生长激素释放肽对百草枯中毒小鼠急性肺损伤的保护作用  

Protective effect of ghrelin against paraquat-induced acute lung injury in mice

作　　者：刘瑶[1] 郭瑞娟[1] 王菲[1] 赵光举[1] 卢中秋[1] 邱俏檬[1] 

机构地区：[1]温州医科大学附属第一医院急诊医学中心,325000

出　　处：《中华劳动卫生职业病杂志》2014年第3期190-194,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：浙江省“十二五”重点学科建设计划资助;浙江省医学创新学科（11-CX26）;浙江省中医药重点学科（2012-XK-A28）

摘　　要：【摘要】目的探讨百草枯（paraquat，PQ）中毒的小鼠肺组织中血红素加氧酶1（heineoxygenase1，HO-1）、醌氧化还原酶1（NAD（P）H：quinineoxidoreductase1，NQ01）和核因子E2相关因子2转录因子（nuclearfactorerythroid2-relatedfactor2，Nrf2）的变化及生长激素释放肽（ghrelin）对PQ中毒小鼠急性肺损伤的保护效应。方法50只清洁级ICR小鼠按随机数字表法分为正常对照组（10只）、PQ染毒组（10只）、16．58、33．15、49．73μg／kg生长激素释放肽干预组（30只），PQ（20mg／kg）染毒方式及生长激素释放肽干预均通过腹腔内注射实现；取各组小鼠肺组织，HE染色，光学显微镜下观察小鼠肺组织病理学变化，蛋白免疫印迹法westernblot）检测核内Nrf2蛋白水平的改变，双抗夹心酶联免疫吸附法（ELISA）法测定肺组织HO．1、NQ01活力变化，化学比色法检测丙二醛（malondiadehyde，MDA）蛋白含量、髓过氧化物酶（myeloperoxidase，MPO）活力。另将40只小鼠分为PQ染毒组（10只）、16．58、33．15、49．73μg／kg干预组（各10只），处理同上，记录72h内各小鼠死亡时间和临床表现。结果与正常对照组比较，PQ染毒组核内Nrf2蛋白增加，HO-1、NQ01及MPO活力明显升高，MDA含量升高，差异均有统计学意义（P〈0．05）。与P0染毒组比较，干预组核内Nrf2蛋白明显增高，HO-1、NQ01活力明显升高，MDA含量和MPO活力降低，差异均有统计学意义（P〈0．01）。PQ组在染毒后肺组织损害明显，干预组肺损害较之有所减轻。干预组小鼠死亡率明显低于PQ染毒组，其中高剂量干预组与PQ染毒组的差异有统计学意义（P〈0．05）。结论生长激素释放肽能上调PQ染毒小鼠核内Nrf2的蛋白表达，增加140-1、NQ01活力，降低MPO活力，减少MDA含量，对PQ中毒小鼠急性肺损伤有保护作用。Objective To measure the levels of ghrelin：i＇nduced expression or activation of nuclear factor erythroid 2-related factor 2 （Nrf2）, heme oxygenase-1 （HO-1）, and NAD（P）H： quinone oxidoreductase 1 （NQO1） in the PQ-injured lungs of mice and to evaluate the protective effect of ghrelin against paraquat （PQ）- induced acute lung injury in mice. Methods According to the random number table method, 50 ICR mice of clean grade were assigned to 5 groups： normal control group （n=10）, PQ group （n=10）, and ghrelin intervention groups （n=30）. For PQ group, mice were injected with a single dose of PQ （20 mg/kg, i＇.p.）; for ghrelin intervention groups, mice were injected with a single dose of PQ （20 mg/kg, i.p.）, and then ghrelin was injected at three concentrations （16.58, 33.15, and 49.73 txg/kg）. Lung tissues were collected and proceeded to the following studies. HE staining was used for histopathological examination under a light microscope, and the changes in nuclear expression of Nrf2 were evaluated by Western blot. The activities of HO-I and NQO1 were measured by ELISA. Malondialdehyde （MDA） content and MPO activity were measured by colorimetry. Another 40 mice were divided into PQ group （n=10） and 16.58, 33.15, and 49.73 Ixg/kg ghrelin intervention groups （n= 10 for each）; mortality and clinical manifestations were recorded within 72 h. Results Compared with the normal control group, the PQ group showed significant increases in nuclear protein level of Nrf2, content of MDA, and activities of HO-1, NQO1, and MPO （P〈0.05 for all）. Compared with the PQ group, ghrelin treatment significantly increased the expression of Nrf2 and activities of HO-1 and NQO1 and significantly reduced the content of MDA and activity of MPO （P〈0.01 for all）. Histopathological studies indicated that ghrelin showed an antioxidant property that reduced the histological changes induced by PQ in the lungs. The ghrelin intervention groups had a significantly lower mortality t

关 键 词：GHRELIN 百草枯 肺损伤 氧化应激 

分 类 号：R595.4[医药卫生—内科学]