氯丙嗪、对乙酰氨基酚致大鼠肝损伤的实验研究  

Experimental Study on Liver Injury Rats Induced by Chlorpromazine and Paracetamol

作　　者：姚亚奔[1] 占俊[2] 于钟[2] 

机构地区：[1]厦门市第一医院,福建厦门361003 [2]中山大学附属二院消化内科

出　　处：《中国药师》2007年第11期1085-1087,共3页China Pharmacist

摘　　要：目的:探讨药物引起大鼠急性肝细胞型肝损伤和急性肝内淤胆型肝损伤的特点。方法:将60只SD大鼠随机分为3组,对照组,对乙酰氨基酚组和氯丙嗪组。用氟丙嗪、对乙酰氨基酚分别建立急性肝内淤胆型肝损伤和急性肝细胞型肝损伤大鼠模型,计算各组R值(R=ALT超过正常值的倍数/ALP超过正常值的倍数),检测各组大鼠的肝脏生化,观察各组大鼠的肝脏病理。结果:对乙酰氨基酚组:R_(对乙酰氨基酚组)=6.48±2.37(n=20),AST、ALT高于对照组5.34倍(P<0.05);肝脏病理改变为肝小叶中央实质细胞点状及灶性坏死。氯丙嗪组:R_(氯丙嗪组)=1.12±1.05(n=17),ALP、TBA高于对照组2.56倍(P<0.05);肝脏病理改变为肝实质细胞坏死不明显,但电镜下毛细胆管改变可见。结论:急性肝细胞型肝损伤以肝实质细胞的坏死表现为主;急性肝内淤胆型肝损伤以胆管系统损害和胆汁淤积为主,肝实质细胞坏死表现不明显。Objective： Detect liver biochemistry and liver pathology of the two kinds clinical drug-induced liver injury. Method： SD rats were divided into 3 groups： controlled group, paracetamol group and Chlorpromazine group, paracetamol was used to establish animal model of acute hepatic cell type, and Chlorpromazine was used to establish animal model of acute cholestasis type. Then, liver biochemical indicator was detected, R value was calculated（ R =The multiple of ALT overtopping normal value/The multiple of ALP overtopping normal value） , liver pathology was observed. Result： R paracetamol group =6.48 ± 2.37 （n =20）, ALT and AST were five times higher in the Paracetamol group rats than those in the controlled group （P 〈 0.05 ） , In the Paracetamol group rats , liver pathology was found punctiform necrosis or focal necrosis; R chlorpromazine group = 1.12 ± 1.05（ n = 17） , ALP and TBA were two times higher in chlorpromazine group rats than those in the controlled group（ P 〈 0.05 ） , In chlorpromazine group rats, occasionally punctiform necrosis was found, but cholangiole expansion, microvilli reduction and deformation were found with electron microscope. Conclusion： The major characteristic of acute hepatic cell type drug-induced liver injury is hepatic parenchymal cells necrosis and apoptosis. The major characteristic of acute cholestasis type drug-induced liver injury is bile vessel system damage and cholestasis, but hepatic parenchymal cells necrosis are not obvious.

关 键 词：药物性肝病 肝损伤 动物模型 对乙酰氨基酚 氯丙嗪 

分 类 号：R965.1[医药卫生—药理学]