摘要
目的从组织受体水平探讨核因子-κB（NF-κB）及其抑制剂在创伤失血性休克过程中肝损伤与抗损伤中的作用机制。方法采用双侧股骨骨折伴失血性休克模型,并对NF-κB进行抑制后再致伤。NF-κB抑制剂采用二硫代氨基甲酸吡咯烷（PDTC）腹腔注射。动态观察伤后8 h大鼠肝组织NF-κB、肝脏病理、肝功能、TNF-α、IL-6等变化。肝组织NF-κB采用凝胶迁移试验（EMSA）法测定结合活性。TNF-α、IL-6通过酶联免疫吸附分析（ELISA）检测。结果NF-κB的活性伤后迅速升高,伤后2 h即与正常对照相比差异有统计学意义,伤后6 h达到高峰,伤后8 h仍维持较高水平;TNF-α、IL-6伤后逐渐升高,并于伤后6 h达到高峰,休克后8 h仍维持较高水平;光镜下伤后4-8 h肝窦内淤血明显,有大量炎性细胞浸润;血清ALT、TB伤后4 h开始增高,6-8 h达到峰值。抑制NF-κB再致伤后,TNF-α、IL-6伤后各个时相点均迅速回落;肝脏大体淤血、肿胀明显减轻;光镜下伤后4-8 h可见肝小叶排列基本正常,肝细胞变性明显好转,肝窦内见淤血减轻,仅见少许淋巴细胞及中性粒细胞浸润;血清ALT、TB明显下降,与未抑制组相比差异有统计学意义。结论NF-κB参与了严重创伤失血性休克后肝损伤的发生,NF-κB增高越多,肝损害越重,抑制NF-κB的活性有助于减轻创伤失血性后肝脏的急性损害,提示NF-κB及其抑制剂在严重创伤休克后肝组织细胞损伤与抗损伤机制方面起着重要作用。
Objective To investigate changes and functions of nuclear factor kappa B （ NF -κB ） and its suppressive agent at the level of tissue cell receptor in liver injury after trauma with hemorrhagic shock. Methods Adult Wistar rats were used and rats model was produced by adopting hemorrhagic shock in accompany with bilateral femur fracture, and Inhibiting the activity of NF -κB before trauma with hemorrhagic shock, Pyrrolidine dithiocarbamate （ PDTC ） was used by intraperitoneal injection. Changes of hepatic tissue NF -κB, pathology of liver, hepatic function markers, TNF -α and IL - 6 were dynamically observed. The expression of NF -κB in hepatic tissue was assayed by electrophoretic mobility shift as- say, and then analyzed with computer imaging system. The contents of cytokines of TNF -α and IL - 6 in the liver tissue were detected by ELISA. Results Activity of NF -κB gradually increased in hepatic tissue after trauma, was obviously advanced than normal control at 2 h after trauma, heightened to the peak at 6h after trauma in hemorrhagic shock, and maintained rather high lever at 8 h after trauma, TNF -α and IL -6 gradually increased, and maintained high lever at 8 h after trauma. Hepatic congestion was obvious,there were much inflammatory cells infiltrated in hepatic sinusoid at 4-8 h after trauma with hemorrhagic shock. ALT and TB increased at 4 h after trauma. Inhibiting the activity of NF -κB before trauma with hemorrhagic shock, hepatic congestion was lessen, the arrangement of hepatic lobules was basicly nomal, hepatic cell degeneration was improved. A little homeocyte and neutrophile granulocyte were obversed in sinus hepaticus. The contents of cytokines of TNF -α and IL - 6 in the liver tissue were droped, and ALT and TB were descent. Conclusions NF -κB might participate in the course of hepatic injury after trauma with hemorrhagic shock. The higher Activity of NF -κB is relation with severe liver injury. Inhibiting the activity of NF -κB could weaken the hepatocyte injury and have prot
出处
《中国急救医学》
CAS
CSCD
北大核心
2008年第4期335-338,共4页
Chinese Journal of Critical Care Medicine
基金
重庆市自然科学基金项目(No.2004-BB5068)
