改变铁负荷对免疫性肝损伤大鼠肝细胞脂质过氧化与凋亡的影响

目的　研究改变铁负荷后 ,免疫性肝损伤大鼠肝细胞脂质过氧化与细胞凋亡的变化 ,探讨免疫性肝损伤的作用机制。方法　将 32只Wistar大鼠随机分成 4组 ,采用放血法复制低铁模型 ,采用卡介苗加脂多糖诱导法复制免疫性肝损伤模型。观察各处理组血清总蛋白 (TP)含量及天门冬氨酸氨基转移酶 (AST)活性的变化 ,观察肝组织中丙二醛 (MDA)含量、超氧化物歧化酶 (SOD)活性及细胞凋亡相关指标的变化。结果　通过相应损伤对照组比较 ,低铁肝损伤组AST活性增高幅度和TP含量的降低幅度均小于肝损伤组 ,各损伤组MDA含量均增高 ,SOD活性均降低。与正常对照组比较 ,低铁对照组MDA显著降低、Bcl 2和Bax表达量、Bax Bcl 2比值及凋亡指数 (AI)值均增高 ,肝损伤组Bcl 2表达量基本不变。低铁肝损伤组Bcl 2表达量显著高于肝损伤组。与相应损伤对照组比较 ,各损伤组Bax表达量显著升高 ,肝损伤组Bax Bcl 2比值和AI值明显增高 ,低铁损伤组Bax Bcl 2比值和AI值均下降 ,低铁损伤组增殖指数 (PI)值增高幅度大于单纯肝损伤组。结论　降低铁负荷 ,减轻了肝损伤的程度 ,其作用机制可能是通过改变肝细胞脂质过氧化 ,影响Bcl 2和Bax基因表达的平衡和细胞凋亡和细胞增殖之间的平衡所致

The Effets of Iron Load on the Changes of Lipid Peroxidation and Apoptosis in Hepatocyte of Experimental Immunological Liver Injury in Rat

Objective To investigate the changes of lipid peroxdation and apoptosis in hepatocyes of experimental immunological liver injury in rat so as toelucidate the mechanism of immunological liver injury,while reducing iron load Methods 32 male Wistar rats were divided into four groups at random Iron low load groups'models were made by phledotomy Immunological liver damage models were established by injection of micro lipopolysaccharide (LPS) into rats primed by BCG (Bacilli Calmette Guerin) Then the following parameters were examined such as total proteins (TP)and aspartate aminotransferase (AST) in seum Malondialdehyde (MDA),superoxide dismutase (SOD),and the index relative to apoptosis in liver tissue extracs were estimated Results In comparison with each control group,the activities of AST were lower and the levels of TP were higher in phlebotomy injury group group than those in pure injury one,and the levels of MDA augmented and the activities of SOD reduced in two injury group. Compared to control group,the levels of MDA in phlebotomy control group declined significantly,and the amounts of Bcl 2,and Bax gene expression,the ratio of Bax to Bcl 2 and the Vulues of apoptosis index (AI)in phlebotomy contol group Chung The amount of Bcl 2 gene expression in pure injury group didn' t change The amount of Bcl 2 gene expression in phlebotomy injury grup was higher than that of pure injury group Compared with each control group,the amounts of Bax gene expression in phlebotomy injury group and pure injury group increased signifi cantly.The ratio of Bax to Bcl 2,and the values of AI in pure injuy group inceased significantly but decrased in phlebotomy injury group The values of proliferation indexex (PI) in phlebotomy injury grup were higher than that of pure injury group Conclusion Reducing iron load can improve the degree of immunological liver damage by changing the reaction of lipid peroxidation which influences the balance of expression between Bcl 2 and Bax gene and the balance between apoptosis and proliferation of hepatocytes