不同检测方法在药物安全性评价试验中效果比较  

Comparison of different detection methods in drug safety evaluation test

作　　者：张成梅[1,2] 史艳秋[1] 赵秀兰[2] 武传涛[1] 张翠丽[2] 陈晶晶[2] 李春令[3] 谢克勤[2] 

机构地区：[1]山东大学实验动物中心,济南250012 [2]山东大学公共卫生学院毒理学研究所,济南250012 [3]山东省医疗器械产品质量检验中心,济南250101

出　　处：《山东大学学报（医学版）》2013年第11期51-55,共5页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81072569)

摘　　要：目的比较酶组化法、生化法及病理检测法在低分子量褐藻多糖硫酸酯(LMWF)安评试验中药物毒性反应的敏感性。方法 16只Beagle犬,雌雄各半,按体质量随机分为对照组,LMWF低、中、高[200、800、3 000 mg/(kg·d)]剂量组,每组4只,灌胃给药13周。检测第1次给药前及末次给药后的动物血清生化指标。末次给药后,麻醉处死动物取肝脏,在肝脏相同位置取1 cm3大小组织,速冻、切片及染色,进行酶组织化学检测。另取肝脏组织用4%中性甲醛溶液固定,石蜡包埋切片,HE染色,光学显微镜检查。结果给药前和给药结束后,LMWF各给药组动物的血清生化指标与Veh组比较差异无统计学意义(P>0.05);光学显微镜观察,各给药组动物肝脏的组织形态并未发现明显病变;肝脏ATPase和SDH无论是定性观察还是定量分析,LMWF高剂量组给药酶活性下降明显,与对照组比较差异有统计学意义(P<0.05)。结论酶组化法对毒物的敏感性要高于血清生化法及病理学法。Objective To elucidate the effects of serum biochemistry, pathological detection and enzymatic histochemistry in LMWF regarding drug safety evaluation. Methods 16 Beagle dogs（8 males and 8 females）were randomly divided into 4 groups（Group Veh, Group 200mg/kg/d, Group 800mg/kg/d, and Group 3000mg/kg/d of LMWF, n=4 in each group）according to the body weight. They were fed with stomach lavaging once per day and 6 day per week for 13 weeks. Serum biochemical index were tested prior to the first LMWF treatment and after the last treatment. Liver was taken and frozen in liquid nitrogen, sectioned, stained, and carried on the enzyme histochemical detection. The liver was fixed by 4% neutral formaldehyde, paraffin-embedded, HE stained, and detected by the microscopy. Results Compared with Veh group, no obvious deviation of serum biochemistry index appeared in LMWF treated groups （P〉0.05）; no evident pathological changes was found in LMWF treated liver histomorphology by microscopy observation. Both adenosine triphosphatase（ATPase） and succinate dehydrogenase（SDH） activities detected by liver qualitative observation and quantitative analysis, significantly decreased, compared with the Veh group（P〈0.05）. Conclusion LMWF 3000mg/kg/d dose could reduce ATPase and SDH activities, indicating that the liver mitochondrial function may be impacted, also shows that enzyme staining method is more sensitive than biochemical and pathological Methods.

关 键 词：肝 毒性 酶 生化 病理 BEAGLE犬 

分 类 号：R996.3[医药卫生—毒理学]