尖吻蝮蛇毒无出血活性纤溶酶对大鼠的长期毒性试验  

Long-term toxicity of non-hemorrhagic fibrinolytic enzyme from Agkistrodon acutus in rats

作　　者：彭均华[1] 黎渊弘[2] 侯小琼[3] 雷丹青[4] 黎肇炎[4] 

机构地区：[1]广西医科大学病理生理学教研室,南宁530021 [2]广西医科大学第一附属医院药剂科,南宁530021 [3]广西医科大学微生物学与免疫学教研室,南宁530021 [4]广西医科大学蛇毒研究所,南宁530021

出　　处：《中国新药杂志》2008年第11期939-941,共3页Chinese Journal of New Drugs

基　　金：广西科学研究与技术开发资助项目(桂科攻0143050)

摘　　要：目的:研究无出血活性纤溶酶(Non-hemorrhagic fibrinolytic enzyme,NHFLE)对大鼠的长期毒性,评价其安全性。方法:健康Wistar大鼠随机分为低、中、高剂量(2.25,4.5,9.0 mg·kg^(-1)·d^(-1))组及生理氯化钠注射液对照组,每组24只。尾静脉注射给药,每周给药7 d,连续给药4周,给药容积为10 mL·kg^(-1)。停药后24 h每组处死12只动物,余下动物继续观察2周后活杀检查。观察动物一般性状、体重、饮食等,检测血液学、凝血、血液生化、脏器系数及组织病理学改变。结果:NHFLE高剂量组大鼠在4周给药期出现多动、烦躁不安、轻微腹泻以及体重增长缓慢,以上改变在停药后恢复正常,其余动物各项检查未见异常。结论:NHFLE毒性较低。Objective： To evaluate the safety of non-hemorrhagic fibrinolytic enzyme （NHFLE） from Agkistrodon acutus by long-term toxicity tests in rats. Methods： Healthy Wistar rats were randomly divided into three groups （ n = 24 each）, and received injection of NHFLE （2.25,4.5,9.0 mg· kg - 1. d - 1 ） for 4 weeks through the vena caudalis. Saline was injected as control （n = 24）. The administration volume of NHFLE or saline was 10 mL· kg-1 Half of the rats in each group （ n = 12） were sacrificed 24 h after the last dosing, and other rats were sacrificed after 2-week recovery observation. The physical status, body weight, food and drink conditions were observed, and the changes in hematology, blood clotting, biochemistry parameters, organ index and histopathology were determined. Results： During the 4 weeks of intravenous administration, the rats treated with 9.0 mg·kg-1· d-1 showed more activity, dysphoria, slight diarrhea and less weight increase than the control group, and these changes were recovered within 2-week withdrawal. No significant abnormality was found in other groups. Conclusion： NHFLE toxicity is low in long-term tests.

关 键 词：蛇毒 尖吻蝮蛇 纤溶酶 长期毒性试验 

分 类 号：R973.2[医药卫生—药品] R994.22[医药卫生—药学]