地塞米松和山莨菪碱在胸部爆炸伤致急性肺损伤中的防治作用

发布时间：2018-03-05 09:47

本文选题：急性肺损伤　切入点：地塞米松　出处：《中国急救医学》2008年06期 　论文类型：期刊论文

【摘要】：目的利用地塞米松和山莨菪碱在胸部爆炸伤后早期应用,观察p38MAPK、NF-κB p65mRNA表达变化及对炎性细胞因子的影响,探讨地塞米松和山莨菪碱对胸部爆炸伤后急性肺损伤(acute lung injury,ALI)防治作用的机制。方法健康白色家兔78只,随机分为五组:正常对照组(6只);胸部爆炸伤后ALI组(18只),地塞米松治疗组(18只),山莨菪碱治疗组(18只),地塞米松和山莨菪碱联合治疗组(18只)。地塞米松按2mg/kg体质量剂量在致伤后即刻、1、6、12、18h给药;山莨菪碱按1mg/kg体重剂量在相同时间点给药。各实验组再按取材时间分为1、6、24h取材三个亚组。采用8#瞬发电雷管作为爆炸源建立胸部爆炸伤后ALI模型,连续观察呼吸频率、外周动脉压、中心静脉压等生理学指标变化;致伤前及伤后各时间点进行动脉血气分析,计算肺泡-动脉血氧分压差P(A-a)O2;检测血清及支气管肺泡灌洗液中细胞因子TNF-α和IL-6含量变化;原位分子杂交法检测p38MAPK、NF-κB p65mRNA在肺组织的表达情况。结果ALI组伤后1h呼吸频率达最高,为(87±10)次/min,与伤前呼吸频率相比P0.01,后有所下降,但24h后仍未完全恢复至伤前水平(P0.05),而地塞米松和山莨菪碱早期单独或联合应用的各实验组呼吸频率增加情况明显减轻;胸部爆炸伤后ALI组均表现为渐进性的呼吸性酸中毒,氧分压(PaO2)、氧饱和度(SaO2)均明显下降,伤后1h较伤前差异有统计学意义(P0.01),同时表现为肺循环明显的病理分流和无效通气(P(A-a)O2升高),并呈持续恶化趋势;地塞米松和山莨菪碱早期单独或联合应用组PaO2下降明显减轻(P0.05);原位分子杂交检测NF-κB p65、p38MAPK mRNA在肺组织中的表达情况亦可见地塞米松和山莨菪碱单独或联合早期应用的实验组,上述分子在肺组织中的表达明显减少。结论早期应用地塞米松和/或山莨菪碱对NF-κB p65、p38MAPK mRNA在肺组织中的表达下调作用明显增强,从而引起炎性细胞因子含量的下降,减轻"二次肺损伤",对胸部爆炸伤后ALI有较为确实的防治效果。
[Abstract]:Objective to observe the effect of dexamethasone and anisodamine on the expression of p38 MAPKnNF- 魏 B p65 mRNA and its effect on inflammatory cytokines. To investigate the preventive and therapeutic effects of dexamethasone and anisodamine on acute lung injury-induced acute lung injury after thoracic blast injury in 78 healthy white rabbits. They were randomly divided into five groups: normal control group (n = 6), ALI group (n = 18), dexamethasone group (n = 18), anisodamine group (n = 18), dexamethasone group (n = 18) and anisodamine group (n = 18). The mass dose was given for 18 hours immediately after injury. Anisodamine was given at a dose of 1 mg / kg body weight at the same time. Each experimental group was divided into three subgroups according to the time of extraction. The ALI model of chest blast injury was established by using the instantaneous electric detonator as the explosive source, and the respiratory frequency was observed continuously. The changes of peripheral arterial pressure, central venous pressure and so on, arterial blood gas analysis before and after injury, The changes of cytokines TNF- 伪 and IL-6 in serum and bronchoalveolar lavage fluid (BALF) were measured, and the expression of p38MAPKN- 魏 B p65 mRNA in lung tissue was detected by in situ hybridization. Results the respiratory frequency of ALI group was the highest at 1 hour after injury. For 87 卤10 times / min, the respiratory rate decreased after injury compared with that before injury (P 0.01), but still did not return to the pre-injury level (P 0.05) 24 hours later, while the increase of respiratory rate in each experimental group treated with dexamethasone and anisodamine alone or in combination at early stage was significantly reduced. The ALI group showed progressive respiratory acidosis, Pao _ 2 and SAO _ 2 decreased significantly after thoracic blast injury. At 1 hour after injury, the difference was statistically significant (P 0.01) compared with that before injury. At the same time, the pathological shunt of pulmonary circulation and the increase of PMA A / A O 2 were found in the pulmonary circulation, which showed a continuous deterioration trend. In the early stage of dexamethasone and anisodamine alone or in combination group, the decrease of PaO2 was significantly reduced, and the expression of NF- 魏 B p65, p38MAPK mRNA in lung tissue was detected by in situ hybridization, and the experimental group treated with dexamethasone and anisodamine alone or in combination with anisodamine at early stage could also be seen. Conclusion early application of dexamethasone and / or anisodamine can significantly increase the down-regulation of the expression of NF- 魏 B p65 p38 MAPK mRNA in lung tissue, thus causing a decrease in the content of inflammatory cytokines. To reduce secondary lung injury, ALI after chest explosion injury has more definite prevention and treatment effect.
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【分类号】：R82;R655

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