乙烷硒啉对大鼠连续灌胃给药十二周的长期毒性试验研究  

A Study of Long-term(12 Weeks) Toxicity Test on Rats with Ethaselen

作　　者：林飞[1] 周立娜[2] 梁怿[1] 吕廉[1] 

机构地区：[1]中国药品生物制品检定所,北京100050 [2]中国医科大学,辽宁沈阳110001

出　　处：《肿瘤基础与临床》2008年第5期369-373,共5页journal of basic and clinical oncology

基　　金：国家自然科学基金项目(编号:30472036)

摘　　要：目的研究乙烷硒啉连续给药后对大鼠的毒副反应及其严重程度。方法采用SD种大鼠,受试物共分成3个给药组(1 000mg/kg、400 mg/kg和160 mg/kg)和1个溶剂对照组,连续口服给药12周,停药后再观察4周,进行一般症状观察,血象、生化、脏器解剖、脏器系数和组织病理学等检查。结果给药12周高剂量组的大鼠体重增长缓慢,摄食量减少,谷草转氨酶、碱性磷酸酶、总胆红素、总胆固醇增高,葡萄糖降低,心脏、肝脏、脾脏、肾脏和睾丸脏器系数值升高,肝脏存在肝细胞脂肪性变,个别已经发展到轻度肝硬变。停药4周大鼠的体重增长差值有明显的缩小,总胆固醇增高,心脏、肝脏脏器系数值仍有一定升高,肝脏轻、中度肝细胞脂肪性变和早期肝硬变仍然存在。结论乙烷硒啉在相当于临床人拟用量70倍时,出现体重增长明显缓慢、血液葡萄糖降低、肝功能和脂代谢等异常、肝脏等脏器系数值增加、肝细胞脂肪性变和早期肝硬变等的毒副反应。大鼠用药的无明显毒副反应剂量为160mg/kg。Objective To observe the toxic reactions and degrees in rats disposed with ethaselen, continually. Methods The test was divided into three groups （ 1 000 mg/kg, 4 00 mg/kg, 160 mg/kg） and a solvent control group. SD rats were professed to be convinced continually orally for 12 weeks. We observed again for 4 weeks after stopping the medicine, and carried on a general symptomatic an observation, hemateikon, bio-chemistry, viscera dissection, viscera coefficient and histopathology, etc. Results Expectant medicine high dose group of rats, the rats appeared the lentitude of avoirdupois increase, and appetite quantity decreased, the serum AST, ALP, BIL and Cho Went up obviously, the glucose lowered, the coefficient value of heart, liver, spleen, kidneys, and testicle certainly went up, the liver cell fattiness changed or rigidity change of not importance. Expectant medicine the obvious reduction of toxicity reactions of rats .could be seen. Conclusion After using ethaselen, the toxicity reactions of the avoirdupois increase lentitude can be found, the serum glucose can lower, liver function, fat metabolism and liver coefficient value can go up obviously, the liver cell fattiness change or rigidity change is not important, with the dosage of 70 times for the clinical persons. The rats in the 160 mg/kg have no obvious medicine toxicity reaction.

关 键 词：乙烷硒啉 SD大鼠 长期毒性 肝功能 脂代谢 

分 类 号：R730.59[医药卫生—肿瘤]