药物安全评价中试验用犬的选择相关性研究

目的分析比较实验犬灌胃前后的心电图、血常规、血清生化指标的变化。方法选用武汉本地杂交犬与产自上海、广东的Beagle犬,检测灌胃前后心电图、血液学常规、血清生化指标。结果心电图:与广东Beagle犬比较,灌胃前武汉本地杂交犬,心率、QRS间期明显低,P-R、QT间期明显高,灌胃给水4周后,P-R明显高,QRS、QT间期明显低或低;与上海产Beagle犬比较,心率、P-R、QT、QRS间期明显高,灌胃给水4周后,QT间期明显低。血液学常规:与上海Beagle比较,杂交犬灌胃前血红蛋白含量、红细胞数、中性白细胞数明显高,灌胃给水4周后,白细胞数明显低;与广东犬比较,灌胃前血红蛋白含量、红细胞数明显高,灌胃给水4周后,红细胞数明显高。血液生化指标:与上海产Beagle犬比较,武汉本地杂交犬在灌胃前ALB、Cre、GLU、ALT、AST明显高或高,ALP、BUN、CHOL明显低;与广东Beagle比较,灌胃前AST、TP、ALB、GLU明显高,而ALP明显低。灌胃给水四周后差异趋势与灌胃前检测结果具备一定的相似性。结论在药物安全性评价中应普及使用Beagle犬,使用杂交犬必须选用按封闭群生产方式的育成犬作为实验用犬,且每个剂量组的样本数宜相对较多以便筛选。

A Study on Selection of Experimental Dogs in Safety Evaluation for Drugs

Objective To investigate relevant characteristics of experimental dogs and provide the data for selection of experimental dogs in safety evaluation for drugs.Methods 28 Beagles from Guangdong,20 Beagles from Shanghai,and 24 hybrid dogs from Wuhan suburb were used in this series.Their electrocardiogram and blood routine examination were done,and their blood biochemical indexes were determined before and after oral administration of H_2O(2 mL/kg).Results Heart rate was faster and QRS and QT intervals were more extended in Wuhan hybrid than in Guangdong Beagles before the experiment.Haemoglobin level,erythrocyte and neutrocyte count were higher in Wuhan hybrid than in Shanghai Beagles before oral administration of H_2O and leucocyte count was lower in Wuhan hybrid than in Shanghai Beagles after oral administration of H_2O for 4 weeks.Haemoglobin level and erythrocyte count were higher in Wuhan hybrid than in Guangdong beagles before oral administration of H_2O,and erythrocyte count was higher in Wuhan hybrid than in Guangdong beagles after oral administration of H_2O for 4 weeks.ALB,Cre,GLU,ALT,and AST were significantly higher and ALP,BUN,and CHOL were lower in Wuhan hybrid than in Shanghai Beagles.AST,TP,ALB,and GLU were significantly higher and ALP was lower in Wuhan hybrid than in Guangdong Beagles before oral administration of H_2O.Conclusion Beagle should be popularly used in safety evaluation for drugs.