摘要
目的 探讨核因子 κB(NF κB)靶向性寡核苷酸 (ODN )“圈套”策略对创伤性炎症大鼠肝脏损伤的作用。方法 Wistar大鼠 96只 ,随机分成对照组、创伤性炎症组、“圈套”ODN组和变异“圈套”ODN组 ,各组动物分别于术后 3、6、12、2 4、48和 72h分批处死。运用凝胶迁移变动分析 (EMSA)检测创伤性炎症术后肝脏组织NF κB的活性及合成“圈套”ODN的体外竞争抑制试验。检测血清转氨酶水平 ,在光镜下观察肝细胞损伤程度 ,电镜下观察肝脏超微结构改变 ,以线粒体的肿胀程度作为肝细胞损伤的评价指标。结果 创伤性炎症后 3h肝脏NF κB的活性开始升高 ,12h达高峰 ,72h后基本恢复正常。“圈套”ODN在体外能有效地抑制NF κB活性。血清ALT含量在伤后明显上升 ,于 2 4h达高峰 ,肝细胞出现明显的水肿、变性和坏死 ,肝小叶结构破坏明显。“圈套”ODN治疗 6h后 ,大鼠血清ALT水平明显降低 ,肝小叶结构损伤明显好转 ,线粒体的肿胀明显减轻。结论 NF κB靶向性“圈套”ODN通过特异性抑制NF κB活性 。
Objective To study the effects of decoy strategy targeted to nuclear factor kappa B (NF κB) on rats liver damage after traumatic inflammation.Methods 96 Wistar rats were randomized divided into 4 groups:control group,traumatic inflammation group,decoy ODN group and mutant decoy ODN group.These animals were killed on the 3,6,12,24,48 and 72 h respectively to determine the contents of plasma ALT.Hepatocytes were isolated and nuclear protein was extracted,then DNA binding activity of NF κB was measured by EMSA.Decoy ODN's competition inhibition effects were assayed by EMSA.The degree of hepatocytic necrosis was observed by a light microscope and the ultrastructural changes of liver by an electron microscope.Results After traumatic inflammation,DNA binding activity of NF κB in liver was increased markedly.Decoy ODN could effectively inhibit the activity of NF κB ex evo.Plasma ALT levels were markedly increased.The serious hepatocytes degeneration,swelling and necrosis were observed.After using Decoy ODN,plasma ALT levels were significantly decreased.All these pathological changes noted above were alleviated partially.Conclusion Decoy strategy targeted to NF κB could effectively inhibit rats' liver damages through inhibiting specifically the activity of NF κB.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2003年第10期905-907,共3页
Chinese Journal of Experimental Surgery
基金
国家重点基础研究发展规划项目(G1 9990 542 0 3)
国家自然科学基金资助项目 (30 1 70 367)
全军十五课题(2 0 0 2 2 0 0 4 )
