p38MAPK—HSP27通路在右美托咪定减轻小鼠内毒素性急性肺损伤中的作用  

Role of p38MAPK-HSP27 signaling pathway in attenuation of LPS-induced acute lung injury by dexmedetomidine in mice

作　　者：徐颖臻 张秀丽[2] 张如意[1] 宁巧庆 尹雪[2] 李春丽[2] 赵文香[1] 

机构地区：[1]滨州医学院附属医院麻醉科,256603 [2]滨州医学院药学院

出　　处：《中华麻醉学杂志》2015年第3期366-369,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价p38丝裂原激活的蛋白激酶（p38MAPK）-热休克蛋白27（HSP27）（p38MAPK—HSP27）通路在右美托咪定减轻小鼠内毒素性急性肺损伤中的作用。方法健康昆明种雄性小鼠40只，体重20～25g，2月龄，采用随机数字表法，将其分为4组：正常对照组（C组）、脂多糖（LPS）组、低剂量右美托咪定＋LPS组（D，组）和高剂量右美托咪定＋LPS组（D2组）。D1组和D2组分别腹腔注射右美托咪定25、50μg／kg，1h后腹腔注射LPS5mg／kg。注射LPS后6h，进行左肺支气管肺泡灌洗，收集支气管肺泡灌洗液（BALF），测定蛋白、肿瘤坏死因子-α（TNF—d）和白细胞介素-1β（IL-1β）的浓度；取右肺，光镜下观察病理学结果，计算肺组织湿重／干重（W／D）比值，检测肺组织磷酸化p38MAPK（p-p38MAPK）、p38MAPK、磷酸化丝裂原激活蛋白激酶激活的蛋白激酶-2（p-MAP—KAPK-2）、MAPKAPK-2、磷酸化HSP27（p-HSP27）和HSP27表达，并计算p-p38MAPK与p38MAPK表达的比值（p-p38MAPK，p38MAPK）、P—MAPKAPK一2与MAPKAPK一2表达的比值（p-MAPKAPK-2／MAPKAPK-2）和P—HSP27与HSP27表达的比值（P—HSP27／HSP27）。结果与C组比较，LPS组肺W／D比值、BALF中蛋白、TNF—OL和IL一1B的浓度升高，肺组织p—p38MAPK／p38MAPK、p-MAPKAPK-2／MAPKAPK-2及p-HSP27／HSP27升高（P〈0．05）；与LPS组比较，D1组和D2组肺W／D比值、BALF中蛋白、TNF-α和IL-1β的浓度降低，肺组织p—p38MAPK／p38MAPK、p-MAPKAPK-2／MAPKAPK-2及P—HSP27／HSP27降低（P〈0．05）；D1组和D2组肺组织病理学损伤明显轻于LPS组。结论右美托咪定可能通过抑制p38MAPK—HSP27通路减轻小鼠内毒素性急性肺损伤。Objective To evaluate the role of p38 mitogen-activated protein kinase （p38MAPK）- heat shock protein 27 （HSP27） signaling pathway in attenuation of lipopolysaecharide （LPS）-induced acute lung injury （ALI） by dexmedetomidine in mice. Methods Forty male Kunming mice, aged 2 months, weighing 20-25 g, were equally and randomly divided into 4 groups using a random number table： control group （group C）, LPS group, low-dose dexmedetomidine ＋ LPS group （group D1 ）, and high-dose dexmedetomidine ＋ LPS group （ group D2） . Dexmedetomidine 25 and 50 Ixg/kg were injected intraperitone- ally in Dtand D2 groups, respectively, and 1 h later LPS 5 mg/kg was injected intraperitoneally. At 6 h af- ter LPS injection, the left lung was lavaged, and broncho-alveolar lavage fluid （BALF） was collected for determination of concentrations of protein, tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. The right lung was removed for examination of the pathological changes （under the light microscope） and for detection of expression of phosphorylation of p38MAPK （p-p38MAPK）, p38MAPK, phosphorylation of MAPK-activated protein kinase 2 （p-MAPKAPK-2）, MAPKAPK-2, phosphorylation of HSP27 （p- HSP27） and HSP27 in lung tissues. The wet to dry lung weight （W/D） ratio was calculated. The ratios of p-p38MAPK/p38MAPK, p-MAPKAPK-2/MAPKAPK-2 and p-HSP27/HSP27 were calculated. Results Compared with group C, the W/D ratio, concentrations of protein, TNF-ot and IL-l[3 in the BALF, and ratios of p-p38MAPK/p38MAPK, p-MAPKAPK-2/MAPKAPK-2 and p-HSP27/HSP27 were significantly increased in group LPS. Compared with group LPS, the W/D ratio, concentrations of protein, TNF-α and IL-lβ in the BALF, and ratios of p-p38MAPK/p38MAPK, p-MAPKAPK-2/MAPKAPK-2 and p-HSP27/ HSP27 were significantly decreased in D1 and Dzgroups. The pathological changes of the lung were signifi- cantly reduced in D~ and D2 groups as compared to LPS group. Conclusion Dexmedetomidine attenuates LPS-indueed ALl in mi

关 键 词：P38丝裂原活化蛋白激酶类 热休克蛋白质类 右美托咪啶 呼吸窘迫综合征 成人 内毒素血症 

分 类 号：R614[医药卫生—麻醉学]