甘草调和大黄“泻下攻积”作用的量-毒-效关系研究
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摘要
该文研究甘草对不同剂量大黄"泻下攻积"效应及毒副作用的调和之性。将108只ICR小鼠分为空白组,模型组,阳性药物组,低、中、高剂量大黄组,低、中、高剂量大黄甘草汤组,以盐酸洛哌丁胺连续给药6 d复制小鼠便秘模型后,各组分别给予乳果糖、不同剂量大黄及大黄甘草汤水提液14 d。给药结束后比较各组小鼠排便特征,血液生化,肝、肾、结肠病理学改变情况,并基于因子分析给出的客观权重,采用多指标评分法综合分析大黄-甘草配伍前后的量-毒-效关系。通过因子分析提取了2个公因子,分别代表效应和毒性。结果显示,大黄在《中国药典》高限1/2,2,8倍剂量下均能产生较好的泻下效果,增加小鼠排便量及肠道推进率,减少口肛传输时间,增加粪便含水量;与甘草配伍能缓和其泻下作用,在《中国药典》高限的1/2剂量下尤为明显。而《中国药典》高限2,8倍剂量下大黄表现出明显的肝脏及结肠毒性,能够使小鼠ALT,AST升高,肝细胞空泡变性,结肠系数增加;与甘草配伍能显著降低其毒性。结果表明甘草对大黄具有"调和"作用,一方面能够缓和大黄的"泻下攻积"之效,另一方面则能减弱大黄峻猛之性导致的肝肠毒性。
The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.
The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.
引文
[1]宋美珍,俞捷,包·照日格图.浅谈中药配伍减毒及现代研究[J].中药与临床,2012,3(2):51.
[2]翁小刚,李玉洁,陈颖,等.倡议树立方剂“主效应”研究的新思路——对中药复方作用机制与配伍机制研究的新思考[J].中国中药杂志,2018,43(18):3782.
[3]段金廒,范欣生,宿树兰,等.中药及方剂量效关系的研究进展与思考[J].南京中医药大学学报,2009,25(4):241.
[4]范欣生,段金廒,王中越,等.中药量效关系特征问题的探讨[J].中华中医药杂志,2009,24(3):270.
[5]高学敏.中药学[M].北京:中国中医药出版社,2007:157.
[6]杨柏灿,潘颖宜.甘草“调和”的影响因素探析[J].中成药,2013,35(1):154.
[7]苏彬.配伍甘草对大黄泻下作用影响的研究进展[J].中国中药杂志,2015,40(4):577.
[8]邱建烽.大黄甘草汤临床应用体会[J].实用中医药杂志,2016,32(6):616.
[9]黄小丽,陈琳,陈晨,等. 3种便秘模型的比较研究[J].四川动物,2015,34(1):111.
[10]占煜,申旭龙,徐红,等.大黄对洛哌丁胺便秘模型大鼠结肠水通道蛋白3表达及肠动力的作用研究[J].中华中医药学刊,2016,34(10):2315.
[11]李承明.不同炮制和煎煮时间对大黄沉降药性的影响研究[J].中国现代药物应用,2015,9(4):240.
[12]杨裕忠,王新芳.大承气汤大黄后下时间对阳明腑实证的临床疗效观察[J].世界中医药,2014,9(7):904.
[13]周学平,周玲玲,王旭.基于“异类相制”理论探讨中药复方的配伍减毒作用[J].中医杂志,2013(4):271.
[14]王亦君,冯舒涵,程锦堂,等.大黄蒽醌类化学成分和药理作用研究进展[J].中国实验方剂学杂志,2018,24(13):227.
[15]罗培,徐象珍,谭正怀,等.大黄游离蒽醌致泻作用机制研究[J].中药药理与临床,2013,29(3):88.
[16]甄权撰,尚志钧.药性论——药性趋向分类论[M].合肥:安徽科学技术出版社,2006:153.
[17]杨柏灿,潘颖宜.甘草在调和药效中的应用[J].中药与临床,2012,3(2):45.
[2]翁小刚,李玉洁,陈颖,等.倡议树立方剂“主效应”研究的新思路——对中药复方作用机制与配伍机制研究的新思考[J].中国中药杂志,2018,43(18):3782.
[3]段金廒,范欣生,宿树兰,等.中药及方剂量效关系的研究进展与思考[J].南京中医药大学学报,2009,25(4):241.
[4]范欣生,段金廒,王中越,等.中药量效关系特征问题的探讨[J].中华中医药杂志,2009,24(3):270.
[5]高学敏.中药学[M].北京:中国中医药出版社,2007:157.
[6]杨柏灿,潘颖宜.甘草“调和”的影响因素探析[J].中成药,2013,35(1):154.
[7]苏彬.配伍甘草对大黄泻下作用影响的研究进展[J].中国中药杂志,2015,40(4):577.
[8]邱建烽.大黄甘草汤临床应用体会[J].实用中医药杂志,2016,32(6):616.
[9]黄小丽,陈琳,陈晨,等. 3种便秘模型的比较研究[J].四川动物,2015,34(1):111.
[10]占煜,申旭龙,徐红,等.大黄对洛哌丁胺便秘模型大鼠结肠水通道蛋白3表达及肠动力的作用研究[J].中华中医药学刊,2016,34(10):2315.
[11]李承明.不同炮制和煎煮时间对大黄沉降药性的影响研究[J].中国现代药物应用,2015,9(4):240.
[12]杨裕忠,王新芳.大承气汤大黄后下时间对阳明腑实证的临床疗效观察[J].世界中医药,2014,9(7):904.
[13]周学平,周玲玲,王旭.基于“异类相制”理论探讨中药复方的配伍减毒作用[J].中医杂志,2013(4):271.
[14]王亦君,冯舒涵,程锦堂,等.大黄蒽醌类化学成分和药理作用研究进展[J].中国实验方剂学杂志,2018,24(13):227.
[15]罗培,徐象珍,谭正怀,等.大黄游离蒽醌致泻作用机制研究[J].中药药理与临床,2013,29(3):88.
[16]甄权撰,尚志钧.药性论——药性趋向分类论[M].合肥:安徽科学技术出版社,2006:153.
[17]杨柏灿,潘颖宜.甘草在调和药效中的应用[J].中药与临床,2012,3(2):45.