产兔与非孕兔休克复苏后肺损伤的比较研究

The lung injury in postpartum and non-pregnant rabbits after resuscitation from hemorrhagic shock

目的探讨产兔和非孕兔失血性休克复苏后急性肺损伤的差异。方法将18只新西兰兔按随机数字表法分为产兔组和非孕兔组，每组9只。采用颈动脉放血致失血性休克1h，乳酸林格液复苏持续3h建立失血性休克复苏模型。分别于产前期、产后期（休克前期，0h）、休克期末（1h）、复苏期间（2．5h）以及复苏期末（4h）5个时间点采血测定肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）；复苏期持续3h后处死动物，取肺组织检测丙二醛（MDA）、超氧化物歧化酶（SOD）、髓过氧化物酶（MP0）、干／湿重比值（D／W），以及核转录因子-κB（NF—κB）活性和细胞间黏附分子-1（ICAM-1）mRNA表达。结果产兔产前期血清TNF-α（ng／L）、IL-10（ng／L）含量与非孕兔差异无统计学意义（TNF-α：87．6±6．8比83．2±5．3；IL-10：44．9±3．9比42．7±3．4，均P〉0．05）；休克前期TNF-α水平显著增高（102．5±8．1比87．6±6．8，P〈0．05）。产兔与非孕兔休克1h后TNF-1α、IL-10均升高；各复苏时期产兔TNF-α水平明显高于非孕兔（1h：230．0±14．9比202．0±10．1，2．5h：290．0±18．6比236．0±14．4，4h：265．0±15．9比217．0±12．8，均P〈0．05），而IL-10水平明显低于非孕兔（1h：104．3±6．9比135．0±7．8，2．5h：146．8±9．4比178．3±11．7，4h：126．0±7．9比165．8±9．6，均P〈0．05）。休克复苏后产兔肺组织MDA、MPO、D／w比值、NF-κB活性和ICAM-1mRNA表达均显著高于非孕兔（MDA（nmol／mg）：52．6±5．9比39．4±4．7，MPO（U／rag）：4．62±0．85比3．26±0．62，D／W比值：0．186±0．025比0．143±0．016，NF-κB（A值）：0．89±0．27比0．46±0．15，ICAM-1mRNA：4．6±1．2比2．5±0．7，均P〈0．053；而SOD（U／mg）水平较低（47．8±6．7比63．5±8．2，P〈0．05）。结论分娩可致产兔血清炎症因子TNF-α显著升高，失血性休克复苏后产兔出现肺组织炎症损伤较非孕兔更为严重，炎症因子的差异可能是导致休克复苏后炎症应答差异的原因之一。

Objective To investigate the difference in the development of acute lung injury after hemorrhagic shock in postpartum and non-pregnant rabbits. Methods Hemorrhagic shock/resuscitation was produced on 9 pregnant New-Zealand rabbits postpartum （within 24 hours after giving birth） and 9 nonpregnant controls via carotid artery bleeding and perfusion （i. v. ） of lactate Ringer solution for 3 hours. The serum level of cytokine tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） in the animals were measured at different time points. Lung tissue were taken 3 hours after resuscitation for the determination of malondialdehyde （MDA）,the activity of superoxide dismutase （SOD）, myeloperoxidase （MPO）, dry/wet weight （D/W）, nuclear factor-κB （NF-κB）, and mRNA content of intercellular adhesion molecule-1 （ICAM-1）. Results Serum TNF-α （ng/L） and IL-10 （ng/L） in antepartum pregnant rabbits were not significantly different from non-pregnant rabbits （TNF-α 87.6±6.8 vs. 83.2±5.3; IL-10： 44. 9±3.9 vs. 42.7 ± 3.4, both P〈0. 05）. However, the serum TNF-α increased significantly after delivery （102.5 ±8. 1 vs. 87. 6±6.8, P〈0. 05）. TNF-α and IL-10 increased 1 hour after shock in both postpartum and nonpregnant rabbits. The serum TNF-α in postpartum rabbits was significant higher than non-pregnant rabbits in each resuscitation period （1 hour： 230.0±14. 9 vs. 202.0±10. 1, 2.5 hours： 290. 0±18.6 vs. 236.0± 14.4, 4 hours. 265.0 ± 15.9 vs. 217.0 ±12.8, all P〈0.05）, meanwhile the serum IL-10 in postpartum animals was significantly lower than the non-pregnant controls （1 hour： 104. 3 ± 6.9 vs. 135.0 ± 7.8, 2.5 hours.. 146.8±9.4 vs. 178. 3±11.7, 4 hours： 126.0±7.9 vs. 165.8±9.6, all P〈0. 05）. The value of MDA, MPO, D/W, NF-κB activity and ICAM-1 mRNA content in lung tissue of postpartum rabbits were all significant higher than non-pregnant rabbits after resuscitation （MDA （nmol/mg）： 52.6±5.9 vs. 39.4d： 4.7, MPO （U/rag） ： 4.62±0. 85 vs. 3.26±0.62, D/W： 0. 186±0. 025 vs. 0. 143：k0. 016, NF-κB activity （Avalue）： 0.89±0.27 vs. 0.46±0.15, ICAM-1 mRNA： 4.±1. 2vs. 2.5±0.7, allP〈0.05], but the activity of SOD （U/mg） was lower （47.8± 6.7 vs. 63.5±8. 2, P〈0.05） in the controls after resucitation. Conclusions Delivery causes significant increase in serum TNF-α in pregnant rabbits. Inflammatory lung injury is more severe in postpartum rabbits after resuscitation from hemorrhagic shock, and the increased serum level of inflammatory mediators may be part of the mechanism for such difference.