决奈达隆和胺碘酮对大鼠肝脏功能及组织的影响

目的 研究决奈达隆、胺碘酮对大鼠肝脏功能和组织的影响。方法 随机选择雄性SD大鼠30只,分为对照（NC）组,决奈达隆（DR50）组,胺碘酮（AM50）组,每组10只。每天专业灌胃器给药1次,DR50组和AM50组给药剂量均为50 mg·kg-1·d-1,对照组给予等容积生理盐水,给药14周。给药期间观察SD大鼠一般状况,每周测体重,于2周,10周,14周末抽取静脉血检测谷丙转氨酶（ALT）,谷草转氨酶（AST）,碱性磷酸酶（AKP）,总蛋白（TP）,甘油三酯（TG）的变化。 14周末处死称取肝脏重量,计算脏器系数,并行肝脏病理组织检查。结果 三组体重增长速度相当,AM50组肝脏重量及脏器系数大于其他两组。实验过程中AM50组和DR50组ALT,AST均小于NC组,10周可见NC组AKP水平小于其他两组;AM50组TP水平于14周轻度大于其他两组;DR50组TG水平2周高于其他两组,10周TG水平较前升高,大于其他两组;14周可见三组TG水平较前明显降低,以DR50组为著。病理检查可见AM50组肝脏部分空泡样变性,DR50组脂肪样变性,电镜检查可见线粒体损伤。结论 胺碘酮和决奈达隆未引起体重下降和明显肝功能变化,但可导致肝细胞的线粒体微小变化。胺碘酮可造成肝脏重量增加,胆汁分泌障碍,决奈达隆可引起脂质淤积。

The effect of dronedarone and amiodarone on hepatic function and morphology in rats

Objective To investigate the effects of dronedarone and amiodarone on hepatic function and morphology in rats. Methods Thirty male SD rats were randomly divided into 3 groups, with 10 in each group：normal control （NC） group,dronedarone（DRS0） group（ig 50 mg · kg^-1· d^-1 ） and amiodarone（AM50） group（ig 50 mg · kg^-1· d^-1 ） ,the NC group was given saline with the same volume, and other two groups were fed drugs for 14 weeks respectively. During treat- ment observed the growth of weight, alanine aminotransferase （ ALT）, aminotransferase （ AST ）, alkaline, phosphatase （AKP）, triglyceride （TG）, total protein （TP）, which were measured in the 2nd , 10th, 14th week. All of the rats were killed , hepatic weight, hepatic weight/body weight coefficient, hepatic , optical microscope pathologic and electron microscope ex- amination of hepatic were performed. Results The growth of weight was similarity in three groups,the hepatic weight was higher in AMS0 group, so as to the hepatic weight/body weight coefficient. Meanwhile the ALT, AST levels were less than the NC group. The AKP level in the NC group was less than AM50 and DRS0 group,the level increased in the NC group and AM50 group,but decreased in DR50 group, The TP level was higher in AM50 group than that in the other groups in 14th week, The TG level was higher in DRS0 group than the NC groups in the second week. In the tenth week , but the TG level trended downward over time, which was more notable in DR50 group. Hepatic histopathologic examination configure thatparts of liver cell vacuolar degeneration in AM50 group and adipose degeneration in DR50 group electron micros- copy showed the damage of hepatic cell mitochondria. Conclusion Amiodarone and dronedarone fails to cause the notable changes of weight and hepatic function, but lead to the damage of hepatic cell mitochondria. Amiod- aorne can increase the hepatic weight,lead to dysfunctionof bile secretion. Dronedarone can cause lipid deposition.