含葡聚糖颗粒物暴露致小鼠肺部GSNO还原酶活化的研究  

Induction of GSNO Reductase in the Lungs of Mice Exposed to Glucan-Spiked Dust

作　　者：秦晓丹[1] 柯玉洁[1] 周鄂生[2] 曹毅[3] 丁书茂[1] 杨旭[1] 

机构地区：[1]华中师范大学生命科学学院遗传调控和整合生物学湖北省重点实验室,430079 [2]华中师范大学校医院公共卫生科 [3]丹麦哥本哈根大学公共卫生学院

出　　处：《玉林师范学院学报》2011年第2期2-6,共5页Journal of Yulin Normal University

基　　金：国家自然科学基金面上项目(51076079)

摘　　要：动物实验和体外研究都已表明,空气中有机颗粒物可引起肺部炎症反应,该反应的显著特点为细胞因子表达上调和分泌增多.葡聚糖是霉菌和细菌代谢及裂解的产物,当颗粒物受到霉菌和细菌污染之后,就会含有葡聚糖.最近的研究表明,含葡聚糖颗粒物的暴露会影响鼻腔和肺部的功能,并伴随炎症反应.然而,含葡聚糖颗粒物的暴露对一氧化氮合酶(NOS)和亚硝基谷胱甘肽还原酶(GSNOR)的影响仍不太清楚.本研究旨在检测含葡聚糖颗粒物暴露对呼吸道中NO信号通路的影响.本实验力小鼠被分别暴露于20μL PBS(空白组),20μL浓度为25μg/20μL的OVA和20μL浓度为100μL/20μL的含葡聚糖颗粒物环境中,暴露持续12d.暴露结束后在肺组织匀浆中检测NOS和GSNOR的活性.同时测定肺组织中谷胱甘肽(GSH)浓度和SOD活性用以评估氧化应激水平.另外,检测肺组织中的IL–6浓度确定炎症反应的发生与否.结果显示,12天OVA和葡聚糖颗粒物暴露并未明显影响NOS活性、GSH含量、SOD活性和IL-6浓度.然而,含葡聚糖颗粒物12d的暴露却明显增加GSNOR的活性和表达.我们的研究结果表明,含葡聚糖颗粒物暴露会激活呼吸道中的GSNOR,但不激活NOS.由于GSNOR在NO信号通路中起着举足轻重的作用,我们的研究结果具有一定的临床重要性.Both animal experiment and in vitro studies have suggested that airborne organic dusts may induce inflammatory responses in the lungs,characterized by typical patterns of cytokine up-regulation and secretion.Glucan is the product of mildew and bacteria’s metabolism and cracking.When the particulate is polluted by mildew and bacteria,it will contain beta-glucan.Recent work showed that exposure to glucan-spiked dust might influence nasal and pulmonary function,without an accompanying inflammatory response.However,effects of glucan-spiked dust exposure on NOS and GSNO reductase（enzymes important to NO signaling） remain less clear.This study aims to determine the effects of simultaneous exposure to glucan-spiked dust on NO signaling pathway in the airway.Mice were exposed to 20μL PBS（controls）,20 μL 25 μg/20 μL OVA and 20 μL 100 μg/20 μL glucan-spiked dust,respectively,daily for 12 days.NOS and GSNO reductase activity were measured in lung homogenate.Glutathione concentration and SOD activity in lung tissue were also determined to evaluate changes in oxidative stress.IL-6 concentration was measured in lungs to quantify the inflammatory response.Results showed that 12 day OVA and glucan-spiked dust exposure did not significantly influence NOS activity,GSH concentration,SOD activity,or IL-6 concentration.An insignificant increase in GSNOR activity and expression was observed in 12 day OVA-exposed mice,whereas glucan-spiked dust exposure significantly increased GSNOR activity and expression.Our results suggested that repeated glucan-spiked dust exposure to the airway could activate GSNO reductase but not NOS.Since GSNO reductase plays a pivotal role in NO signaling,these results may have clinical reference.

关 键 词：含葡聚糖颗粒物 亚硝基谷胱甘肽还原酶(GSNOR) 一氧化氮(NO) 一氧化氮合酶(NOS) 

分 类 号：X174[环境科学与工程—环境科学]