洛伐他汀在巴马香猪体内的长期毒性试验

Long-Term Toxicity Test of Lovastatin in Bama Miniature Pig

为研究洛伐他汀在巴马香猪体内为期42d的长期毒性特点，以抗动脉粥样硬化药物洛伐他汀为模型药，选择健康6月龄雄性巴马香猪为实验对象，经灌胃途径给药（12mg·kg^-1和135nag·kg^-1），观察给药后的临床表现、血液学、血生化、脏器系数和组织病理学等指标进行药物毒性的评价。结果主要毒性反应在135mg·kg^-1组，给药后巴马香猪出现了竖毛、腹泻等症状，总采食量和体重减轻；血液血检查显示白细胞总数有所增加，红细胞总数、血红蛋白含量和血小板计数明显下降；血液生化检查显示ALT、AST、ALP和cK升高2—10倍，肌酐和尿素有所升高。同时，组织病理学分析结果显示，巴马香猪出现了与人相似的肝肾病理改变。可见洛伐他汀给药后，巴马香猪在高剂量组可大部分呈现洛伐他汀在人临床出现的毒理反应，表明巴马香猪能敏感的反映洛伐他汀的潜在毒性。

To study the long - term toxicity of lovastatin in Bama minipigs, 6 - month male Bama minipigs were randomly divided into two dose groups（ 12 mg·kg^-1 and 135 mg·kg^-1 ） and a blank group. The drug was given once a day for 42 successive days. Manifestation and behaviors, hematology, blood chemistry and histopa- thology were detected. The results revealed that 135 mg·kg^-1 had serious toxicity. The main toxic manifestations were piloerection and diarrhea, body weight loss and declined foraging quantity. Compared to control, total white cell count increased, however red blood count and hemoglobin and blood platelets count declined. ALT,AST,ALP and CK were increased 2 - 10 fold. The pathological histology analysis result showed that there were some morphological abnormalities and characteristic pathological change in the major target organ, liver and kidney. It could be concluded that Bama miniature pigs could sensitively show＇toxic reactions that observed in clinical therapy of lovastatin.