摘要
实验选择ＳＤ大鼠，分为４组，观察不同剂量的环孢素Ａ（ＣｙｃｌｏｓｐｏｒｉｎｅＡ，ＣｓＡ）喂大鼠出现的一般表现、组织学及超微结构变化。大鼠用药后７ｄ内出现明显的肝细胞损害，表现为血清谷丙转氨酶（ｓＧＰＴ）、碱性磷酸酶升高，总蛋白及白蛋白降低。这种变化以双倍剂量组最明显，ｓＧＰＴ可高达１７６６．３０ｎｍｏｌ·ｓ－１·Ｌ－１，第４２天后稍有缓解。组织学及超微结构的改变提供了肝毒性变化的组织学依据。结果表明：ＣｓＡ所致的肝毒性具有明显的时相效应。靶器官的损害程度与剂量、服药时间及血药浓度密切相关。本实验为预防ＣｓＡ的肝毒性、指导临床合理使用ＣｓＡ、有效地提高移植物及患者的存活率提供了依据。
The animal model of hepatotoxicity reaction was produced in SD rats which were devided into 4 groups:double dose group with CsA 30 mg/(kg.d),single dose group with CsA 15mg/(kg.d),liverprotected group with CsA 15mg +silymarin 25 mg/(kg.d),and control group.The results showed that the level of serum glutamine pyruvic transaminase (sGPT) and akaline phosphatase (AKP) increased,and that of total protein and albumin decreased in the rats of each experimental group in the first 7 days of administration.These changed most markedly in double dose group,with sGPT up to 1766. 30 nmol·s-1·L-1.and began to fade at the 42 nd day.These results suggest that CsA-induced hepatotoxicity has a noticeable time -phase effect.The histologic and ultrastructural changes agree with that observed in drug intoxication by and large,though the former appeared more severe.There is an evident correlation between drug dosage and time of administrations and CsA toxicity.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
1995年第6期544-549,共6页
Academic Journal of Second Military Medical University
关键词
环孢素
肝毒性
毒理学
cyclosporine A
hepatotoxicity
blood drug concentration
histology
ultrastructure
rats
