【摘要】 目的:探讨核因子-κB(NF-кB)及其下游因子肿瘤坏死因子-α(TNF-α)在绞窄性肠梗阻致急性肝损伤中的作用及机制。方法:将96只SD大鼠随机分为绞窄性肠梗阻模型组(模型组)和假手术组(对照组)。各组再随机分为4个亚组,每个亚组12只,分别于造模完成后6 h、12 h、24 h、48 h 4个时点处死,留取肝组织,采血1～2 mL。用免疫组织化学法测定各组肝内NF-кB活性及TNF-α蛋白含量,并测定血清ALT、AST水平。结果:模型组血清ALT、AST在造模完成后随时间逐渐升高,于24 h达高峰,与对照组相比,各时点均明显升高,差异有统计学意义(P<0.05)。模型组肝内NF-кB活性在造模完成后随时间逐渐升高,于12 h达高峰;同时TNF-α蛋白含量也随时间逐渐升高,于24 h达高峰。与对照组相比,除6 h组外,其余各时点均明显升高,差异有统计学意义(P<0.05)。结论:大鼠绞窄性肠梗阻发生后可致急性肝损伤,其损伤程度随时间逐渐加重;NF-κB在绞窄性肠梗阻的肝组织中被激活,并可增加TNF-α的转录表达,共同参与肝组织损伤的发生和发展。更多还原

【Abstract】 Objective:To investigate the roles and mechanisms of nuclear factor-kappa B(NF-κB)and its downstream factors — tumor necrosis factor-Alpha(TNF-α) in acute hepatic injury result from strangulated intestinal obstruction.Methods:The total of 96 male SD(Sprague-Dawley) rats were randomly and averagely divided into two groups:strangulated intestinal obstruction model group(model group) and sham-operated group(control group).The two groups further divided into four sub-groups,each has 12 rats.The rats in each sub-groups were killed on 6,12,24 and 48 h respectively after the models were completed,then liver tissues and 1～2 mL of blood were taken out.Hepatic NF-κB activity and TNF-α protein content was measured with immunohistochemical staining and image analysis in all groups.Levels of serum ALT and AST were determined at the same time.Result:Levels of secrum ALT,AST in model groups were gradually increased with time after the models were completed,and reached peak at 24 h;As compared with those in control groups,the levels of secrum ALT,AST were markedly increased in model groups at each time point(P<0.05).Levels of hepatic NF-κB activity in model groups were gradually increased with time after the models were completed,and reached peak in 12 h group;Meanwhile hepatic TNF-αcontent were markly increased and appeared peak in 24 h group;As compared with those in control groups,except the 6 h group,the NF-κB activity and TNF-α protein content were obviously increased in model groups at each time point(P<0.05).Conclusion:Strangulating intestinal obstruction of rats could induce acute liver injury,and the extent of its damage gradually increase with time.Hepatic NF-κB is activated after strangulation intestinal obstruction,and mediates the transcription and expression of TNF-α protein,which can collectively induce subsequent liver injure after strangulation intestinal obstruction.更多还原