高脂饮食兔肝在不同剂量辛伐他汀作用下的病理表现  

Pathological manifestation of liver cells of rabbits with cholesterol diet treated with different doses of simvastatin

作　　者：于洁[1] 高传玉[2] 任颖[3] 

机构地区：[1]郑州大学第一附属医院老年病科内科部,450052 [2]郑州大学人民医院心血管科 [3]郑州大学人民医院临床病理科

出　　处：《中国实用医刊》2012年第13期51-54,共4页Chinese Journal of Practical Medicine

摘　　要：目的复制动脉粥样硬化兔模型，比较不同剂量辛伐他汀作用下兔肝的病理表现，以了解高剂量他汀对肝脏的不良反应。方法实验于2008年2月至2008年7月在郑州大学人民医院心血管内科及病理科实验室完成。选择雄性4个月龄新西兰大白兔20只，分笼饲养。5只饲喂正常的全价颗粒饲料，自由饮水，观察1周后进入实验。高脂饮食组15只饲以含1．5％胆固醇的高脂饮食，其中高脂饮食组又分为对照组5只和实验组10只。3个月后实验组即开始服用辛伐他汀（5只5mg／d、5只10mg／d），30d后行兔安乐死，取兔肝做病理切片。结果纳入动物20只，均进入结果分析。高脂饮食（90d）和正常饮食相比，出现了肝细胞浊肿及个别慢性炎细胞浸润。高脂饮食加辛伐他汀5mg／d组和单纯高脂饮食组相比，肝细胞弥漫性水样变性；高脂饮食加辛伐他汀10mg／d组则除了上述改变还出现了肝细胞坏死等急性中毒性改变。结论大剂量他汀类药物的，临床应用，其肝脏的毒性作用仍应给予重视。要尽量做到他汀强效与安全的辨证统一。[ Abstract] Objective To establish models of atherosclerosis of rabbits and compare the patho- logical changes of liver cells administered with different doses of simvastatin and cholesterol diet, to dem- onstrate adverse effect in high dose of simvastatin. Methods The experiment was carried out in the la- boratory of department of cardiovascular medicine, people＇ s hospital of Zhengzhou University from Febru- ary to July 2008. Twenty male New Zealand rabbits aged 4 months were fed with a standard diet in sepa- rate cages for 1 week without inhibiting drinking. One week later, the rabbits were fed on normal diet （normal group, n = 5） ,or a cholesterol diet （1.5%） （n = 15： contrlo group, n = 5; treating group, n = 10,respectively）. There were 5 rabbits fed simvastatin of 5 mg/d and the other 5 rabbits were fedlOmg/d of it in the months. These rabbits treating group after 3 were also administered with aspirin. Rabbits were killed 120 days after a cholesterol diet（ 1.5% ） and liver tissues were harvested. They were fixed with 4% neutral buffered for- malin, embeded in paraffin and stained with hematoxylin and eosin. Slices were observed with light mi- croscope to judge the pathological changes of liver ceils administered with simvastatin and cholesterol di- et. Results All the 20 rabbits entered the result analysis. The liver cells were extensivelly hydropic de- generation in the rabbits treated with simvastatin （5 mg/d）. The extensive hydropic degeneration was modest and reversible. The simvastatin （5 rag/d） was well tolerated by most rabbits. The liver cells were partly necrosis and the whole photo demonstrated acute toxicity in the rabbits treated with simvastatin（ 10 mg/d）. Conclusions We should pay more attention to the adverse effect to liver cells administered with the high dose of simvastatin. The most effect of statins should be consistent with security.

关 键 词：膳食 动脉粥样硬化 动物模型 辛伐他汀 肝脏 不良反应 

分 类 号：R-332[医药卫生]