右美托咪定通过抑制JAK2/STAT3通路改善脂多糖诱导的小鼠急性肺损伤  

Dexmedetomidine attenuates acute lung injury induced by lipopolysaccharide in mouse through inhibiting of the JAK2/STAT3 signal pathway

作　　者：徐颖臻 王耀岐[1] 宁巧庆 张如意[1] 岳桂芳[1] 赵文香[1] 

机构地区：[1]滨州医学院附属医院麻醉科,滨州市256603

出　　处：《临床麻醉学杂志》2015年第11期1105-1108,共4页Journal of Clinical Anesthesiology

摘　　要：目的研究右美托咪定对脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠JAK2/STAT3通路的作用。方法雄性昆明小鼠36只,随机均分为三组:正常组(C组)、模型组(L组)和右美托咪定预处理组(D组)。取小鼠右肺下叶,称量并计算湿/干比重(W/D),对右肺上叶进行苏木素-伊红(HE)染色观察小鼠肺组织病理学改变,BCA法检测支气管肺泡灌洗液(BALF)中蛋白含量,用ELISA试剂盒检测BALF上清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)及髓过氧化物酶(MPO)水平;qRT-PCR定量分析肺组织中TNF-α、IL-6mRNA水平;Western blot方法检测肺组织中p-JAK2、JAK2、p-STAT3、STAT3蛋白的含量。结果与L组比较,C组、D组肺损伤评分明显降低、小鼠肺W/D、BALF中蛋白含量明显减少,BALF中TNF-α、IL-6及MPO浓度明显降低,肺组织TNF-α和IL-6mRNA表达明显减少,p-JAK2/JAK2和p-STAT3/STAT3相对量明显减少(P<0.05)。结论右美托咪定可能通过抑制JAK2/STAT3通路减轻LPS诱导的小鼠ALI。Objective To explore the effects of dexmedetomidine （Dex） on the janus-activated kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway in lipopolysac- charide （LPS）-induced acute lung injury （ALl） in mouse. Methods Thirty-six Kunming mice, were randomly divided into three groups of 12 mice each： Control group （group C）, LPS group （group L） and Dex＋LPS group （group D）. Mice were challenged with LPS （5 mg/kg） in 100μl saline via intra- peritoneal administration with or without intraperitoneal injection of Dex 25μg/kg 1 h before LPS ad- ministration. Mice in group C received 100-/11 saline. Lung tissues were harvested 6 h after lipopo- lysaccharide challenge, and the wet/dry lung ratio （W/D） was calculated. Lungs were used for histo- logic evaluation by hematoxylin and eosin staining and the lung injury was graded using a modified ALI score. The BCA method was used to measure the protein concentration in the BALF, and the levels of mouse tumor necrosis factor-α （TNF-α）, interleukin （IL）-6 and myeloperoxidase （MPO） were measured using enzyme-linked immunosorbent assay kits. TNF-α and IL-6 mRNA expression were determined using quantitative real-time PCR. We employed Western blotting to observe changes of p-JAK2, JAK2, p-STAT3 and STAT3 in the lungs. Results Compared with group L, lung injury score decreased significantly, W/D of lung, BALF protein content decreased significantly, TNF-α, IL-6 and MPO concentrations in BALF were decreased significantly , The expression of TNF-α and IL- 6 mRNA in lung tissue was decreased significantly, p-JAK2/JAK 2 and p-STAT3/STAT3 p-content were increased significantly in groups C and D （P〈0. 05）. Conclusion Dex may inhibit the JAK2/ STAT3 pathway reduse ALI induced by LPS in mouse.

关 键 词：急性肺损伤 脂多糖 右美托咪定 JANUS激酶 信号转导转录激活因子 

分 类 号：R614[医药卫生—麻醉学]