盐酸戊乙奎醚预先给药对脓毒症小鼠急性肺损伤时肺组织β-arrestin-2表达的影响  

Effects of penehyclidine hydrochloric pretreatment on expression of β-arrestin-2 in the lung tissue in sepsisinduced acute lung injury in mice

作　　者：李进杰[1] 肖飞[2] 詹佳[3] 张宗泽[3] 陈凯[3] 王焱林[3] 韩毅[3] 

机构地区：[1]430079武汉大学口腔医院麻醉科 [2]华中科技大学附属普爱医院骨科 [3]武汉大学中南医院麻醉科

出　　处：《中华麻醉学杂志》2012年第5期593-596,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81101408）;武汉大学自主科研创新项目（111169）

摘　　要：目的探讨盐酸戊乙奎醚预先给药对脓毒症小鼠急性肺损伤时肺组织3-抑制蛋白-2（β-arrestin-2）表达的影响。方法健康雌性昆明小鼠30只，6周龄，体重18～20g，采用随机数字表法，将其随机分为3组（n=10）：假手术组（S组）、脓毒症组（CLP组）和盐酸戊乙奎醚预先给药组（PHC组）。CLP组和PHC组采用盲肠结扎并穿孔法制备脓毒症模型。PHC组于模型制备前1h时腹腔注射盐酸戊乙奎醚0．45mg／kg，S组和CLP组于模型制备前1h时腹腔注射等容量生理盐水。模型制备后12h时，采血和收集肺泡灌洗液测定肺通透性指数，采用化学比色法测定肺组织MPO活性，采用ELISA法测定肺组织IL-6含量，采用Westernblot法测定肺组织β—arrestin-2蛋白表达，采用RT-PCR法测定肺组织β-arrestin-2mRNA表达。结果与S组比较，CLP组肺通透性指数、肺组织MPO活性和IL-6含量均升高，肺组织β—arrestin-2蛋白表达下调，β—arrestin-2mRNA表达上调（P〈0．05），PHC组肺通透性指数、肺组织MPO活性和IL。6含量均升高，肺组织β—arrestin-2蛋白表达上调，β—arrestin-2mRNA表达下调（P〈0．05）。与CLP组比较，PHC组肺通透性指数、肺组织MPO活性和IL-6含量均降低，肺组织β—arrestin-2蛋白表达上调，p—arrestin-2mRNA表达下调（P〈0．05）。结论盐酸戊乙奎醚预先给药减轻脓毒症小鼠急性肺损伤的机制可能与上调肺组织β—arrestin-2的蛋白表达有关。Objective To investigate the effects of penehyclidine hydrochloric （PHC） pretreatment on the expression of β-arrestin-2 in the lung tissue in sepsis-induced acute lung injury in mice. Methods Thirty female Kunming mice, aged 6 weeks, weighing 18-20 g, were randomly divided into 3 groups（ n = 10 each） ： sham operation group （group S）; sepsis group （group CLP） and penehyclidine hydrochloric pretreatment group （group PHC）. Sepsis was induced by cecal ligation and puncture （CLP） in groups CLP and PHC. Penehyclidine hydro- chloric 0.45 mg/kg was injected intraperitoneally at 1 h before CLP in group PHC. While the equal volume of normal saline was given instead of penehyclidine hydrochloric in groups S and CLP. At 12 h of CLP, the animals were sacrificed, and the lung tissues were removed for determination of MPO activity （by colorimetry）, IL-6 content （by ELISA）, β-arrestin-2 mRNA and protein expression （by RT-PCR and Western blot respectively）. Blood samples and bronchoalveolar lavage fluid were collected to calculate pulmonary vascular permeability index （PVPI）. Results Compared with group S, PVPI, IL-6 content and MPO activity were significantly increased, the expression of ~3-arrestin-2 protein was significantly down-regulated while the expression of β-arrestin-2 mRNA was up-regulated in group CLP, and PVPI, IL-6 content and MPO activity were significantly increased, the expression of β-arrestin-2 protein was significantly up-regulated, while the expression of β-arrestin-2 mRNA was down-regulated in group PHC（ P 〈 0.05）. Compared with group CLP, PVPI, IL-6 content, and MPO activity were significantly decreased, the expression of β-arrestin-2 protein was significantly up-regulated, while the expression of β-arrestin-2 mRNA was down-regulated in group PHC （P 〈 0.05）. Conclusion PHC pretreatment can attenuate the lung injury induced by sepsis in mice through up-regulating the expression of β-arrestin-2 protein.

关 键 词：胆碱能拮抗剂 抑制蛋白 肺 脓毒症 呼吸窘迫综合征 成人 

分 类 号：R459.7[医药卫生—急诊医学]