右美托咪定对单肺通气所致肺损伤的保护作用研究

发布时间：2018-05-11 15:34

本文选题：单肺通气 + 右美托咪定　；参考：《河南大学》2014年硕士论文

【摘要】：背景单肺通气(one-lung ventilation, OLV)是现代胸外科手术麻醉中比较常用的呼吸管理方法，然而这种非生理性的通气方式会引起急性肺损伤(acute lung injury, ALI)。在单肺通气(OLV)过程中，患者开胸侧肺脏完全萎陷，造成肺内血液分流及通气血流比值降低。同时低通气状态的时候可造成细胞的缺血和缺氧性的破坏与损伤，然而缺氧组织在恢复了血液供应后却有可能进一步加剧细胞的损伤。炎性细胞因子、氧自由基和中性粒细胞相互作用在这个缺血再灌注损伤过程中扮演了十分重要的角色。肺不张时肺血管会发生缺氧性的反应性收缩，而肺复张过程中，随着氧气通过气道进入终末肺组织，又可造成反应性肺血管扩张。进而导致血管壁损伤大量的氧自由基被释放进入血液中。因为氧自由基包含一个未成对电子的外层电子轨道基，它们的化学性质非常活泼，易攻击细胞内的大分子物质。在正常的生理情况下，体内内源性抗氧化系统能够及时地清除生成过多的氧自由基。然而在病理条件下，由于活性氧自由基产生过多，不能被及时清除，平衡被打破，引发了剧烈的氧化应激反应，导致细胞功能障碍。再加上手术造成的机械刺激，会导致肺部的炎性反应，诱发或加重肺损伤。多年来，大多数研究都集中于保护性肺通气策略的研究，这对临床单肺通气技术的进展有很大的贡献。然而，目前对于单肺通气造成肺部损伤的保护性药物的研究较少。右美托咪锭(dexmedetomidine, DEX)为α受体激动剂，它可以高选择性地与α2受体结合，具有镇静、镇痛、抗焦虑、抗炎性反应和良好的交感神经抑制作用。DEX最初是被作为镇静药物使用，后逐渐被推广用于麻醉辅助用药。本研究中，首先通过回顾性研究方法探讨单肺通气引起肺损伤时的氧自由基所介导的氧化应激作用，进而通过动物实验前瞻性研究右美托咪定对单肺通气引起的急性肺损伤的保护作用。目的研究在单肺通气(one-lung ventilation，OLV)情况下，氧自由基介导的氧化应激反应，并通过动物实验以评估单肺通气时右美托咪定对肺损伤的保护性作用。方法 1.临床研究：在单肺通气(OLV)情况下氧自由基所介导的氧化应激反应。从2010年到2013年，调查了221名（非小细胞肺癌）患者研究单肺通气引起肺损伤的发生机制。这221名患者被分成六组。A组，在非OLV条件下肺叶切除术组；B组，在OLV条件下全肺切除组；C、D、E在OLV条件下时长分别为60、90和120分钟的肺叶切除术组；F为健康对照组。分别在术前、术中及术后抽取血液标本。并测定血清丙二醛(MDA)含量。对MDA含量进行组间和组内分析。 2.动物实验：将30只雄性新西兰大白兔随机选取10只作为假手术组（空白对照组），只进行穿刺和插管并不进行单肺通气。另外两组一组为单纯的单肺通气组，另外一组为单肺通气加右美托咪定。通过检测TNF-α、IL-6这两种因子在三组实验中的差别估测右美托咪定对单肺通气的保护作用。结果 1.临床研究结果 C-E组，即OLV肺叶切除术组的患者血清MDA水平明显高于（P0.001）其他实验组，而且这一效应一直持续至术后12小时。患者所产生的氧化应激的反应程度与其OLV的时长是相关的，，（EDC，P值均0.001）。行全肺切除术的B组因完全切除肿瘤细胞可能浸润的肺组织后，患者血清MDA含量较A组更低（P0.001）。健康对照组（F组）的血清MDA平均值为1.28±0.6nmol/ml。肺癌患者的血清MDA的浓度介于5.85±4.1nmol/ml到5.90±3.8nmol/ml之间。统计分析结果显示，F1与A1-G1比较差异有统计学意义（P0.001），而A1-E1之间无显著性差异。A，B组病例表明在开胸肺切除术MDA水平有明显的升高。MDA增长的峰值出现在术中。对每组而言这种增长均有统计学意义（P0.001）。术后A组MDA水平呈逐渐下降的趋势（A3-A8）。相反在B组，MDA下降却很剧烈，从术前5.89±4.2nmol/ml到术中6.44±3.7nmol/ml（P0.001）再到术后1小时4.89±4.6nmol/ml（P0.001）。结果表明单侧肺通气显著加剧了氧化应激反应。 C-E组显示了相同的趋势。术前MDA水平轻度升高。比较A2-E2并没有显著性差异。但OLV结束后5分钟内，MDA水平则上升了1倍还多。在C组，从单肺通气期间6.43±3.5nmol/ml增至膨肺时的14.45±4.8nmol/ml（P0.001）。在D组，从6.43±4.3nmol/ml到15.5±4.1nmol/ml（P0.001）。在E组，从6.39±0.8nmol/ml到18.36±4.0nmol/ml（P0.001）。血清MDA升高水平与肺不张的持续时间相关。E3显著高于D3（P0.001），D3显著高于C3（P0.001）。单肺通气的时间越长，氧化应激反应的也就越强烈。这一效应可持续至术后1小时。在所有各组中，氧化应激反应在术后6小时逐渐消退。全肺切除术的B组表现最为显著（B4比C4-E4，P0.001）。此外，与F组比较发现，恶性肿瘤本身也可诱发脂质过氧化反应，观察发现切除肿瘤后48小时内MDA含量迅速下降（A1-E1比A8-E8P0.001）。这与是否采用单肺通气无关。 2.动物实验结果通过免疫印迹检测以及部分炎症因子、组化结果，表明右美托咪定可以有效的对肺脏起到保护作用。结论 1、单肺通气会造成萎陷肺的组织病理损伤、以及肺炎症反应增加。 2、右美托咪定使大白兔实验组TNF-α、IL-6表达量减少，说明右美托咪定可以减少肺部炎症反应，对单肺通气时的缺血再灌注损伤有一定的保护作用。。 3、右美托咪定使大白兔实验组降低了机体氧化应激程度，减轻了肺组织缺血再灌输损伤，对肺组织起到了保护作用。
[Abstract]:Background

One - lung ventilation ( OLV ) is a commonly used respiratory management method in modern thoracic surgery anesthesia , but this non - physiologic ventilation can cause acute lung injury ( ALI ) . In the course of single lung ventilation ( OLV ) , the pulmonary blood flow and the ratio of ventilation and blood flow in the lung of the patient are reduced . At the same time , the oxygen free radicals can be destroyed and damaged during ischemia / reperfusion injury . However , in normal physiological condition , the endogenous antioxidant system can eliminate the excessive oxygen radicals in time .

For many years , most studies have focused on protective lung ventilation strategies , which contribute significantly to the development of clinical single - lung ventilation . However , the current study of protective drugs that cause lung injury to single - lung ventilation is less . dexlansoprazole ( DEX ) is an alpha - receptor agonist , which can be selectively combined with alpha2 receptors with sedation , analgesia , anti - anxiety , anti - inflammatory responses , and good sympathetic nerves . DEX is initially used as a sedative drug and is gradually extended to anesthesia - assisted medication .

In this study , the oxidative stress mediated by oxygen free radicals in lung injury induced by single lung ventilation was investigated by retrospective study .

Purpose

In the case of one - lung ventilation ( OLV ) , oxygen - free radical - mediated oxidative stress reaction was studied , and the protective effect on lung injury was assessed by animal experiments .

method

1 . Clinical study : Oxidative stress mediated by oxygen free radicals in the case of single lung ventilation ( OLV ) .

From 2010 to 2013 , 221 patients ( non - small cell lung cancer ) were investigated to investigate the mechanism of lung injury . 221 patients were divided into six groups .
group B , total lung resection group under OLV condition ;
C , D and E were 60 , 90 and 120 min respectively under OLV condition .
F was the healthy control group . Blood samples were taken from the blood samples before and after operation , and the content of MDA in serum was measured . The content of MDA was analyzed in the group and group .

2 . Animal experiment : 30 male New Zealand white rabbits were randomly selected as sham operation group ( blank control group ) , only puncture and intubation were performed without single lung ventilation .

Results

1 . Clinical Study Results

In group C - E , the level of serum MDA in patients with OLV was significantly higher than that in other experimental groups ( P 0.001 ) , and the effect lasted until 12 hours after operation . The degree of reaction of oxidative stress produced by patients was related to the duration of OLV , ( EDC , P = 0.001 ) . The level of MDA in patients with lung cancer was 5.85 卤 4.1nmol / ml and 5.90 卤 3.8nmol / ml .

The results showed that unilateral lung ventilation significantly increased the reaction of oxidative stress . There was no significant difference in MDA level in group C , from 6.43 卤 3.5nmol / ml to 14.45 卤 4.8nmol / ml ( P0.001 ) . In group D , the level of MDA increased from 6.43 卤 4.3nmol / ml to 18.36 卤 4.0nmol / ml ( P0.001 ) .

In all groups , the oxidative stress reaction gradually disappeared in 6 hours after operation , and the B group of total lung resection was the most significant ( B4 vs C4 - E4 , P0.001 ) . In addition , compared with group F , malignant tumor itself could induce lipid peroxidation , and the content of MDA decreased rapidly in 48 hours after resection of tumor ( A1 - E1 ratio A8 - E8P0.01 ) . This was not related to whether single lung ventilation was adopted .

2 . Animal experiment results

By Western blot and partial inflammatory factors , the results of the group showed that dexlansoprazole could effectively protect the lungs .

Conclusion

1 . The single - lung ventilation can cause pathological damage of the tissues of the lung and increase the inflammatory response of the lung .

2 . The amount of TNF - 伪 and IL - 6 in the experimental group of rabbits was decreased , and the expression of TNF - 伪 and IL - 6 in experimental group was decreased .

3 . The experimental group reduced the degree of oxidative stress in the experimental group of rabbits , alleviated the injury of lung tissue ischemia and reperfusion , and played a protective role in the lung tissue .

【学位授予单位】：河南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614

【共引文献】