文献类型：期刊文献

中文题名：杭州市中心城区大气PM2.5暴露致大鼠肺部损伤作用研究

英文题名：Effect of particulate matter 2.5 at urban centre of Hangzhou on lung impairment in rats

作者：田程远[1];严明[1];张云[2];刘珂舟[1];郭淼[1];孙永红[3];薛凌云[1];祝磊[1];徐莹[1]

机构：[1]杭州电子科技大学生命信息与仪器工程学院;[2]绍兴文理学院医学院基础医学部;[3]浙江大学生物医学工程与仪器科学学院浙江省心脑血管检测技术与药效评价重点实验室

年份：2018

卷号：34

期号：4

起止页码：299

中文期刊名：中国应用生理学杂志

外文期刊名：Chinese Journal of Applied Physiology

收录：CSTPCD、、北大核心2017、Scopus、CSCD2017_2018、北大核心、CSCD、PubMed

基金：国家自然科学基金(81700936;61871165);国家自然科学基金联合基金项目(U1609218);浙江省自然科学基金(LY15H180012;LY17H060007);浙江省科技厅公益项目(2016C33078)

语种：中文

中文关键词：大气细颗粒物(PM2.5);大鼠;肺损伤;炎症反应;氧化应激;内质网应激

外文关键词：ambient particle matter 2.5;rat;lung injury;inflammatory response;oxidative stress;ER stress.

中文摘要：目的:探讨杭州市中心城区大气细颗粒物(PM2.5)对大鼠肺部的损伤及其对内质网应激通路的激活作用。方法:在杭州中心城区采用大容积空气颗粒物采样器将PM2.5颗粒采集于石英纤维滤膜上,将收集的PM2.5洗脱于超纯水中,再经真空冰冻干燥处理。将24只雄性SD大鼠随机分为3组:空白对照组,PM2.5低剂量组(5mg/kg BW)和高剂量组(25 mg/kg BW)。采用气管滴注法进行染毒,每周1次,连续染毒4周。末次染毒24 h后麻醉动物,取左肺行HE染色,观察肺组织病理学改变。以化学比色法检测右肺肺泡灌洗液(BALF)中总抗氧化能力(T-AOC)含量、超氧化物歧化酶(SOD)活性和乳酸脱氢酶(LDH)活性,ELISA法测定BALF中肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6 (interleukin-6,IL-6)水平。Western blot法检测肺组织中内质网应激标志物葡萄糖调节蛋白78 (GRP78)表达、磷酸化蛋白激酶受体样内质网激酶(PERK),磷酸化真核细胞翻译起始因子2α(e IF2α),C/EBP同源蛋白(CHOP),肌醇依赖酶1α(IRE1α),X盒结合蛋白1 (XBP1)蛋白的水平。结果:与空白对照组相比,低剂量和高剂量PM2.5染毒均能导致大鼠肺部出现明显的肺泡壁增厚、肺泡腔缩小、间质增生和炎细胞浸润,且随着染毒剂量增加组织损伤加重。PM2.5染毒组大鼠BALF中T-AOC含量和SOD活性呈剂量依赖性下降(P<0.05);而BALF中的LDH活性则呈剂量依赖性上升(P<0.05)。PM2.5染毒导致大鼠肺部促炎因子TNF-α、IL-1β和IL-6的释放呈剂量依赖性增加(P <0. 05)。高剂量PM2. 5染毒组大鼠肺组织中GRP78、磷酸化PERK (p-PERK)、磷酸化e IF2α(p-eIF2α)、CHOP、IRE1α和剪切型X盒结合蛋白1(XBP1-S)表达显著升高,而未剪切型XBP1 (XBP1-U)表达明显下降。结论:杭州市中心城区PM2.5染毒可引起大鼠肺部的炎性损伤,上述损伤可能与肺部氧化应激和内质网应激通路的激活相关。

外文摘要：Objective： To explore the effect of ambient particle matter 2.5（ PM2.5） collected in the urban center of Hangzhou on the lung injury of rats and on the activating of endoplasmic reticulum pathway. Methods： PM2.5 samples were collected on quartz fiber filters using a PM2.5 high-volume air sampler in the urban area of Hangzhou. The collected PM2.5 particles were extracted in ultrapure water and concentrated by vacuum freeze-drying. Twenty-four male Sprague-Dawly（ SD） rats were randomly divided into 3 groups： saline control group,low dose PM2.5 exposure group（ 5 mg/kg BW） and high dose PM2.5 exposure groups（ 25 mg/kg BW）. Each group received intratracheal instillation of PM2.5,once a week for 4 weeks. Twenty-four hours after the last exposure,the rats were narcotized and sacrificed,left lung was isolated and fixed with 4% paraformaldehyde for histopathological detection. The bronchoalveolar lavage fluid（ BALF） was collected from the right lung. The total antioxidant capacity（ T-AOC） level,the activities of superoxide dismutase（ SOD） and lactic dehydrogenase（ LDH） in BALF were detected by chemical colorimetry. The level of tumor necrosis factoralpha（ TNF-α）,interleukin-1 beta（ IL-1β） and interleukin-6（ IL-6） cytokines in BALF was measured by enzyme linked immunosorbent assay（ ELISA）. And the protein expressions of glucose-regulated protein 78（ GRP78）,phosphorylated protein kinase receptorlike endoplasmic reticulum kinase（ p-PERK）,phosphorylated eukaryotic translation initiation factor（ p-eIF2α）,transcription factors C/EBP homologue protein（ CHOP）,inositol-requiring enzyme 1α（ IRE1α） and X-box binding protein 1（ XBP1） in lung tissue were determined by Western blotting. Results： Compared with control group,rats in both low dose（ 5 mg/kg） and high dose（ 25 mg/kg）PM2.5-treated groups showed obviously dose-dependent pulmonary toxicity including thickening of alveolar walls,narrowing of alveolar space,interstitial hyperplasia and inflammatory cell infiltration. Compared with control group,T-AOC level and the SOD activity in BALF in both PM2.5-treated groups were decreased dose-dependently（ P〈0.05）,whereas the LDH activity in BALF were increased in a dose-dependent manner（ P〈0.05）. Exposure to PM2.5 resulted in a increasing of the release of proinflammatory cytokines including TNF-α,IL-1β and IL-6 in rat lung in a dose-dependent manner（ P〈0.05）. The levels of GRP78,p-PERK,p-eIF2α,CHOP,IRE1αand spliced XBP1（ XBP1-S） were significantly up-regulated,whereas the level of unspliced XBP1（ XBP1-U） was down-regulated in the rat lung tissue of high-dose PM2.5 treated group. Conclusion： The PM2.5 in the urban area of Hangzhou can significantly cause lung inflammatory injury in rats. Both oxidative stress and activation of ER stress pathways may be related to such PM2.5 inhalation-induced lung inflammatory injury.