复方尼尔雌醇片急性和长期毒性的动物实验研究  

Acute and chronic toxicity of compound nylestriol tablet in exper imental animals

作　　者：廖二元[1] 戴如春[1] 罗湘杭[1] 廖慧娟[1] 伍贤平[1] 李焕德[2] 程泽龙[2] 孙瑞元[3] 刘锡玖 

机构地区：[1]中南大学湘雅二医院代谢内分泌研究所,长沙410011 [2]湘雅二医院药剂科 [3]皖南医学院药理研究所

出　　处：《中国骨质疏松杂志》2003年第2期155-161,共7页Chinese Journal of Osteoporosis

基　　金：国家"九五"攻关项目 ( 96 90 6 0 5 0 5);国家自然科学基金项目 ( 39970 34 7);国家"十五"攻关项目 ( 2 0 0 1BA70 2B0 3);湖南省社会发展科研计划 ( 99SSY10 0 9 10 )

摘　　要：目的　观察复方尼尔雌醇片 (CNT)的急性和长期毒性反应。方法　本研究分为急性和长期毒性试验两部分 ,包括 3种动物的 5项独立试验。用昆明种小鼠和杂种家犬分别对CNT的LD50 、心血管系统、呼吸系统、神经系统等进行了急性毒性试验。实验结束后 ,尸解全部动物 ,进行系统病理和主要器官的组织病理检查。在长期毒性试验中 ,对SD大鼠和杂种家犬分别进行了 6个月的观察 ,于实验后 2月 (家犬 )或 4月 (SD大鼠 )、6月和停药后 2周 (SD大鼠 )或 3周 (家犬 )采血或处死动物 ,测定血液学、血生化学、尿生化指标和肝、肾功能指标。取各器官进行组织病理学检查。结果　 (1 )CNT的LD50 为 66 6mg/kg(腹腔注射 ) ,相当于临床用量的 681倍。最大耐受量为 32 5mg/kg(灌胃法 ) ,相当于临床用量的 3 32 5倍。 (2 )高于临床用量 3倍和 9倍剂量的CNT对小鼠无明显急性神经毒性、心血管毒性或呼吸系统毒性 ,亦未发现对其他主要脏器有何急性毒性反应。 (3)在观察 6个月期间内 ,高于临床用量的 36 7和 1 4 4倍的CNT剂量对SD大鼠和家犬无明显长期毒性反应。但SD大鼠在给予CNT或尼尔雌醇后 ,摄食减少、体重下降 (与对照组比较 ,P <0 0 0 1 ) ,同时发现血浆红细胞计数和血红蛋白降低 (与对照组比较 ,P <0 0 5～P <0 0 0 1 ) 。Objective To observe the acute and chronic tox ic ity in experimental animals treated with compound nylestriol tablet (CNT) and it s components Methods The studies consisted of acute and chro n ic toxicity test series including 5 isolated experiments in mice, rats and dogs LD 50 , acute toxicity in cardiovascular,respiratory and nervous systems, an d various organs of animals treated (1 week for acute tests and 6 months for chr onic tests ) with low and high doses of CNT were evaluated by observation of gen eral conditions, hematological,serum biochemical and systemic pathological exami nations Results (1) LD 50 of CNT was 66 6 mg/kg intrape ritonea lly and the maximal tolerance dose was 325 mg/kg intragastrically, (2) No acute toxicity in nervous,cardiovascular, and respiratory systems,and other organs cou ld be detected when 3-and 9-fold higher routine doses were given for one week ( 3) During 6 months of chronic toxicity study,36 7-and 144-fold routine doses of CNT showed no significant toxic effects on these animals,but a decrease in body weight, RBC and Hb was found and returned to normal 2 weeks after withdrawal of CNT, suggesting that it resulted from the decrease in food intake and malnutriti on Conclusion Except for loss of body weight and reversible a n emia which was in SD rats of chronic toxicity group, CNT in doses conresponding to routine dosage for postmenopausal osteoporosis and much higher than that show ed no notable toxicity in mice,SD rats and dogs

关 键 词：复方尼尔雌醇片 长期毒性 急性毒性 动物实验 CNT 毒性反应 

分 类 号：R595[医药卫生—内科学] R977.12[医药卫生—临床医学]