甘草调和大黄“泻下攻积”作用的量-毒-效关系研究

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。

Dose-toxicity-effect relationship between licorice combined with rhubarb in purgation

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.