NF—κB双链寡脱氧核苷酸圈套对严重肺挫伤兔呼吸功能及炎性因子表达的影响

Effect of nuclear factor-kappa B decoy oligodeoxynucleotides on respiratory function and cytokine expression after severe lung contusion in rabbits

目的研究NF—κB双链寡脱氧核苷酸圈套（NF—κB decoy oligodeoxynucleotides，NF—κB decoy ODN）对严重胸外伤肺挫伤早期呼吸功能及血清炎性因子IL-1β、IL-13表达的影响。方法40只新西兰白兔用随机数字表法分为严重胸外伤肺挫伤组（挫伤组，12只）、严重胸外伤肺挫伤NF—κB杂链decoy ODN治疗组（杂链组，12只）、严重胸外伤肺挫伤NF—κB正链decoy ODN治疗组（正链组，12只）、对照组（正常无损伤组，4只）。建立严重胸外伤肺损伤模型，按实验分组分别将合成的正链、杂链NF—κB decoy ODN经颈内静脉注入，每只实验兔分别注射20μg。于肺挫伤后1，2，3，4h监测呼吸频率、潮气量、气道压力、呼吸流率曲线及呼气末CO2浓度，经颈动脉抽取血标本，ELISA法检测血清炎性因子IL-1β、IL-13的表达。结果肺挫伤后经NF—κB正链decoy ODN治疗后，肺泡通气量、动脉血氧分压、肺顺应性逐渐上升，肺泡一动脉血氧分压差逐渐下降直至接近正常水平，与挫伤组和杂链组比较，差异有统计学意义（P〈0．01）。杂链组上述指标略有变化，但与挫伤组比较，差异无统计学意义（P〉0．01）。血清炎性因子IL-1β在挫伤后1h升至高峰，并持续至实验结束，IL-13的表达在肺挫伤后1h下降，4h降至最低值。经正链decoy ODN治疗后可使挫伤后显著升高的IL-1β明显降低，而IL-13的表达维持于高水平，与挫伤组、杂链组比较，差异有统计学意义（P〈0．01）。结论在严重胸外伤肺挫伤早期呼吸功能出现损害时给予NF—κB正链decoy ODN治疗，对挫伤肺通气功能、换气功能、呼吸力学有明显的保护作用，且血清炎性因子IL-1β的表达减少，IL-13表达升高。

Objective To explore the effect of nuclear factor-kappa B （ NF-κB ） decoy oligodeoxynueleotides （ODN） on respiratory function and expressions of IL-1β and IL-13 in serum following severe lung contusion in rabbits. Methods A total of 40 New-Zealand rabbits were randomly divided into four groups, ie, severe lung contusion group （Group A, n = 12）, severe lung contusion with NF-κB scrambled decoy ODN intervention group （ Group B, n = 12） , severe lung contusion with sense NF- B decoy ODN intervention group （Group C, n = 12） and nomlal control group （Group D, n =4）. After the contusion model was set up, the sense and scrambled NF-κB decoy ODN were infused into the rabbits via the jugular veins in different groups, with 20 g per experimental rabbit. After contusion, respiratory frequency, tidal volume, airway pressure, respiration flow rate curve and end expiration nitric oxide concentration were detected at 1, 2, 3 and 4 hours. The expressions of IL-1β and IL-13 in serum were observed by means of ELISA. Results After sense NF-κB decoy ODN intervention, alveolar ventilation, arterial PO2 and pulmonary compliance were improved, compared with Group A and Group B, with statistical difference （ P 〈 0. 01 ）. The expression of IL-1β was decreased and that of IL-13 increased after sense NF-κB decoy ODN intervention to the severe lung contusion, compared with Groups A and B, with statistical difference （P 〈0.01 ）. The expression of IL-1β was increased to peak level at 1 hour after contusion, which continued to the end of the experiment. While expression of IL-13 was decreased at 1 hour after contusion and reached the minimum level at 4 hours. With intervention with sense decoy ODN, the increased expression of IL-1β was down-regulated, but expression of IL-13 remained at high level, with statistical difference compared with Group A and Group B （ P 〈 0. 01 ）. Conclusions Intervention with sense NF-κB decoy ODN can significantly protect the respiratory function, reduce the expression of IL-1β, and increase expression of IL-13 after severe lung contusion.