核因子-κB“圈套”策略对创伤性炎症大鼠肝脏损伤的抑制作用  

Effects of decoy strategy targeted to NF-κB on trauma-associated liver inflammation in rats

作　　者：杨文军[1] 陈云志[1] 万丽[2] 张虎祥[2] 孙运鹏[1] 陶崇林[1] 陈宗静[1] 宋其同[1] 余正平[1] 张启瑜[1] 

机构地区：[1]温州医学院附属第一医院肝胆外科,325000 [2]温州医学院附属第一医院病理科,325000

出　　处：《中华普通外科杂志》2009年第7期582-586,共5页Chinese Journal of General Surgery

摘　　要：目的探讨核因子-κB“圈套”策略对创伤性炎症大鼠肝脏损伤的抑制作用。方法Wistar大鼠108只，随机分成对照组、创伤性炎症组和“圈套”ODN组，各组动物分别于术后3、6、12、24、48和72h分批处死。检测血浆转氨酶的水平，在光镜下观察肝细胞损伤程度。运用凝胶阻滞实验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。检测大鼠肝脏组织TNF-α和IL-6的mRNA及蛋白水平。结果大鼠创伤性炎症术后3h肝脏NF-κB的活性开始升高，术后12h达高峰。肝脏组织TNF-α和IL-6mRNA和蛋白表达明显上升，血浆转氨酶含量也明显上升，肝细胞变性坏死，肝小叶结构破坏明显。“圈套”ODN治疗后大鼠肝脏组织TNF-α和IL-6的mRNA和蛋白表达均明显下降，血浆转氨酶水平明显下降，光镜下肝小叶结构损伤明显好转。结论NF-κB靶向性“圈套”ODN通过特异性抑制NF-κB活性，可以有效地抑制创伤性炎症大鼠肝脏炎症介质TNF-α和IL-6的释放，从而明显改善肝脏结构和功能的损伤。Objective To study the effects of decoy strategy targeted to NF-κB on the development of trauma-associated liver inflammation in rats. Methods In this study, 108 Wistar rats were randomized into 3 groups： control group, traumatic inflammation group and traumatic inflammation plus decoy ODN group. Rats were sacrificed on 3,6,12,24,48 and 72hrs in each group respectively. Liver functions and structural changes were examined and compared between the groups. DNA binding activity of NF-KB in liver tissue was measured by EMSA. TNF-α and IL-6 gene expressin in liver tissue was assessed by RT-PCR and TNF-α and IL-6 protein level was determined by ELISA. Results The DNA binding activity of NF-KB in liver rose at 3 hours after induction of liver inflammation following trauma and peaked at 12 hours. Correspondingly, both the mRNA and protein levels of TNF-α and IL-6 elevated significantly, as well as the serum alanine amiuotransferase level culminating at 2d hours after surgery. Hepatocytes was edematous, degeneration and necrosis, with dramatic destruction of lobular structures. All these changes were significantly inhibited with NF-KB decoy oligodeoxynucleotides. Conclusions Decoy oligodeoxynucleotides specifically inhibit the activity of NF-κB, and the release of pro-inflammatory cytokines, TNF-α and IL-6 release from the liver in response to traumatic inflammation decrease, hence the injury on fiver structures and functions were alleviated.

关 键 词：创伤与损伤 炎症介导素类 动物 实验 

分 类 号：R686[医药卫生—骨科学]