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重组巴曲酶对大鼠长期毒性观察

Long-term Toxic Effect of Recombinant Batroxobin on Rats
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摘要 目的研究重组巴曲酶(rBAT)连续静脉注射30d对大鼠的长期毒性。方法健康SD大鼠按体重随机分为低、中、高剂量组(3.0、10.0、30.0KU·kg-1)和溶媒对照组(n=20)。连续30d尾静脉注射给药。末次给药后处死一半动物做病理解剖,另一半停药后继续观察15d。观察症状和检测指标包括:一般症状;血液学指标;血液生化指标;凝血指标;非特异性免疫学检查;抗体检测;病理检查等。结果rBAT可能对大鼠的CT有一定的影响,且不同剂量对CT的作用不同;rBAT能显著降低大鼠血浆Fig含量,且呈剂量依赖性。30d雄性大鼠血清ALT呈剂量依赖性的升高。以上作用均是可逆的。结论rBAT对大鼠凝血系统及肝功能有一定的可逆的毒性作用。大鼠静脉注射rBAT的安全剂量为3KU·kg-1。 Aim To study the long-term ( iv for 30 days) toxic effect of recombinant batroxobin (rBAT) on rats. Methods Eighty rats (40 male and 40 female) were randomly divided into 4 groups according to their body weights ( n = 20) : rBAT treatment groups ( 3.0,10.0, 30. OKU ·kg^-1 of rBAT once daily for 30 consecutive days through iv injection) and acetate buffer treatment group ( as control). Haft of the animals in each group were sacrificed at the end of medication and the rest were sacrificed after another 15 days' recovery. The general symptoms, the hematological and biochemical parameters, blood coagulation parameters, pathologic changes and the antibody detection were observed or performed in each group. Results Different doses of rBAT had different effects on CT in rats and rBAT could dose-dependently decrease Figrinogen in rats significantly. At d30, rBAT caused a dose-dependent increase in ALT in the treatment groups. All these effects were reversible. Conclusion rBAT has pharmacological and toxicological effects on the hematology system and liver in rats, and the effects of rBAT are reversible. The safe dose of rBAT for rats is 3.0KU·kg^-1.
出处 《解放军药学学报》 CAS 2008年第6期492-495,共4页 Pharmaceutical Journal of Chinese People's Liberation Army
关键词 重组巴曲酶 长期毒性 大鼠 Recombinant batroxobin Long-term toxicity Rat
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