右美托咪定对内毒素诱导的急性肺损伤大鼠p38丝裂原激活的蛋白激酶的活化及炎症反应的影响  

Dexmedetomidine makes the anti-inflammation effect by blocking p38 mitogen-activated protein kinase in thelipopolysaccharides -induced acute lung injury in rats

作　　者：杨颖[1] 王鹏[1] 封光[2] 刘功俭[2] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室&江苏省麻醉与镇痛应用技术重点实验室,221004 [2]徐州医学院附属医院麻醉科

出　　处：《国际麻醉学与复苏杂志》2014年第3期203-206,共4页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金项目（81200056）;江苏省高校自然科学研究项目（11KJD320003）

摘　　要：目的探讨右美托咪定（dexmedetomidine，Dex）对内毒素（1ipopolysaccharides，LPS）诱导的急性肺损伤（acutelunginjury，Au）大鼠肺部P38丝裂原活化蛋白激酶（p38mitogen-activatedproteinkinase，p38MAPK）和炎症反应的影响。方法健康成年雄性SD大鼠采用完全随机分组法分为5组，每组10只：生理盐水组（C组），LPS组，0．2μg·kg^-1·h^-1Dex处理组（Dex0．2组），1μg·kg^-1·h^-1Dex处理组（Dexl组），5μg·kg^-1·h^-1Dex处理组（Dex5组）。各Dex处理组在给予LPS（腹腔注射LPS8ms／kg）诱导ALI之前输注Dex负荷剂量1μg·kg^-1·h^-1 10min，然后持续按各处理组相应剂量输注Dex至各时间点。C组与LPS组输注等体积的生理盐水（1ml·kg^-1·h^-1）至各时间点。收集肺泡灌洗液（bronchoalveolarlavagefluid，BALF），动脉血和肺组织标本，进行动脉血气分析，测量肺组织湿，干重比，观察肺病理学改变，检测支气管BALF中肿瘤坏死因子-a（turnoutnecrosisfactor-a，TNF啾）和白介素（interleukin，IL）．10的浓度，利用Westernblot检测各组大鼠肺组织中p38MAPK和磷酸化水平。结果在注射了LPS后，各组大鼠的动脉氧分压均明显降低（61．3±1．2）VS（131．7±4．7）（P〈0．05）；C组大鼠肺部未见明显的病理改变，LPS组、Dex0．2组和Dexl组大鼠肺部有明显的病理改变，而Dex5组大鼠肺部病理改变较LPS组明显减轻；肺组织湿／干重比LPS组明显的高于C组（5．4±0．3）VS（3．6±0.3）（P〈0．05），Dex5组明显低于LPS组（4．4±0．4）VS（5．4±0．3）（P〈0．05）；磷酸化的p38MAPK、支气管BALF中TNF-α和IL-10水平，LPS组、DexO．2组和Dexl组明显高于c组（P〈0．05），Dex5组明显低于LPS组（P〈0．05）。结论Dex能够减轻LPS造成的大鼠ALI，其机制可能部分与阻断P38MAPK的活化及肺部炎症有关。Objective The aim of this study was to determine whether dexmedetomidine （Dex） could diminish lipopolysaccharide（LPS）-induced pulmonary injury by blocking lung p38 mitogen-activated protein kinase（p38MAPK） activation and inflammation in rats. Methods A total of 50 adult male SD rats were assigned to one of five groups： 0.9% sodium chloride group （C group）, LPS group （LPS group） and LPS plus Dex groups （0.2, 1,5μg/kg per hour） （Dex0.2 group, Dexl group and Dex5 group）. The rats in the LPS plus Dex groups were injected a loading dose of Dex （ 1 μg/kg per hour, intravenous infusion over 10 minutes） followed by LPS administration and Dex infusion at different doses （0.2,1,5 μg/kg per hour, respectively） until the end of experiment. Simultaneously, the LPS and control groups received an equal volume of 0.9% sodium chloride（1 ml/kg per hour） till the end of experiment. Western blot was used to detect the expression of phosphorylation of p38MAPK in lung tissues. Additionally, we examined the concentration of tumour necrosis factor-α（TNF-α） and interleukin（IL）-10 in bronchoalveolar lavage fluid（BALF）, the histopathologic changes of lung, arterial blood gases and lung water content. Results With the administration of LPS, arterial oxygen partial pressure was significantly decreased （61.3±1.2） vs （131.7±4.7） （P〈0.05）, Pathological examination showed that the normal structure of lung was destroyed badly after LPS injection, including intra-alveolar hemorrhage, interstitial edema, alveolar collapse and massive inflammatory ceils infiltration,The lung water content was significantly increased （5.4±0.3） vs （3.6±0.2）（P〈 0.05）. Compared with the LPS group, lung water content of Dex5 group was significantly decreased（4.4±0.4） vs （5.4±0.3）（P〈0.05）.With the administration of LPS, the phospho-p38 MAPK substantially increased immediately, and the concentrations of cytokines were also increased. However, Dex at the dose of 5.0 μ

关 键 词：右美托咪定 抗炎 p38丝裂原激活的蛋白激酶 内毒素 急性肺损伤 

分 类 号：R614[医药卫生—麻醉学]