右美托咪啶对急性肺损伤大鼠肺功能的保护作用及机制

Protective Effect of Dexmedetomidine on Lung Function in Rats with Acute Lung Injury and Its Mechanism

【目的】研究右美托咪啶（DEx）对急性肺损伤（Au）的保护作用及机制。[方法]12周龄健康SPF级SD大鼠45只，随机分为对照组（NS组），ALl组和DEX组，每组15只。ALI组腹腔注射脂多糖（LPS）500〉g／kg；DEX组先予DEX100μg／kg腹腔注射，30min后腹腔注射LPS500μg／kg；NS组腹腔注射相同容积的生理盐水。分别在模型构建后2h、6h、12h、24h采集颈动脉血液进行血气分析和计算氧合指数（Pa02／FiOz），并采集支气管肺泡灌洗液（BALF）检测中性粒细胞凋亡情况，分别检测2h和12h的BALF中IL-18、TNF-a水平。【结果】ALI组Pa02／FiO。逐渐下降，在24h内，ALI组共有7只大鼠死亡，病死率为46．7％。在6～24h的3个时间点中，DEX组PaO2／FiO2逐渐上升，与Au组相比有显著差异（P〈0．05或P〈0．01）；DEX组病死率为20％。在6～24h的时间段内，ALI组的多性核中性粒细胞（PMN）凋亡比率开始明显下降，与Ns组相比具有明显差异（P〈0．05）。DEX组PMN凋亡比率呈缓慢下降趋势，在12h时和24h时，DEX组PMN凋亡率显著高于ALI组（P〈0．05）。在12h时，与Ns组相比，ALI组白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平显著升高（P〈0．05），DEX组差异不显著（P〉0．05）；而DEX组与ALI组相比，IL-1β、TNF-α水平均明显下降（P〈0．05）。【结论】DEX可改善ALI大鼠的肺功能，促进肺组织局部PMN凋亡过程和减轻炎症反应。

[Objective] To explore the protective effect of dexmedetomidine（DEX） on acute lung injury （ALI） and its mechanism. [Methods] Totally 45 12-week-old healthy SPF-grade Sprague Dawley rats were randomly divided into control group（NS group） and acute lung injury group（ALI group） and dexmedetomidine group（DEX group） with 15 in each group. ALI group received the intraperitoneal injection of lipopolysaccha- ride（LPS） 500μ g/kg. DEX group first received intraperitoneal injection of DEX 100μg/kg, and 30rain later intraperitoneal injection of LPS 500μg/kg. NS group received intraperitoneal injection of the same volume of normal saline. Carotid artery blood 2h, 6h, 12h and 24h after model establishment was collected for blood gas analysis. Oxygenation index（PaO2/FiO2 ） was calculated. Bronchoalveolar lavage fluid（BALF） was collected to detect the apoptosis of polymorphonuclear neutronphil（PMN）. IL-113 and TNF-a levels in BALF were detec- ted at 2h and 12h. [Results] In ALI group, PaO2/FiO2 gradually declined and 7 rats died within 24h, and the fatality rate was 46.7%. At 3 time points in 6-24h, PaO2/FiO2 in DEX group gradually rose, and there was significant difference between DEX group and ALI group（ P （0.05 or P （0.01）. The fatality rate of DEX group was 20%. At 6h-24 h, PMN apoptosis ratio of ALI group began to decrease obviously, and there wag significant difference between ALI group and DEX group（ P ~0.05）. In DEX group, PMN apoptosis rate slowly declined. PMN apoptosis rate in DEX group was markedly higher than that in ALI group（ P〈0.05）. Compared with NS group, IL-113 and TNF-a levels in ALI group at 12h markedly increased（ P 〈0.05）, but there was no significant difference in DEX group（ P 〉0.05）. Compared with ALI group, IL-I 13 and TNF-a levels in DEX group obviously decreased（ P （0.05）. [Conclusion] DEX can improve pulmonary function of ALI rats, promote local neutrophil apoptosis process in lung tissue and reduce inflammation reaction.