摘要目的:观察胸腔热灌注(IHP)对兔急性肺损伤(ALI)中Toll样受体4(TLR4)/核转录因子(NF-κB)/p38丝裂原活化蛋白激酶(p38MAPK)炎症信号通路的影响。方法:新西兰大白兔31只，按随机数字表法分为4组，假撞击组(A组，7只)、胸部撞击组(B组，8只)、撞击+35 ℃常温灌注组(C组，8只)和撞击+43 ℃度热灌注组(D组，8只)，垂直撞击兔右侧胸部，建立ALI模型行IHP，酶联免疫吸附试验(ELISA)法检测肺组织中热休克蛋白70(HSP70)及肺泡灌洗液中白细胞介素(IL)-1、IL-6、肿瘤坏死因子(TNF-α)的含量。荧光定量PCR技术检测肺组织中NF-κB、p38MAPK、TLR4。蛋白质印迹法(Western blot)检测肺组织p-ATF2、磷酸化蛋白p38(p-p38)蛋白表达情况，并进行组间比较，组间比较采用 t检验。 结果:IHP12 h后，D组的HSP70(17.40±2.30)高于A组(5.30±2.40)、B组(6.10±2.10)、C组(6.20±2.60)，差异有统计学意义( t＝9.126、10.262、9.963， P<0.05)。D组NF-κB的mRNA(2.74±0.10)高于A组(0.73±0.13)、B组(1.85±0.07)、C组(1.41±0.28)，差异有统计学意义( t＝33.823、20.623、12.652， P<0.05)。D组p38MAPK的mRNA(2.49±0.23)高于A组(0.39±0.12)、B组(1.43±0.16)、C组(1.25±0.08)，差异有统计学意义( t＝21.648、10.701、14.403， P<0.05)。D组TLR4的mRNA(3.41±0.32)高于A组(0.56±0.18)、B组(2.32±0.18)、C组(1.73±0.11)，差异有统计学意义( t＝22.347、8.397、14.043， P<0.05)。D组磷酸化活化转录因子2(p-ATF2)的蛋白灰度值(1.04±0.12)高于A组(0.48±0.11)、C组(0.65±0.08)，差异有统计学意义( t＝9.369、7.649， P<0.05)。D组p-p38的蛋白灰度值(0.79±0.13)高于A组(0.37±0.09)、C组(0.53±0.07)，差异有统计学意义( t＝7.162、4.981， P<0.05)。D组的TNF-α(50.30±7.70)低于B组(94.40±5.80)和C组(79.60±8.40)，差异有统计学意义( t＝-12.939、-7.273， P<0.05)。D组的IL-1(63.40±9.70)低于B组(135.70±6.80)和C组(103.20±8.40)，差异有统计学意义( t＝-17.263、-8.773， P<0.05)。D组的IL-6(34.20±3.70)低于B组(78.40±2.90)和C组(56.70±2.80)，差异有统计学意义( t＝-26.593、-13.715， P<0.05)。 结论:胸腔热灌注通过TLR4/NF-κB/p38MAPK信号通路的高表达，对炎症反应具有抑制作用。

abstractsObjective:To observe the effect of pleural intrapleural hyperthermic perfusion (IHP) on inflammatory signal pathway toll like receptor 4 (TLR4)/nuclear transcription (NF-κB)/p38 mitogen-activated protein kinase (p38MAPK) in rabbits with acute lung injury (ALI).Methods:Totally, 31 New Zealand white rabbits were randomly divided into sham impact group (A, n=7), chest impact group (B, n=8), impact + 35 ℃ lavage group (C, n=8) and impact + 43℃ heat perfusion group (D, n=8). The rabbit model of ALI was established. The levels of heat shock protein 70 (HSP70) in lung tissue and interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). TLR4/NF-κB/p38MAPK in lung tissue was detected by quantitative real-time PCR. The protein expression of p-ATF2 and p-p38 in lung tissues was detected by Western blotting and compared between groups. Results:After 12 h of IHP, the HSP70 (17.40±2.30) in group D was significantly higher than that in group A (5.30±2.40), group B (6.10±2.10), and group C (6.20±2.60). The difference was statistically significant ( t=9.126, 10.262, 9.963, P<0.05). The mRNA expression of NF-κB in group D (2.74±0.10) was significantly higher than that in group A (0.73±0.13), group B (1.85±0.07), and group C (1.41±0.28, t=33.823, 20.623, 12.652, P<0.05). The mRNA expression of p38MAPK in group D (2.49±0.23) was significantly higher than that in group A (0.39±0.12), group B (1.43±0.16), and group C (1.25±0.08, t=21.648, 10.701, 14.403, P<0.05). The mRNA expression of TLR4 in group D (3.41±0.32) was significantly higher than that in group A (0.56±0.18), group B (2.32±0.18), and group C (1.73±0.11, t=22.347, 8.397, 14.043, P<0.05). The protein gray value of p-ATF2 in group D (1.04±0.12) was significantly higher than that in group A (0.48±0.11) and group C (0.65±0.08, t=9.369, 7.649, P<0.05). The protein gray value of p-p38 in group D (0.79±0.13) was significantly higher than that in group A (0.37±0.09) and group C (0.53±0.07, t=7.162, 4.981, P<0.05). The TNF-α in group D (50.30±7.70) was significantly lower than that in group B (94.40±5.80) and group C (79.60±8.40, t=-12.939, 7.273, P<0.05). The IL-1 in group D (63.40±9.70) was significantly lower than that in group B (135.70±6.80) and group C (103.20±8.40, t=-17.263, 8.773, P<0.05). The IL-6 in group D (34.20±3.70) was significantly lower than that in group B (78.40±2.90) and group C (56.70±2.80, t=-26.593, 13.715, P<0.05). Conclusion:Thoracic heat perfusion regulated the high expression of TLR4/NF-κB/p38 MAPK signaling pathway, which had an inhibitory effect on inflammatory responses.