【摘要】 目的探讨NF-κB诱骗寡脱氧核苷酸对大鼠内毒素性肝损伤的保护作用及其机制。方法60只SD大鼠随机分为对照组、内毒素(LPS)组、诱骗寡核苷酸(decoy ODNs)处理组。取各组大鼠肝组织检测NF-κB蛋白结合活性(EMSA),观察组织病理学改变(光镜)及肝细胞凋亡(TUNEL)。取静脉血检测AST(自动生化仪)以及TNF-α,IL-6的表达水平(ELISA)。结果与对照组相比,内毒素组NF-κB活性明显升高,诱发大量肝细胞凋亡,肝脏损伤明显;同时血清AST,TNF-α及IL-6明显升高(P<0.01)。与内毒素组相比,NF-κB诱骗寡核苷酸处理组NF-κB活性受抑制(P<0.01)、肝脏组织病理学改变和肝细胞凋亡明显减轻,血清中TNF-α和AST表达水平降低(P<0.01),但IL-6表达与内毒素组差异无统计学意义(P>0.05)。结论NF-κB诱骗策略能高效抑制NF-κB的活性,抑制其下游有害细胞因子的产生,从而减轻内毒素性肝损伤。更多还原

【Abstract】 Objective To study the protective effect of NF-κB decoy oligodeoxynucleotides(ODNs) on endotoxin-induced liver injury in the rat and its mechanism.Methods Sixty Sprague-Dawley rats were randomly divided into control group,endotoxin(LPS) group and NF-κB decoy ODNs group.Liver and serum samples were collected 24 h after operation.The NF-κB binding activity was detected with electrophoretic mobility shift assay(EMSA),histopathologic change of liver was examined by light microscope,and cell apoptosis was detected by TUNEL.Liver enzyme(AST),TNF-α and IL-6 in serum were also detected.Results Compared to control group,in LPS group,NF-κB was dramatically increased induced apoptosis of large numbers of hepatocytes,and severe liver damage,the expression of AST,TNF-α and IL-6 were also significantly increased(P<0.01).However,compared with control group in NF-κB decoy ODNs group,the activation of TNF-κB depressed,the hepatic histopathologic changes and apoptosis of hepatocytes were also relieved,and expression of TNF-α and AST levels decreased(P<0.01).On the other hand,the expression of IL-6 was not significantly decreased by NF-κB decoy compared with LPS group(P>0.05).Conclusions NF-κB decoy strategy can efficiently inhibit the binding activity of NF-κB,and thus suppress the production of downstream cytokines,which may play a crucial role in protecting the liver from endotoxin-induced injury.更多还原