铁过度负荷对大鼠免疫性肝损伤的影响及血管紧张素的作用  

Effect of iron overload on experimental immunological liver injury in rats and the role of angiotensin

作　　者：庄甲举[1] 张亚超[1] 张维立 姜红[1] 刘会敏[1] 王憬[1] 

机构地区：[1]白求恩军医学院生理教研室 [2]66481部队医院

出　　处：《卫生研究》2010年第1期101-104,共4页Journal of Hygiene Research

摘　　要：目的探讨铁过负荷和血管紧张素Ⅱ一型受体(AT1)阻断剂Losartan(LOS)在大鼠免疫性肝损伤中的作用。方法雌性大鼠50只分为5组(对照,肝损伤,肝损伤+LOS,肝损伤+右旋糖酐铁(ID)和肝损伤+ID+LOS)。采用卡介苗(BCG)加脂多糖(LPS)诱导法复制免疫性肝损伤模型;通过腹腔注入ID建立铁过负荷动物模型。检测血清铁(SI)、转铁蛋白(TRF)、总蛋白(TP)含量及天门冬氨酸氨基转移酶(AST)活性;检测肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和铁(HIC)含量;采用流式细胞计量分析检测细胞凋亡调节蛋白基因bcl-2和bax表达量的变化,计算细胞凋亡指数(AI)、细胞增殖指数(PI)和bax与bcl-2比值(bax/bcl-2)。结果(1)肝损伤大鼠AST活性高于对照组、TP和TRF含量低于对照组,MDA含量增加伴有SOD活性降低;bax表达量、bax/bcl-2和AI均大于对照组。(2)与肝损伤动物比,肝损伤+ID大鼠AST活性升高,MDA升高,bax表达量、bax/bcl-2和AI均增大;HIC高于对照组。(3)与肝损伤大鼠比,肝损伤+LOS组的AST活性降低,TRF升高;MDA含量降低,SOD活性升高;bcl-2表达量增加,bax/bcl-2和AI减小。(4)肝损伤+ID+LOS组的AST活性和MDA含量小于肝损伤+ID组,而TRF高于肝损伤组。结论铁过负荷增加脂质过氧化并易化细胞凋亡,加重免疫性肝损伤。血管紧张素Ⅱ易化这一肝细胞损伤过程。Objective To investigate the effect of iron overload on experimental immunological liver injury in rats and the roles of losartan （LOS）,which is the selective antagonist of angiotensin Ⅱ receptor subtype AT1.Methods Fifty male Wistar rats were divided by random into five groups （control,liver injury,liver injury＋LOS,liver injury＋ID and liver injury＋ID＋LOS）.Immunological liver injury model was reproduced by intravenous injection of BCG （Bacilli Calmette Guein） and then lipopolysaccharide （LPS）.Iron overload model was created by intraperitoneal injection of iron dextran （ID）.Serum iron （SI）,transferrin （TRF）,total protein （TP）,the activity of asparatate aminotransferase （AST） and malondialdehyde （MDA） and liver iron （HIC） were tested.The expression of bcl-2 and Bax and the bax/bcl-2 ratio in hepatocyte were tested by flow cytometric analysis.Apoptotic index （AI） and proliferative index were also calculated.Results （1） In comparison with blank control group,the activity of serum AST was higher.Serum TP and TRF were lower in liver injury animals.Liver MDA increased significantly and along with a lower SOD activity.The expression of Bax in liver injury group was significantly higher than that in control group.The bax/bcl-2 ratio and AI increased significantly in liver injury group.（2） Compared with liver injury group,the animals treated with ID showed an increase of serum AST activity,increased MDA and the expression of bax,the bax/bcl-2 ratio and AI.HIC was higher than the control group.（3） Compared with liver injury group,the activity of serum AST was lower and TRF was higher,MDA was reduced and SOD activity increased in animals treated with LOS.The expression of bcl-2 was increased,bax/bcl-2 ratio and AI decreased in this group.（4） In comparison with ID treated liver injury animals,the activity of AST and the content of MDA,and TRF increased in the animals treated with ID plus LOS.Conclusion The immunological liver injury could be aggravated

关 键 词：肝损伤 铁 免疫性 血管紧张素 

分 类 号：Q593.1[生物学—生物化学] Q58