NF-κB诱骗寡核苷酸对内毒素性肝损伤的保护作用和机制
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李敬东E-mail:lijingdong358@126.com

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国家自然科学基金资助项目(30300337;30700773)。


The protective effect of nuclear factor-κB decoy oligodeoxynucleotides on entotoxin-induced liver injury |and its mechanism
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    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。

    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.

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彭勇|李敬东|肖江卫|龚建平|刘作金|李寿柏. NF-κB诱骗寡核苷酸对内毒素性肝损伤的保护作用和机制[J].中国普通外科杂志,2010,19(1):48-52.
DOI:10.7659/j. issn.1005-6947.2010.01.011

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  • 收稿日期:2009-09-20
  • 最后修改日期:2009-12-18
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  • 在线发布日期: 2010-01-15