Zhuang Jia-ju, Wang Jing, Wang Zhi-ling, Gou Ling-yan
Instrumental Center of Bethune Military Medical College, Shijiazhuang 050081, China.
Wei Sheng Yan Jiu. 2005 Nov;34(6):716-9.
To elucidate the roles of Bcl-2 and Bax in experimental immunological liver injury in rat and the effect of lowering serum levels on the expression and the injury.
48 male Wistar rats were divided into six groups randomly. The animal model of iron low-load was created by intravenation of deferoxamine (DFO) or phlebotomy respectively, and immunological liver damage model was reproduced by injection of BCG (Bacilli Calmette Guein) and lipopolysaccharide (LPS). Then the following parameters were determined such as serum iron (SI) concentration, transferrin (TRF) concentration, total proteins (TP) volume, the serum activity of aspartate aminotransferase (AST), malondialdehyde (MDA) content, iron content (HIC), the expression of Bcl-2 and Bax proteins in liver tissue were assayed; the ratio of Bax to Bcl-2, apoptotic index (AI), and proliferative index (PI) were also calculated.
(1) The amount of Bax expression in liver injury group was significantly higher than that of control one, but no change in Bcl-2 expression. The ratio of Bax to Bcl-2 and AI augmented significantly, along with increased serum activities of AST and level of MDA, reduced volume of TP in liver injury animals. (2) The serum activity of AST and TP volume in both of the control groups with DFO and phlebotomy pretreatment remained at control level. Although the expression of Bax and Bcl-2, Bax/Bcl-2 ratio and AI were all higher than those of blank controls, the increased magnitudes of Bax/Bcl-2 ratio and Al were significantly lower than those of the liver injury animals. (3) The expression amounts of Bcl-2 and Bax increased in the injury animals induced after injecting DFO or phlebotomy, thus Bax/Bcl-2 ratio and Al increased. However, Bax/Bcl-2 ratio and AI of them were less than those of the injuries without lowered SI, and the magnitude of increased serum activity of AST was lower than that of the injuries, but no change in TP volume in the rats with lowered SI. The MDA levels in the injuries with lower value of serum iron were lower than those of the animals without lower SI.
The results show that the apoptotic process of hepatocyte accelerates in immunological liver injury, apoptosis may facilitate hepatocyte damage. Effect of iron on the expression of apoptosis regulating proteins have played an important role in apoptosis of immunological hepatic injury.
阐明Bcl-2和Bax在大鼠实验性免疫性肝损伤中的作用以及降低血清水平对其表达和损伤的影响。
48只雄性Wistar大鼠随机分为6组。分别通过静脉注射去铁胺（DFO）或放血建立低铁负荷动物模型，再注射卡介苗（BCG）和脂多糖（LPS）复制免疫性肝损伤模型。然后测定血清铁（SI）浓度、转铁蛋白（TRF）浓度、总蛋白（TP）含量、天冬氨酸转氨酶（AST）血清活性、丙二醛（MDA）含量、铁含量（HIC），检测肝组织中Bcl-2和Bax蛋白的表达；计算Bax与Bcl-2的比值、凋亡指数（AI）和增殖指数（PI）。
（1）肝损伤组Bax表达量显著高于对照组，而Bcl-2表达无变化。肝损伤动物中Bax与Bcl-2的比值和AI显著升高，同时AST血清活性增加、MDA水平升高、肝组织中TP含量降低。（2）DFO预处理对照组和放血预处理对照组的AST血清活性和TP含量均维持在对照水平。虽然Bax和Bcl-2的表达、Bax/Bcl-2比值和AI均高于空白对照组，但Bax/Bcl-2比值和AI的升高幅度显著低于肝损伤动物。（3）注射DFO或放血后诱导的损伤动物中Bcl-2和Bax的表达量增加，因此Bax/Bcl-2比值和AI升高。然而，它们的Bax/Bcl-2比值和AI低于未降低SI的损伤组，AST血清活性升高幅度低于损伤组，但降低SI的大鼠肝组织中TP含量无变化。血清铁值较低的损伤组MDA水平低于未降低SI的动物组。
结果表明免疫性肝损伤中肝细胞凋亡过程加速，凋亡可能促进肝细胞损伤。铁对凋亡调节蛋白表达的影响在免疫性肝损伤的凋亡中起重要作用。
