盐酸戊乙奎醚对幼鼠高氧急性肺损伤的影响及其与内质网应激途径细胞凋亡的关系  

Effect of penehyclidine hydrochloride on hyperoxia-induced acute lung injury and the relationship with endoplasmic reticulum stress-dependent apoptosis in infantile rats

作　　者：黄宇[1] 林传涛[1] 王玉苹[1] 缪丽艳[1] 张励[1] 严志荣 高翔[1] Huang Yu;Lin Chuantao;Wang Yuping;Miao Liyan;Zhang Li;Yan Zhirong;Gao Xiang(Department of Anesthesiology,Fujian Provincial Maternal and Children′s Hospital,Fuzhou 350001,China)

机构地区：[1]福建省妇幼保健院麻醉科,福州350001

出　　处：《中华麻醉学杂志》2019年第5期625-628,共4页Chinese Journal of Anesthesiology

基　　金：福建省妇幼保健院院内科研课题资助计划(妇保院研16-28)

摘　　要：目的评价盐酸戊乙奎醚对幼鼠高氧急性肺损伤的影响及其与内质网应激途径细胞凋亡的关系。方法清洁级雄性SD幼鼠96只,体重40~50 g,14日龄,采用随机数字表法分为4组(n=24):对照组(C组)、盐酸戊乙奎醚组(P组)、高氧组(HO组)和高氧+盐酸戊乙奎醚组(HP组)。P组和HP组腹腔注射盐酸戊乙奎醚0.3 mg/kg,于每日同一时间点给药,共计3 d。给药后第4天采用吸氧72 h,氧浓度大于90%的方法制备高氧急性肺损伤模型。吸氧结束时处死幼鼠,取肺组织,测定湿重/干重比值(W/D比值);观察肺组织病理学结果,测定肺泡损伤定量评价指标(IQA)和线粒体损伤评分;采用TUNEL法确定细胞凋亡指数(AI);分别采用Western blot法和RT-PCR法测定葡萄糖调节蛋白78(GRP78)和CCAAT增强子结合蛋白同源蛋白(CHOP)及其mRNA的表达水平。结果与C组比较,HO组和HP组肺组织W/D比值、IQA、AI和线粒体损伤评分升高,GRP78和CHOP及其mRNA表达上调(P<0.05),P组上述指标差异无统计学意义(P>0.05)。与HO组比较,HP组肺组织W/D比值、IQA、AI和线粒体损伤评分降低,GRP78和CHOP及其mRNA表达下调(P<0.05),肺组织病理学损伤减轻。结论盐酸戊乙奎醚可减轻幼鼠高氧急性肺损伤,机制可能与抑制内质网应激途径细胞凋亡有关。Objective To evaluate the effect of penehyclidine hydrochloride on hyperoxia-induced acute lung injury and the relationship with endoplasmic reticulum stress-dependent apoptosis in infantile rats.Methods Ninety-six clean-grade male infantile Sprague-Dawley rats,weighing 40-50 g,aged 14 days,were allocated into 4 groups(n=24 each)using a random number table method:control group(C group),penehyclidine hydrochloride group(P group),hyperoxia group(HO group)and hyperoxia plus penehyclidine hydrochloride group(HP group).Infantile rats were intravenously injected with penehyclidine hydrochloride(0.3 mg/kg)at the same time point every day for 3 consecutive days in P and HP groups.Infantile rats were injected with the equal volume of normal saline instead of penehyclidine hydrochloride in C and H groups.Acute lung injury was induced by inhaling oxygen at concentration greater than 90%for 72 h starting from 4th day after administration.Infantile rats were sacrificed at the end of inhaling,and lungs were removed for examination of the pathological changes and for determination of weight to dry weight ratio(W/D ratio),index of quantitative evaluation for alveolar damage(IQA),pneumonocyte apoptosis(using TUNEL),expression of glucose-regulated protein 78(GRP78)and CCAAT/enhancer-binding protein homologous protein(CHOP)protein and mRNA in lung tissues(by Western blot or using reverse transcription-polymerase chain reaction).The mitochondrial injury score was assessed,and apoptotic index(AI)was determined.Results Compared with C group,the W/D ratio,IQA,AI and mitochondrial injury score were significantly increased,and the expression of GRP78 and CHOP protein and mRNA was up-regulated in HO and HP groups(P<0.05),and no significant change was found in the parameters mentioned above in group P(P>0.05).Compared with HO group,the W/D ratio,IQA,AI and mitochondrial injury score were significantly decreased,the expression of GRP78 and CHOP protein and mRNA was down-regulated(P<0.05),and the pathological changes of lung tissues were sig

关 键 词：胆碱能拮抗剂 急性肺损伤 高氧症 内质网应激 细胞凋亡 

分 类 号：R73[医药卫生—肿瘤]