右美托咪定对高原环境暴露后失血性休克大鼠肺水肿的保护作用

Protective effect of dexmedetomidine on pulmonary edema with hemorrhagic shock in rats exposed to plateau environment

目的探究右美托咪定对高原环境暴露后失血性休克大鼠肺水肿的保护作用。方法280只10周龄SD雄鼠(体质量180~220 g)随机均分为高原对(Sham)照组、高原环境暴露后失血性休克(HS)组、乳酸林格复苏(LR)组以及右美托咪定+乳酸林格复苏(DEX+LR)组。使用低压缺氧舱模拟5000 m海拔,大鼠进舱接受48 h预处理,出舱后立即经尾静脉注入油酸处理,油酸诱导0.5 h后,经股动脉缓慢抽血至全身血量的40%~50%,建立高原环境暴露后失血性休克模型。预防性给予右美托咪定后,通过肺含水量、肺微血管通透性、肺泡灌洗液蛋白浓度的变化,观察右美托咪定对肺血管通透性的影响;通过测定呼吸频率、潮气量等指标,观察右美托咪定对呼吸功能的作用;通过HE染色观察肺组织病理变化;通过血气分析观察右美托咪定对动脉血气的影响和右美托咪定对存活率的影响。结果与Sham组比较,HS组大鼠肺含水量、肺微血管通透性、肺泡灌洗液蛋白浓度升高(P<0.05),呼吸频率上升(P<0.05),潮气量、分钟通气量下降(P<0.05)。HS组HE染色结果显示,其肺泡壁增厚,肺泡腔部分缩小,腔内少许渗出,肺泡壁伴有炎性细胞浸润。HS组动脉血气结果提示酸中毒,大鼠处于缺氧状态(P<0.05)。与HS组比较,LR组大鼠肺水肿加重,HE染色结果显示肺泡囊融合、肺组织结构破坏、炎性细胞浸润明显;呼吸频率、潮气量上升,且动脉血气进一步恶化(P<0.05)。右美托咪定可显著改善高原环境暴露后失血性休克肺水肿大鼠的肺功能,与LR组比较,DEX+LR组大鼠肺微血管通透性、肺含水量、肺泡灌洗液蛋白浓度降低(P<0.05),大鼠潮气量、呼吸频率、分钟通气量趋于Sham组(P<0.05),HE染色结果显示肺泡结构趋于完整,肺泡腔内渗出减少甚至消失;动脉血气分析提示酸中毒改善(P<0.05),最终提高存活率。结论高原环境暴露后失血性休克大鼠在常规复苏时更容易诱发或加重肺水肿,预防性给与右美托咪定(10μg/kg)能够有效预防肺水肿的发生。

ObjectiveTo investigate the protective effect of dexmedetomidine on pulmonary edema in rats with hemorrhagic shock after exposure to a plateau environment.MethodsA total of 280 SD male rats(10 weeks old,200~220 g)were randomly divided into 4 groups:the plateau control(sham)group,the hemorrhagic shock after exposure to the plateau environment(HS)group,the lactated Ringer’s resuscitation(LR)group,and the dexmedetomidine+lactated Ringer’s resuscitation(DEX+LR)group.Using a low-pressure hypoxic chamber to simulate 5000 m altitude,the rats have stayed the chamber for 48 h to accept pretreatment,injecting oleic acid treatment via the tail vein.After 0.5 h of induction of oleic acid,the rats were slowly drawn blood via the femoral artery(40%to 50%of the blood volume)to establish a model of hemorrhagic shock after exposure to the plateau environment.The effect of dexmedetomidine on pulmonary vascular permeability was observed by changes in lung water content,pulmonary microvascular permeability and alveolar lavage fluid protein concentration after prophylactic administration of dexmedetomidine;The effect of dexmedetomidine on respiratory function was observed by measuring respiratory rate and tidal volume;Pathological changes of lung tissue was detected by HE staining;Blood gas analysis was used to detect the effect of dexmedetomidine on arterial blood gases and survival rate.ResultsCompared with the sham group,the lung water content,pulmonary microvascular permeability and alveolar lavage fluid protein concentration of the rats in the HS group increased(P<0.05).The respiratory rate increased(P<0.05),and the tidal volume and minute ventilation decreased(P<0.05).Results of HE staining showed that the alveolar wall was thickened,and the lumen of alveoli was partially narrowed,with infiltration of inflammatory cells.Results of arterial blood gas suggested there was acidosis,and rats were in a hypoxic state(P<0.05).Compared with the HS group,the rats in the LR group had aggravated pulmonary oedema.HE staining showed there was a fusion of alveolar sacs,lung tissue structure was destroyed and appeared obvious inflammatory cell infiltration.Respiratory rate and tidal volume increased,and arterial blood gas got deteriorated(P<0.05).Dexmedetomidine significantly improved the lung function of rats with hemorrhagic shock pulmonary oedema after exposure to the plateau environment,and there was a decreased in pulmonary microvascular permeability,lung water content and alveolar lavage fluid protein concentration,compared with the lactated Ringer’s solution resuscitation group(P<0.05).The tidal volume,respiratory rate and minute ventilation of the rats tended to be higher than that of the plateau control group(P<0.05).HE staining results showed that the alveolar structure tended to be intact,and the exudation in the alveolar lumen was reduced or even disappeared.Arterial blood gas analysis suggested that the level of acidosis was improved(P<0.05),which eventually improved the survival rate.ConclusionPulmonary edema is more likely to be induced during the resuscitation of rats with hemorrhagic shock after exposure to the plateau environment,and prophylactic administration of dexmedetomidine(10μg/kg)is effective in preventing the development of pulmonary oedema.