态、外观的影响。2.乳房大体形态观察。3.乳腺组织病理切片观察。4.血清雌二醇含量测定。5.子宫病理切片观察。6.对大鼠棉球肉芽组织增生的影响、对角叉菜胶引起的足肿胀的影响、对免疫功能的影响、镇痛作用。
Kangruzengsheng I Hao is developed by Professor GaoPengxiang's owned experience who is the famous doctor of JiLin Province.The Preseription is including radix paeoniae rubrathe (unpeeled) root of common peony, Zhebeinine, Vatica astrotricha, Trichosanthes kirilowii Maxim,Wild Chrysanthemum,Curcuma longa,Khumbu, Prunella vulgaris, Bupleurum Root, algae, Sanleng etc.11 kinds of Chinese traditional medicine.It maily treats cyclomastopathy which is stagnation of QI due to depression of the liver.It is symptoms that swell, pain, nodules in the part of breast. Many years of clinical practice shows that it has significant effects.
Objective:
This research is to study pharmacological effects and interaction Mechanisms of Kangruzengsheng I Hao. Povide possible theoretical and experimental foundation for the decoction's clinic trial and application.
Methods:
The pharmacodynamic action experiments are including
1. Effect of Kangruzengsheng I Hao on the experimental studies on experimental cyclomastopathy.
1. Effect of Kangruzengsheng I Hao on the experimental studies on rat cyclomastopathy.
Drugs or distilled water were given to sixty operated rats successively, all rats were killed 1 hour after the last administration. Measure levels of serum estradiol. Observe histopathologic changes of the second pairs of breasts, ovaries and uterus under the light microscope.
1.2 Effect of Kangruzengsheng I Hao on the experimental studies on rabbit
Cyclomastopathy. Drugs or distilled water were given to female rabbits successively, all rats were killed 1 hour after the last administration. Measure levels of serum estradiol. Observe histopathologic changes of the second pairs of breasts, ovaries, uterus under light microscope.
2. Effect of Kangruzengsheng I Hao on the experimental studies on experimental inflammation.
2.1. Effect on SN-263 cryptopodia of rats,which is to inject 0.1ml of 1% SN-263 in right rear foot aponeurosis palmaris of rats.Measure the right rear foot aponeurosis once an hour,total six hours. The difference circumference of foot vola between right-left gambrel is cryptopodia level.
2.2. Effect on cotton pellet granuloma of rats, which is to put the rat to death, peel off the granuloma and dry I tinto hot oven under60℃, then weight it.
3. Effect on hemorheology of rats.Sixty operated rats were randomly divided into 6 groups with 10 animals in each group.Each group is successive administrated or given homo-volume normal saline one time per day for ten days. Inject adrenalin twice 0.08ml per 100g weight the NO.1 to NO.5 groups by hypodermic injection and immerse rats into ice water for 5m. Feed withdrawal prior to slaughter then anesthetize all animal with 1.5%amobarbital sodium 35mg/kg by intraperitoneal injection. Take blood of aorta abdominalis and detecte hemorheology.
4. Effect on immune function:
4.1 Effect of Kangruzengsheng I Hao on endothelial system dysphagocytosis of mouse, which is to inject ink in the trail of mouse and take 40ul blood into 4ml distilled water test tube from orbital vein in 2m and 15m later. Measure the OD, calculate the rate of carbon particles clearance in blood in minute, and weight the spleen and liver to verify K value.
4.2 Effect on phagocytic function of mouse peritoneal macrophage,which is to inject lml of 5%chicken red blood cell then kill mouse after 8 hours. Draw 1ml intraperitoneal perfusion,observe them and calculate the phagocytic percentage.
5. Effect on writhing response of mouse caused by acetic acid, which is to inject 0.6% acetic acid liquid as 0.1ml/10g according to weight.Observe the times and of writhing response in ten minutes.
Results:
The experiment result indicates that:diameter and height of breasts of rats increased significantly; blood estradiol level of rats rised up significantly; small breast dusts and acini of rats occur obvious histopathological changes, they can be called typical experimental animal models. Kangruzengsheng I Hao has different degree of inhibition to these indicators of breast hyperplasia. It has inhibiting effect on carrageenin cryptopodia of rats and cotton pellet granuloma of rats. It can improve immune function of mouse. Also it can reduce whole blood viscosity, plasma viscosity and hematocrit etc.. Besides,it has obvious analgesic action.
Conclusion:
Kangruzengsheng I Hao has obvious effect on reducing breast enlargement breast diameter, estrogen level, parenchymal cells and structural changes. It has pharmacological activity in many aspects including:modify hemorheology of experimental animal,improve immune function, anti-inflammation and antinociceptive effects. All that is coincide with clinical observation of efficacy.
We believe that Kangruzengsheng I Hao is effective drug treatment cyclomastopathy.
Kangruzengsheng I Hao is developed by Professor GaoPengxiang's owned experience who is the famous doctor of JiLin Province.The Preseription is including radix paeoniae rubrathe (unpeeled) root of common peony, Zhebeinine, Vatica astrotricha, Trichosanthes kirilowii Maxim,Wild Chrysanthemum,Curcuma longa,Khumbu, Prunella vulgaris, Bupleurum Root, algae, Sanleng etc.11 kinds of Chinese traditional medicine.It maily treats cyclomastopathy which is stagnation of QI due to depression of the liver.It is symptoms that swell, pain, nodules in the part of breast. Many years of clinical practice shows that it has significant effects.
Objective:
This research is to study pharmacological effects and interaction Mechanisms of Kangruzengsheng I Hao. Povide possible theoretical and experimental foundation for the decoction's clinic trial and application.
Methods:
The pharmacodynamic action experiments are including
1. Effect of Kangruzengsheng I Hao on the experimental studies on experimental cyclomastopathy.
1. Effect of Kangruzengsheng I Hao on the experimental studies on rat cyclomastopathy.
Drugs or distilled water were given to sixty operated rats successively, all rats were killed 1 hour after the last administration. Measure levels of serum estradiol. Observe histopathologic changes of the second pairs of breasts, ovaries and uterus under the light microscope.
1.2 Effect of Kangruzengsheng I Hao on the experimental studies on rabbit
Cyclomastopathy. Drugs or distilled water were given to female rabbits successively, all rats were killed 1 hour after the last administration. Measure levels of serum estradiol. Observe histopathologic changes of the second pairs of breasts, ovaries, uterus under light microscope.
2. Effect of Kangruzengsheng I Hao on the experimental studies on experimental inflammation.
2.1. Effect on SN-263 cryptopodia of rats,which is to inject 0.1ml of 1% SN-263 in right rear foot aponeurosis palmaris of rats.Measure the right rear foot aponeurosis once an hour,total six hours. The difference circumference of foot vola between right-left gambrel is cryptopodia level.
2.2. Effect on cotton pellet granuloma of rats, which is to put the rat to death, peel off the granuloma and dry I tinto hot oven under60℃, then weight it.
3. Effect on hemorheology of rats.Sixty operated rats were randomly divided into 6 groups with 10 animals in each group.Each group is successive administrated or given homo-volume normal saline one time per day for ten days. Inject adrenalin twice 0.08ml per 100g weight the NO.1 to NO.5 groups by hypodermic injection and immerse rats into ice water for 5m. Feed withdrawal prior to slaughter then anesthetize all animal with 1.5%amobarbital sodium 35mg/kg by intraperitoneal injection. Take blood of aorta abdominalis and detecte hemorheology.
4. Effect on immune function:
4.1 Effect of Kangruzengsheng I Hao on endothelial system dysphagocytosis of mouse, which is to inject ink in the trail of mouse and take 40ul blood into 4ml distilled water test tube from orbital vein in 2m and 15m later. Measure the OD, calculate the rate of carbon particles clearance in blood in minute, and weight the spleen and liver to verify K value.
4.2 Effect on phagocytic function of mouse peritoneal macrophage,which is to inject lml of 5%chicken red blood cell then kill mouse after 8 hours. Draw 1ml intraperitoneal perfusion,observe them and calculate the phagocytic percentage.
5. Effect on writhing response of mouse caused by acetic acid, which is to inject 0.6% acetic acid liquid as 0.1ml/10g according to weight.Observe the times and of writhing response in ten minutes.
Results:
The experiment result indicates that:diameter and height of breasts of rats increased significantly; blood estradiol level of rats rised up significantly; small breast dusts and acini of rats occur obvious histopathological changes, they can be called typical experimental animal models. Kangruzengsheng I Hao has different degree of inhibition to these indicators of breast hyperplasia. It has inhibiting effect on carrageenin cryptopodia of rats and cotton pellet granuloma of rats. It can improve immune function of mouse. Also it can reduce whole blood viscosity, plasma viscosity and hematocrit etc.. Besides,it has obvious analgesic action.
Conclusion:
Kangruzengsheng I Hao has obvious effect on reducing breast enlargement breast diameter, estrogen level, parenchymal cells and structural changes. It has pharmacological activity in many aspects including:modify hemorheology of experimental animal,improve immune function, anti-inflammation and antinociceptive effects. All that is coincide with clinical observation of efficacy.
We believe that Kangruzengsheng I Hao is effective drug treatment cyclomastopathy.
引文
[1]饶金才等,乳腺增生病动物模型的复制及病理类型,中国病理生理杂志,1992;8(6)：671
[2]陈奇主编,中药药理研究方法学,北京,人民卫生出版社,566
[3]杨国汉,止痛消结膏对乳腺增生动物模型的作用,湖南中医学院学报,1991；11(2)：44
[4]安丽、毛肖三等,乳腺增生的中药治疗及实验研究,新中医,1997；29(4)：13
[5]卫舰萍,浅谈乳腺增生病的辨证施治Asia-Pacific Traditional Medicine Vol.5 No.6Jun2009
[6]樊凤英.浅谈冲任失调与乳腺增生病.南京中医药大学学报,2002,18(5)：266-267
[7]周凯,辛红.陆德铭治疗乳腺增生病经验拾粹.山西中医,2004,4(20)：9-10
[8]张定学.乳消平胶囊治疗乳腺增生500例.中国中医药信息杂志,2001,8(9)：65
[9]郭云岭.散结止痛汤治疗乳腺增生35例临床研究.现代中西医结合,2004,4(13)：889-990
[10]邓国华,杨清芬.血竭胶囊治疗乳腺增生病32例疗效观察.现代医院,2004,4(4)：64
[11]杨晓翡.乳腺增生患者情志变化与肝郁的关系探讨.中华新医学,2003,4(5)：437
[12]徐先祥,夏伦祝,高家荣,等.黄芪总苷和赤芍总苷协同抗血小板作用研究[J].中药材,2002,25(9)：653-65
[13]朱剑华,王安莲.赤芍水溶性提取液的诱变性和抗诱变性研究[J].安徽预防医学杂志,1998,4(1)：49--51.
[14]孙继红中药内服外敷治疗乳腺增生40例陕西中医[J],2001.22(3)：146-146
[15]王丹青、董晓霞、 李巧玲乳腺增生胶囊的制备与临床应用陕西中医[J]2001.22(12)：760-760
[16]李兴泰、张家俊、陈文为等补气与理气中药对慢性缺氧小鼠能量代谢的作用[J]北京中医药大学学报1992,22(3)：32-35
[17]凌红 瓜蒌、心得安对血小板体外集聚和TXA2合成的影响[J]湖北医学院学报,1988,9(2)：138
[18]宋海波,李建香,杨来启,等.瓜蒌散加味治疗乳腺囊性增生136例[J]陕西中医,2001,22(3)：145
[19]秦林,高伟良瓜蒌对子宫颈癌细胞和巨噬细胞的影响[J] 山东中医学院学报,1995,19(6)：414
[20]王志刚,任爱农,许立,等.野菊花抗炎和免疫作用的实验研究[J].中国中医药科技,2000,7(2)：92
[21]张驻艳,张磊,金涌,等.野菊花总黄酮抗炎作用厦部分机制[J]安徽医科大学学报.2005.40(5)：加5.
[22]程文明淳倥,胡成穆野菊花提取物的抗炎及免疫调节作用[J]中国药理通讯,2005,22(3)：49
[23]刘晓斌.高燕.北柴胡提取组分对小鼠淋巴细胞活性的影响[J]细胞与分子免疫学杂志.2002.18(6)：600-600
[24]马春玲、张西强南柴胡对小鼠免疫功能影响的实验研究[J]临沂医专学报。1999.21(1)：11-11
[25]张亮.胡海宝。南柴胡多糖分离与组成的初步研究[J]中草药。2000.31(9)：647-647
[26]Yen Ming-Hong Lin Chun-Ching.immunomdulatory effect of saikosaponin derivatives and the root extract of Bupleurum Kaoiin mice[J] Phytother. Res. 1995.9(5):351-358
[27]宋景贵肖正明柴胡提取物对人肝癌细胞和小鼠S-180肉瘤的抑制作用[J].山东中医药大学学报,2001.25(4),299-299
[28]邓英军.三棱不同提取物镇痛及抗凝血作用研究.时珍国医国药,1999,16(2)：1-3.
[29]邱鲁耍,等.三棱总黄酮镇痛作用研究.时珍国医国药,2000,11(4)：291-292.
[2]陈奇主编,中药药理研究方法学,北京,人民卫生出版社,566
[3]杨国汉,止痛消结膏对乳腺增生动物模型的作用,湖南中医学院学报,1991；11(2)：44
[4]安丽、毛肖三等,乳腺增生的中药治疗及实验研究,新中医,1997；29(4)：13
[5]卫舰萍,浅谈乳腺增生病的辨证施治Asia-Pacific Traditional Medicine Vol.5 No.6Jun2009
[6]樊凤英.浅谈冲任失调与乳腺增生病.南京中医药大学学报,2002,18(5)：266-267
[7]周凯,辛红.陆德铭治疗乳腺增生病经验拾粹.山西中医,2004,4(20)：9-10
[8]张定学.乳消平胶囊治疗乳腺增生500例.中国中医药信息杂志,2001,8(9)：65
[9]郭云岭.散结止痛汤治疗乳腺增生35例临床研究.现代中西医结合,2004,4(13)：889-990
[10]邓国华,杨清芬.血竭胶囊治疗乳腺增生病32例疗效观察.现代医院,2004,4(4)：64
[11]杨晓翡.乳腺增生患者情志变化与肝郁的关系探讨.中华新医学,2003,4(5)：437
[12]徐先祥,夏伦祝,高家荣,等.黄芪总苷和赤芍总苷协同抗血小板作用研究[J].中药材,2002,25(9)：653-65
[13]朱剑华,王安莲.赤芍水溶性提取液的诱变性和抗诱变性研究[J].安徽预防医学杂志,1998,4(1)：49--51.
[14]孙继红中药内服外敷治疗乳腺增生40例陕西中医[J],2001.22(3)：146-146
[15]王丹青、董晓霞、 李巧玲乳腺增生胶囊的制备与临床应用陕西中医[J]2001.22(12)：760-760
[16]李兴泰、张家俊、陈文为等补气与理气中药对慢性缺氧小鼠能量代谢的作用[J]北京中医药大学学报1992,22(3)：32-35
[17]凌红 瓜蒌、心得安对血小板体外集聚和TXA2合成的影响[J]湖北医学院学报,1988,9(2)：138
[18]宋海波,李建香,杨来启,等.瓜蒌散加味治疗乳腺囊性增生136例[J]陕西中医,2001,22(3)：145
[19]秦林,高伟良瓜蒌对子宫颈癌细胞和巨噬细胞的影响[J] 山东中医学院学报,1995,19(6)：414
[20]王志刚,任爱农,许立,等.野菊花抗炎和免疫作用的实验研究[J].中国中医药科技,2000,7(2)：92
[21]张驻艳,张磊,金涌,等.野菊花总黄酮抗炎作用厦部分机制[J]安徽医科大学学报.2005.40(5)：加5.
[22]程文明淳倥,胡成穆野菊花提取物的抗炎及免疫调节作用[J]中国药理通讯,2005,22(3)：49
[23]刘晓斌.高燕.北柴胡提取组分对小鼠淋巴细胞活性的影响[J]细胞与分子免疫学杂志.2002.18(6)：600-600
[24]马春玲、张西强南柴胡对小鼠免疫功能影响的实验研究[J]临沂医专学报。1999.21(1)：11-11
[25]张亮.胡海宝。南柴胡多糖分离与组成的初步研究[J]中草药。2000.31(9)：647-647
[26]Yen Ming-Hong Lin Chun-Ching.immunomdulatory effect of saikosaponin derivatives and the root extract of Bupleurum Kaoiin mice[J] Phytother. Res. 1995.9(5):351-358
[27]宋景贵肖正明柴胡提取物对人肝癌细胞和小鼠S-180肉瘤的抑制作用[J].山东中医药大学学报,2001.25(4),299-299
[28]邓英军.三棱不同提取物镇痛及抗凝血作用研究.时珍国医国药,1999,16(2)：1-3.
[29]邱鲁耍,等.三棱总黄酮镇痛作用研究.时珍国医国药,2000,11(4)：291-292.