早期生长反应基因-1与急性胰腺炎大鼠肝损害的关系

摘要

目的 通过观察早期生长反应基因-1在大鼠不同程度AP及AP发病后不同时间肝组织的表达,及检测血清炎性细胞因子与肝实质酶水平,研究早期生长反应基因-1与AP肝脏损害的关系.方法 先将24只雄性Wistar大鼠随机均分为4组,即A、B、C、D组,分别于胆总管内逆行注入生理盐水或不同浓度牛磺胆酸钠溶液,3h后处死动物,留取血清、肝脏组织.另将30只雄性Wistar大鼠随机均分为5组,即E、F、G、H、I组,5%牛磺胆酸钠溶液胆管内逆行注射后1h、3h、6h、12h、24h处死动物同上留取标本.检测血清AST、LDH、TNF-a、IL-113水平,并对肝组织进行EGR-1免疫组化染色.结果 (1)A、B、C、D四组动物炎性细胞因子TNF-a、IL-1β,肝实质酶AST及LDH水平均随着牛磺胆酸钠浓度的升高而逐渐上升;(2)肝组织进行EGR-1免疫组化染色显示,在不同程度AP组,EGR-1表达量随AP病情程度加重而逐渐增加,并与反映AP病情指标如肝实质酶、炎性细胞因子水平均呈显著正相关,且表达部位也有所不同.EGR-1在AP发病后不同时间肝组织的表达,具有极明显的细胞种类与部位的差异.结论 EGR-1可能与AP时伴发的肝脏损害有关,其机制可能与其介导炎性细胞因子生成有关.%Objective To investigate the possible role of early growth response factor-1(EGR1)in liver injury in rats after acute pancreatitis(AP).Methods Twenty-four male Wistar rats were randomized into 4 groups.Normal saline was injected through the common bile duct(CBD)into the rats in group A and taurocholate sodium solution with different concentrations was injected through the CBD into those in group B,C and D.All the animals were sacrificed 3h after the injection and theblood and liver samples were harvested.Another 30 male Wistar rats were randomized into 5 groups.The rats in these 5 groups were sacrificed at 1,3,6,12 and 24 h after the injeetion,respectively.The serum levels of AST,LDH,TNF-αand IL-1β were measured in all the 9 groups.EGR-1 in liver paraffin sections was semi-quantitatively determined after immunohistochemical staining.Resnlts 1)With stepwise rising concentration of taurocholate sodium,the levels of AST,LDH,TNF-α and IL-1β were getting higher and EGR-1 staining was getting more intense.2)Positive staining of EGR-1 in the liver was more intense in severe acute pancreatitis models.Furthermore,EGR-1 staining sites were different among AP models with different degrees of severity.Another interesting finding was that the positive staining cells and intracellular sites of EGR-1 displayed notable difference in livers harvested at different time phases after pancreatitis induction.Maximal EGR-1 staining emerged 3h after pancreatitis induction during our observing period.Conclusion EGR-1 may play an important role in liver injury during AP,and the possible mechanism might be related to its mediated production of inflammatory cytokines such as TNF-α.