Nod样受体蛋白3炎性体抑制剂格列苯脲对机械通气致小鼠急性肺损伤的保护作用

Protective effects of Nod-like receptor protein-3 inflammasome inhibitor glyburide for mouse acute lung injury induced by mechanical ventilation

目的 探究Nod样受体蛋白3（Nod-like receptor protein-3,NLRP3）炎性体抑制剂格列苯脲对机械通气导致的小鼠急性肺损伤是否具有保护作用. 方法 28只7～9周的清洁级ICR雄性小鼠,按完全随机分组法分为4组：对照组（CON组,6只）、格列苯脲组（GLY组,6只）、机械通气组（VEN组,8只）和格列苯脲＋机械通气组（GLY＋VEN组,8只）.VEN组和GLY＋VEN组机械通气4h后与CON组及GLY组麻醉插管后4h测定肺泡灌洗液中蛋白含量及炎性细胞数量,测量肺组织湿/干重比（wet/dry,W/D）,观察肺组织病理学改变,ELISA法检测肺组织IL-1β、IL-6、TNF-α的含量. 结果 VEN组肺泡灌洗液中蛋白浓度和细胞数量[（0.534±0.104） g/L和（3.4±0.7）×105/ml]比CON组[（0.167±0.021） g/L和（1.9±0.5） ×105/ml]升高（P＜0.01）;GLY＋VEN组肺泡灌洗液中蛋白浓度和细胞数量[（0.425±0.083） g/L和（2.4±0.6） ×105/ml]比VEN组下降（P＜0.05）.VEN组肺组织W/D（5.1±0.5）与CON组（4.4±0.4）比较,差异有统计学意义（P＜0.01）,GLY ＋VEN组肺组织W/D（4.7±0.4）与VEN组比较,差异有统计学意义（P＜0.05）.VEN组和GLY＋VEN组肺组织中IL-1β、IL-6和TNF-α蛋白表达与CON组比较,明显升高（P＜0.05）,GLY＋VEN组IL-1β和IL-6表达与VEN组比较,表达明显降低（P＜0.05）.结论 机械通气前给予格列苯脲可有效减少小鼠肺组织炎症细胞聚集,减轻肺水肿,机制可能与其抑制炎性体的激活有关.

Objective To investigate whether Nod-like receptor protein-3 （NLRP3） inflammasome inhibitor glyburide exerts protective effects for mouse acute lung injury induced by mechanical ventilation.Methods Twenty-eight male ICR mice were randomly divided into 4 groups：control group （group CON,n=6）,glyburide group （group GLY,n=6）,mechanical ventilation group （group VEN,n=8）,and glyburide＋mechanical ventilation group （group GLY＋VEN,n=8）.The content of protein and inflammatory cell counts in bronchoalveolar lavage fluid were measured after 4 h ventilation,the wet/dry（W/D） and morphopathogical changes of lung tissue were examined.Lung tissues were homogenated to detect the IL-1β,IL-6 and TNF-α levels by ELISA.Results The concentration of protein and cell counts in group VEN [（0.534±±0.104） g/L and （3.4±0.7） ×105/ml] were higher than group CON [（0.167±0.021） g/L and （1.86±0.46） ×105/ml]（P〈0.01）,and those in group GLY＋VEN[（0.425±0.083） g/L and （2.4±±0.6） ×105/ml] were lower than group VEN （P〈0.05）.W/D was higher in group VEN（5.1±0.5） than group CON（4.4±0.4）（P〈0.01） and group GLY＋VEN（4.7±0.4）（P〈0.05）.The IL-1β,IL-6 and TNF-α levels in lung tissue were increased in group VEN and group GLY＋VEN （P〈0.05）.The IL-1β and IL-6 levels had significant statistical differences between group GLY＋VEN and group VEN （P〈0.05）.Conclusions Our results indicate that pre-treated with glyburide could significantly attenuate mechanical ventilation-induced recruitment of inflammatory cells and lung edema,which might be attributed to the deactivation of NLRP3 inflammasome.