纤维蛋白封闭剂对SD大鼠连续腹腔注射给药14天的毒性研究  

Repeat-dose toxicity study of fibrin sealant in SD rats

作　　者：戴小宇[1] 朱海[1] 张晓冬[1] 张晓芳[1] 宗英[1] 戴益民[1] 张淑英[1] 袁伯俊[1] 陆国才[1] 

机构地区：[1]第二军医大学药物安全性评价中心,上海200433

出　　处：《药学实践杂志》2015年第3期231-234,共4页Journal of Pharmaceutical Practice

基　　金："重大新药创制"科技重大专项(2014ZX09J14106);上海市公共卫生重点实验室建设计划(12GWZX0501);上海市自然科学基金(13ZR1449400)

摘　　要：目的：评价SD大鼠连续腹腔注射纤维蛋白封闭剂的安全性。方法 SD大鼠雌雄分别按体质量随机分4组，即空白对照组、纤维蛋白封闭剂低剂量组、中剂量组和高剂量组，每组20只，雌雄各半。3个给药组的给药剂量分别为85.5、171．0和342．0 mg／kg ，每天腹腔注射给药，连续14 d ，恢复期28 d ，进行一般症状、血液学、血液生化和病理组织学等指标检测。结果与空白对照组相比，纤维蛋白封闭剂中、高剂量组大鼠第14天的白细胞计数显著升高，纤维蛋白原显著降低，中、高剂量组大鼠脾脏的脏器重量有增加趋势。组织病理学检查发现部分高剂量动物腹腔出现残留药物引起的纤维肉芽组织包裹。上述变化指标在恢复期结束时基本可恢复。结论大鼠腹腔注射纤维蛋白封闭剂85.5∽342．0 mg／kg ，安全剂量为85.5 mg／kg ，毒性剂量为171．0 mg／kg。毒性靶系统或靶部位为血液系统、免疫系统和给药局部，毒性作用可逆。Objective To evaluate the safety of fibrin sealant （FS） intraperitoneal injection in SD rats .Methods 80 male and female SD rats were randomly divided into four groups （0 ,85.5 ,171 .0 ,342 .0 mg/kg） by body weight .All rats were in-traperitoneally injected with vehicle or FS daily for 14 days followed by a 28-day recovery period .The clinical signs ,hematolog-ical and biochemical indices were measured .The pathology were observed .Results Increase of white blood cell count （WBC） and decrease of fibrinogen （FIB） in d 14 were found in 171 .0 mg/kg and 342 .0 mg/kg dosage groups .Furthermore ,the tend-ency of weight increase of spleen were found in 171 .0 mg/kg and 342 .0 mg/kg dosage groups .Pathological exams of peritoneal cavity found that there were granulation tissues containing FS in some of the rats in 342 .0 mg/kg group .All of these changes got reversed after the recovery period .Conclusion The safety dose in this study is considered to be 85.5 mg/kg ,and the toxic-ity dose is 171 .0 mg/kg .The target toxicity systems or site of FS in SD rats are hematological system ,immune system and in-jection site .The toxic effects of FS are reversible .

关 键 词：纤维蛋白封闭剂 SD大鼠 重复给药毒性 临床前安全性 

分 类 号：R965[医药卫生—药理学]