右美托咪定对慢性阻塞性肺疾病大鼠机械通气时肺脏氧化应激反应和炎性因子的影响

Effect of Dexmedetomidine on Oxidative Stress and Inflammatory Factors of the Lung During Mechanical Ventilation in Rats with Chronic Obstructive Pulmonary Disease

目的探讨右美托咪定对慢性阻塞性肺疾病(COPD)大鼠机械通气时肺脏氧化应激反应和炎性反应的影响。方法选取周龄为6~8周的清洁级SD大鼠24只,按随机抽签法均分为对照组、试验组及模型组,各8只。对照组不予任何干预,试验组和模型组大鼠置自制烟室内,建立COPD模型。试验组通过静脉给药右美托咪定10μg/kg,对照组与模型组均予等量生理盐水。分别于注射药物6h后测定大鼠的肺功能指标水平,以酶联免疫吸附法检测血清白细胞介素6(IL-6)、IL-1β、肿瘤坏死因子-α(TNF-α)、脑皮质丙二醛(MDA)和超氧化物歧化酶(SOD)水平,随后处死大鼠,测定其肺脏干湿重比。结果3组大鼠呼气峰流速(PEF)、第1秒用力呼气容积(FEV1)、FEV占用力肺活量比值(FEV1/FVC)水平逐渐降低,血清IL-6,IL-1β,TNF-α水平逐渐升高,肺脏干湿重比水平逐渐升高,MDA水平逐渐升高、SOD水平逐渐降低,且单因素分析显示组间差异均显著(P<0.05)。结论右美托咪定可显著减轻COPD大鼠机械通气时肺脏氧化应激反应和炎性反应,有利于减轻大鼠肺损伤。

Objective To investigate the effect of dexmedetomidine on oxidative stress and inflammatory response of the lung during mechanical ventilation in rats with chronic obstructive pulmonary disease( COPD). Methods Totally 24 clean SD rats aged 6 to 8 weeks were randomly divided into the control group,experimental group and model group,8 rats in each group. The rats in the control group were not given any intervention,while the rats in the experimental group and model group were placed in self-made smoke chamber to establish COPD model. 10 μg/kg of Dexmedetomidine was administered intravenously to the rats in the experimental group,while the same amount of normal saline was given to the rats in the control group and the model group. 6 h after the injection of drugs,the lung function indexes of the rats were measured. The levels of interleukin-6( IL-6),IL-1β,tumor necrosis factor-α( TNF-α) in serum,the levels of malondialdehyde( MDA) and superoxide dismutase( SOD) in the cerebral cortex were measured by enzyme-linked immunosorbent assay. Then the lung dry-wet weight ratio of the rats in three groups was determined after rats were sacrificed. Results The levels of peak expiratory velocity( PEF),1 s forced expiratory volume( FEV1),FEV/forced vital capacity( FEV1/FVC) showed a gradually decreasing trend,the levels of serum IL-6,IL-1β and TNF-α showed a gradually increasing trend,the lung dry-wet weight ratio of the rats showed a gradually increasing trend,the level of MDA showed a gradually increasing trend,while the level of SOD showed a gradually decreasing trend in the three groups,and the univariate analysis showed that there was significant difference in these indicators among the three groups( P < 0. 05). Conclusion Dexmedetomidine can significantly reduce the oxidative stress and inflammatory response of the lung in rats with COPD during mechanical ventilation,which is beneficial to alleviate lung injury in rats.