摘要
目的研究干预泛素-蛋白酶体途径对烫伤脓毒症大鼠肺脏核因子-(?)B(NF-(?)B)活化、肿瘤坏死因子-α的产生以及髓过氧化物酶(MPO)活性的影响。方法采用30%TBSAⅢ度烫伤加内毒素攻击大鼠为模型模拟临床烫伤脓毒症,72只Wistar大鼠随机分为正常对照组、烫伤脓毒症组、烫伤脓毒症+蛋白酶体抑制剂N-Acetyl-leucinyl-leucinyl-norleucinal(ALLN)组、烫伤脓毒症+NF-(?)B抑制剂吡咯烷二硫基甲酸酯(Pyrrolidine Dithiocarbamate．PDTC)组,采用凝胶电泳迁移率改变分析法(EMSA)分析肺脏NF-(?)B活性,采用酶联免疫吸附试验检测肺脏TNF-α的变化,采用分光光度法检测肺组织髓过氧化物酶(MPO)的活性。结果肺组织NF-(?)B活性于伤后1h明显增强达到高峰(P＜0．01),伤后2h仍保持较高的活化水平,之后呈逐渐下降趋势。PDTC可明显降低其在伤后1h和2h的活性(P＜0．01),而ALLN可明显降低其在伤后1h的活性(P＜0．01)。PDTC两种抑制剂均可明显降低伤后2h肺组织TNF-α产生,明显降低伤后2h和6h肺组织MPO的活力(P＜0．01)。结论蛋白酶体抑制剂可降低烫伤脓毒症大鼠肺组织NF-(?)B的活性。降低肺组织的炎症反应。
Objective To study the effect of nhiquitin-proteasome pathway inhibition on NF-κB activity and TNF-α secretion as well as myeloperoxidase （MPO） activity in the lung of rats with posthurn sepsis. Methods Rats with 30% total body surface area （TBSA） scald burn were injected lipopolysaceharide （LPS） into intraperitoneal to produce posthurn sepsis. Seventy two Wistar rats were randomly divided into normal control group, posthurn sepsis group, proteaseme inhibitor N-Aeetyl-leueinyl-leueinyl-norleucinal （ALLN） treatment group and NF-κB inhibitor Pyrrolidine Dithiocarbamate （PDTC） treatment group. NF-κB activation, tumor necrosis factor-α （TNF-α） protein expression, and pulmonary MPO activity were determined by electrophoretie mobility shift assay, enzyme-linked immunoserbent assay （ELISA）, and speetrophotometrie method, respectively. Results NF-κB activity was markedly activated and reached its peak at lh after burn and still kept high at 2 hours and then gradually reduced （ P 〈 0.01 ）. PDTC markedly decreased NF-κB activity at 1 h and 2 h after burn （ P 〈 0.01 ）, while ALLN markedly decreased NF-κB activity at 1 h （ P 〈 0.01 ） but not at 2 h. TNF-α secretion was decreased at 2 hours after the administration of ALLN or PDTC in the lung （ P 〈 0.01 ）. Pulmonary MPO activity was significantly elevated at 2 h and 6 h （ P 〈 0.01 ）, but pretreatment with PDTC or ALLN markedly decreased the MPO activity at 2 h and 6 h （ P 〈 0.01 ）. Conclusion Eearly treatment with inhibitor of ubiquitinproteasome pathway might decrease the NF-κB activity and inflammatory reaction in the lung of rats with posthurn sepsis.
出处
《中华急诊医学杂志》
CAS
CSCD
2006年第10期886-889,共4页
Chinese Journal of Emergency Medicine
基金
国家自然科学基金面上项目(30571919
30271339)
