三氧化二砷对逆行隔离灌注大鼠肝脏毒性的观察  

As2O3 toxicity on rat liver during retrograde isolated hepatic perfusion

作　　者：叶华[1] 陆才德[2] 郑四鸣[1] 黄静[2] 何向蕾[3] 吴胜东[2] 

机构地区：[1]宁波大学医学院,315211 [2]宁波大学医学院附属李惠利医院肝胆胰外科 [3]宁波大学医学院附属李惠利医院病理科

出　　处：《中华普通外科杂志》2009年第6期500-503,共4页Chinese Journal of General Surgery

基　　金：国家自然科学基金资助项目（30872972）

摘　　要：目的观察不同剂量三氧化二砷（As2O3）在大鼠逆行隔离灌注（RIHP）模型中对肝脏毒性作用。方法104只体重300～400g雄性SD大鼠中8只为术前正常对照组，其余大鼠分A、B、C、D4组，每组24只。A组灌注不含As2O3的乳酸林格氏液，B、C、D组灌注As2O3的剂量分别为0．75mg／kg、1．5mg／kg、3mg／kg。实验组均采用RIHP，即经肝动脉灌注As2O3溶液，经肝静脉逆行灌注乳酸林格氏液，门静脉为流出道；灌注时间为15min，速度1mL／min。对照观察实验组术后1、2、3、7d各时点肝酶学变化、肝组织学改变和术后生存情况；检测C组大鼠术中和术后第1天的肝循环和体循环中As2O3浓度。结果实验组ALT、AST峰值均出现在术后第1天，至术后3～7d恢复正常。A和B组ALT、AST峰值问差异无统计学意义，A和C，A和D，B和C，B和D、C和D各组问ALT、AST峰值差异均有统计学意义（FALT=40．811，FAST=48．212，均P〈0．01）。D组术后第7天时仍与术前正常对照组及A、B、C各组间差异均有统计学意义（FALT：13．928，FAST=17．942，均P〈0．01），且术后肝组织出现片状坏死等较严重的损害。肝循环和体循环As2O3血药浓度峰值分别为（13．21±0．82）μg／ml和（0．09±0．008）μg／ml，二者比较差异有统计学意义（t=35．758，P〈0．01）。结论在大鼠RIHP模型中，当As2O3灌注剂量不超过1．5mg／kg时肝脏遭受的损害是可逆的。Objective To study As2O3 toxicity on rat liver in a retrograde isolated hepatic peffusion model. Methods In this study 104 male Sprague-Dawley rats weighing between 300 and 400 g were used. Eight male SD rats were used for preoperatively normal control and the remaining rats were randomly divided into 4 subgroups receiving As2O3 at dosage of 0 mg/kg, 0. 75 mg/kg, 1.5 mg/kg, 3 mg/kg respectively. Modified RIHP was used in which As2O3 was infused through hepatic artery. Ringer＇s lactate was retrogradly infused through hepatic veins and the portal vein was used as the outflow tract. Hepatic function, pathology and liver enzymes were assessed at different time points. As2O3 concentration was monitered during the perfusion in rats of subgroup C. Results Serum ALT and AST rose to the peak on the first day, returning to normal after 3 or 7 days in all four subgroups. There was no difference between the peak levels of serum ALT and AST between subgroup A and B. Differences in serum ALT,AST level between subgroup A and C, A and D, B and C, B and D, C and D were all statistically significant （FALT =40. 811 ,P 〈0. 01 ; FAST = 48. 212,P 〈0. 01 ）. On day 7, ALT and AST in subgroup D were still statistically higher when compared with that of other subgroups and normal contro]（FALT = 13. 928,P 〈0. 01 ; FAST = 17. 942,P 〈0. 01 ）, and the hepatic pathology showed necrosis of the hepatocyte. The peak levels of As2O3 were 13.21 ± 0. 82 （μg/ ml） and 0.09 ± 0. 008 （ μg/ml ） in rats liver and systemic circulation in subgroup C during isolated perfuision. There were significant differences between the peak levels of concentration of As2O3 in rats liver and systemic circulation （ t = 35. 758 ,P 〈 0. 01 ）. Conclusions The hepatic toxicity is reversible caused by As2O3 when given at a dosage of 1.5 mg/kg of As2O3 in a murine model of RIHP.

关 键 词：肝 药物毒性 三氧化二砷 大鼠 

分 类 号：R686[医药卫生—骨科学]