中文摘要：

目的 探讨烧伤后p38丝裂原活化蛋白激酶（MAPK）信号转导通路和核因子（NF）-κB／抑制因子（I）KB通路在调控细胞因子产生方面的地位及是否存在相互作用。方法 人单核细胞株THP-1分为正常血清对照组、烧伤血清组、烧伤血清＋SB203580组（p38MAPK特异性抑制剂）和烧伤血清＋PDTC（NF-κB特异性抑制剂）组，每组均实验8次。血清刺激24h后，酶联免疫吸附法测定上清液中肿瘤坏死因子仪（TNF-α）和白细胞介素1β（IL-1β）的含量，蛋白印迹（Western blot）法检测THP-1内p38MAPK的活性和IKBet的表达，凝胶电泳迁移率变化分析法检测THP-1内NF-κB和激活蛋白（AP-1）活性的变化。结果 和正常血清相比，烧伤血清刺激后24h，THP-1上清液中TNF-α和IL-1β的含量均明显上升[分别为（7．30±0．84）ng／ml和（2．20±0．28）ng／ml，P〈0．05；（2．88±0．38）ng／ml和（O．81±0．14）ng／ml，P〈0．05]，p38MAPK活性升高（4728±582和1291±163，P〈0．05），IKBct含量下降（1211±115和2658±318，P〈0．05），THP-1中NF-κB活性和AP-1活性均较正常血清显著升高（1636±170和317±32，P〈0．05；946±137和361±40，P〈0．05），使用SB203580和PDTC均能抑制烧伤血清刺激后THP-1上清液中TNF-α和IL-1β的含量的上升。预先给予SB203580能抑制烧伤血清刺激后THP-1中p38MAPK和AP-1活性升高，但对IκBα含量和NF-κB活性无显著影响；预先给予PDTC可以防止烧伤血清刺激后THP-1中IκBα含量的下降和NF-κB活性的升高，而对p38MAPK和AP-1活性无影响。结论 在烧伤后全身炎症反应的发生中，p38MAPK信号转导通路和NF-κB／IKB通路是两个平行和独立的信号转导通路，彼此之间没有直接的联系，共同调节着烧伤后单核细胞TNF-α和IL-1B的产生。

英文摘要：

Objective To investigate the interaction between p38 mitogen-activated protein kinase signal transduction pathway and nuclear factor （NF）-κB/IKB system on the proinflammatory cytokines release after burn trauma. Methods Human monocyte line THP-1 were incubated with serum from eight healthy controls, burn sera, burn sera pretreatment with SB203580, and burn sera pretreatment with pyrrolidine dithiocarbamate （PDTC）. After 24 hours incubation with serum, tumor necrosis factor （TNF）-α and interleukin-1β （IL-1β） levels in THP-1 culture supernatants were measured by ELISA. The activities of p38 MAPK and expressions of IKBet in THP-1 were measured by Western blot analysis. The EMSA method was used to characterize the binding activities of NF-κB and activating protein （AP） -1 in THP-1. Results In comparison with normal controls, burn sera resulted in a significant higher level release of TNF-α and IL- 1β in THP-1 [ （7. 30±0. 84） ng/ml vs （2. 20±0. 28） ng/ml,P 〈0. 05;（2. 88±0. 38） ng/ml vs（0. 81 ± 0. 14 ） ng/ml ,P 〈 0. 05 ] , which were significantly inhibited by pretreatment with SB203580 or PDTC. Burn sera showed increased activities of p38 MAPK and AP-1 in THP-1 （4728 ±582 vs 1291 ± 163, P 〈 0. 05 ; 946± 137 vs 361 ±40,P 〈0.05）, which were abolished by pretreatment with SB203580 but not PDTC. The expression of IκBα in THP-1 incubated with burn sera was significantly decreased than those incubated with control sera （1211 ± 115 vs 2658 ± 318, P 〈 0. 05 ）, which were abolished by pretreatment with PDTC but not SB203580. Burn sera also leaded to an increased activity of NF-~B in THP-1 （1636 ＋ 170 vs 317 ＋ 32, P 〈 0. 05）, which were abolished by pretreatment with PDTC but not SB203580. Conclusions There are no direct interaction between p38 MAPK signal transduction pathway and NF-κB/IκB pathway. These two pathways, which regulate the production of TNF-α and IL-1β in monocyte following burn trauma, are parallel and independent.