DEHP对哮喘模型大鼠气道高反应性和肺嗜酸性粒细胞浸润的影响

为探讨邻苯二甲酸二乙基己酯[di-(2-ethylhexyl)phthalate,DEHP]在诱发哮喘和哮喘发病机理方面的作用,将Wistar大鼠随机分为正常组、卵清白蛋白(OVA)致敏组和DEHP染毒组,每组8只.用OVA致敏加激发的方法制作大鼠哮喘模型.DEHP染毒组分为2个组,每天分别给予0.7mg·kg-1和70mg·kg-1邻苯二甲酸二乙基己酯灌胃,连续30d.OVA致敏组、DEHP染毒组大鼠均在第31d给予1%OVA雾化,诱发哮喘.第38d测定大鼠在不同氯化乙酰甲胆碱(MCH)剂量下的肺功能,进行支气管肺泡灌洗液(BALF)的嗜酸性粒细胞(EOS)计数.结果显示,与OVA组相比,DEHP染毒组气道高反应性增强,嗜酸性粒细胞比例明显增多(P<0.01).因此,邻苯二甲酸二乙基己酯可增强哮喘模型大鼠气道高反应性和嗜酸性粒细胞浸润,可诱导哮喘的发生.     

Control chart for monitoring occupational asthma

INTRODUCTION: Work-related asthma has become the most prevalent occupational respiratory disease in the developed world. Occupational asthma is thought to affect 5%-10% of people worldwide. The first step in the diagnosis of occupational asthma is to establish work-relatedness. Although considerable research has been conducted in the area of occupational asthma, no simple, effective, and statistically sound method has been developed that can be used as an initial step to effectively identify the workers at risk for occupational asthma. The purpose of this research was to investigate whether Shewhart control chart method can be used as an effective method to detect occupational asthma. METHOD: Forty-five workers who completed the study and provided usable peak expiratory flow (a lung function marker) recordings while at work and away from work were included in this study. Control charts were developed using Shewhart's Method. The lower control limit of at work control chart (LCL(W)) was compared to each subject's Personal Best (PB) value. RESULTS: Reviewing the results of this comparison showed LCL(W)<60% PB to have a sensitivity of 85.71%, specificity of 87.50%, and an error rate of 13.33%. When the subjects suspected for false positive and false negative diagnoses were identified, the test produced a sensitivity of 95.24%, a specificity of 95.83% and an error rate of 4.44%. CONCLUSIONS: Our results were as good as, and in some cases better than, published clinical guidelines. IMPACT ON INDUSTRY: Our research showed that the control chart method is an effective, simple, and inexpensive tool for early intervention in workers suspected for occupational asthma.     

过敏与非过敏儿童室内PM2.5的细胞毒性比较研究

流行病学研究表明,空气细颗粒污染物(PM_(2.5))的暴露与过敏性疾病有一定的联系;然而,PM_(2.5)暴露与过敏性疾病之间的关系尚未完全阐明,特别是室内环境中PM_(2.5)涉及到过敏或非过敏的作用不详.为了比较研究过敏与非过敏儿童室内PM_(2.5)的细胞毒性,在武汉市洪山区10户家庭室内进行了为期3个月的采样,分别收集过敏与非过敏儿童的室内PM_(2.5).采用有机/元素碳测定仪对二者PM_(2.5)成分中的含碳组分进行了分析,并通过检测昆明小鼠巨噬细胞的形态及吞噬功能影响、细胞活力、乳酸脱氢酶(LDH)漏出率等指标,来检测PM_(2.5)暴露所致的细胞毒性.结果表明,高剂量(200μg·mL~(-1))PM_(2.5)暴露对小鼠巨噬细胞的形态及吞噬功能会产生不利的影响;与非过敏儿童的室内PM_(2.5)暴露组相比,过敏儿童的室内PM_(2.5)暴露组诱导巨噬细胞产生的毒性作用更明显.细胞体外测试结果提示:在相同PM_(2.5)暴露剂量下,引起儿童过敏症的室内PM_(2.5)成分具有重要影响.     

Landlords,fear, and children's respiratory health: an untold story of environmental injustice in the central city

Recent research has explored the role of environmental inequalities in explaining health disparities, especially in urban environments. This paper investigates the role of the landlord in shaping indoor environmental injustices. Specifically, we rely on interview data from low-income parents in South Phoenix, AZ, with elementary-aged children with asthma. We found families living in poor quality rental housing that impacted children's breathing. Landlords were directly involved in keeping the homes in poor condition, even when asked by the tenant to fix the property, and immigrants were especially at risk. In general, relationships between landlords and tenants were unequal and coloured by the tenant's poverty and fears of eviction. Among the immigrant tenants, many had accompanying fears of authorities and deportation. The cycle of fear, poverty, and a lack of power compounded as tenants were hesitant to report problems, which reinforced the power of the landlord over the tenant and did nothing to improve living conditions. Recognising the role of landlords in creating substandard housing conditions is important as they represent a group that can be targeted for interventions.     

甲醛暴露时间延长加剧小鼠哮喘模型肺氧化损伤并促进IL-17表达

为了探究不同暴露时间甲醛对小鼠哮喘模型肺氧化应激及IL-17表达的影响,用浓度为3.0 mg·m~(-3)的甲醛气体吸入染毒,同时将48只雄性Balb/c小鼠随机分为6组:(1)对照组(生理盐水组);(2)ovalbumin(OVA)致敏组;(3)0.5 h甲醛+OVA组;(4)1h甲醛+OVA组;(5)1.5 h甲醛+OVA组;(6)2 h甲醛+OVA组,以不同时间长度进行甲醛暴露,连续35 d。OVA致敏组、0.5 h甲醛+OVA组、1 h甲醛+OVA组、1.5 h甲醛+OVA组、2 h甲醛+OVA组均在第11、18及25天腹腔注射OVA致敏液(5 mg OVA+175 mg Al(OH)_3+30 mL生理盐水),第29~35天(共计1周)进行1%OVA雾化(30 min·d~(-1)),每日1次,诱发哮喘。第36天进行以下操作:取肺组织测定肺系数并制作肺匀浆,检测肺组织中活性氧自由基(ROS)、丙二醛(MDA)和还原型谷胱甘肽(GSH)的含量,并采用ELISA法检测肺组织中IL-17的水平。同时,采用HE染色法观察小鼠肺部气道的病理学变化。结果显示,在浓度为3.0 mg·m~(-3)的甲醛气体吸入染毒条件下,与对照组相比,1.5 h甲醛+OVA染毒组、2 h甲醛+OVA染毒组ROS、MDA、IL-17含量上升,具有统计学意义(P0.01)。同时,随着暴露时间长度的增加,小鼠肺部气道出现明显病理学变化。综上所述,每天2 h甲醛+OVA染毒能对小鼠肺造成损伤并恶化OVA对小鼠肺的损伤,产生炎症反应,并通过氧化应激反应介导。     

DINP皮肤暴露对小鼠过敏性皮肤炎症的佐剂作用

为了探究新型增塑剂邻苯二甲酸二异壬酯(DINP)对小鼠过敏性皮肤炎症的影响,采用皮肤染毒的暴露方式,56只SPF级雄性Balb/C小鼠随机平均分为7组处理40d.用0、1.4、14和140mg/kg DINP对小鼠进行皮肤染毒,并用抗氧化剂褪黑素设置2组来探究氧化应激的介导作用,以及1组生理盐水对照组.染毒结束后取耳组织测定耳肿指数和双耳重量差,并制作耳组织病理学切片,最后检测氧化应激指标.实验结果显示, 14和140mg/kg DINP皮肤暴露组的皮肤炎症有明显加剧(P<0.01),氧化应激指标也有明显变化(P <0.01).这表明,一定浓度的DINP,经较长时间的暴露,对小鼠过敏性皮肤炎症具有明显的佐剂作用.并且,随着DINP浓度升高,小鼠机体氧化应激过度活化,造成机体组织或细胞的氧化损伤,并加剧了炎症反应.     

Monitoring Nitrogen Dioxide and its Effects on Asthmatic Patients: Two Different Strategies Compared

Objectives: To develop a `methodologyassessment' to evaluate the strengths and theweaknesses of two different epidemiological approachesand to identify the best suited monitoring strategy tomeasure the effects of `normal levels' of nitrogendioxide exposure on the health of an urban population.Methodology: all exposures to nitrogen dioxidewere determined with passive samplers, each samplerconsisting of 3 measuring Palmes tubes. In the firststudy the nitrogen dioxide exposure was assessed in 23school children (11 asthmatic and 12 non asthmatic).Children wore samplers for a week and parallelmeasurements were made in their kitchens, in bedroomsand outside their homes. The second study consisted ina case-control study where the relative risk ofhospital admission was calculated considering nitrogendioxide levels in a city of northern Italy. 110asthmatic patients were compared to a control group of 5322 people.Results: Personal sampler measurementshighlighted significant differences in exposure when nitrogen dioxide atmospheric levels were compared inasthmatic and healthy children (p<0.05). No otherparameters were significant in the two groups. Asignificant action of atmospheric nitrogen dioxide onhospital admission was demonstrated (p<0.01).Conclusions: Although a cause-effect relation assuch cannot be identified, the studies show a relationbetween the exposure to nitrogen dioxide and thepresence of adverse effects on people's health.However the `disadvantage' is for subjects withasthmatic pathologies, compared to the others. Tomanage this problem most effectively, a combinedapproach with the activation of specific personalmonitoring campaigns of the subjects with verifiedrisk seems necessary. This requires `reading' the dataresulting from most extensive and up to dateinformation systems, capable of a thorough controlboth of the living environment and of the clinicaloutcome of the whole population.     

大气PM2.5及高脂饮食对哮喘发病影响的研究进展

大气PM_2.5暴露与呼吸系统疾病密切相关,高脂饮食是哮喘的诱因之一.近年来,哮喘发病率在我国呈上升趋势.对大气PM_2.5、高脂饮食及二者协同作用对哮喘发病的影响进行探讨,为哮喘的干预和治疗提供新思路.总结了PM_2.5暴露与高脂饮食对哮喘的影响以及哮喘的发病机制:①颗粒物暴露可引发机体炎症反应,增加哮喘发病风险;②高脂饮食可通过代谢活化机体内免疫相关信号通路,导致炎症发生;③二者均会通过MyD88/TLRs信号通路和Th1/Th2机制对哮喘炎症产生影响.研究显示,PM_2.5与高脂饮食对哮喘的作用机制具有一致性,二者对人群的健康影响可能具有协同作用.      

北京市石景山区PM2.5中典型水溶性离子分布特征及其致敏效应研究

为了考察大气细颗粒物水溶性成分与过敏性疾病的相关性,对北京市石景山区PM_2.5中水溶性离子分布特征进行分析,对文献中报道的有机酸浓度进行总结,选取其中9种典型水溶性无机盐（硝酸铵、硫酸铵、氯化铵、硝酸钠、无水硫酸钠、硝酸钾、硫酸钾、硝酸钙、硫酸钙）及3种水溶性有机酸（丙二酸、丁二酸、乙二酸）进行肥大细胞激活实验,观察上述成分经IgE及非IgE途径对肥大细胞β-Hex释放率的影响.结果表明：铵离子、硝酸离子和硫酸离子是研究区PM_2.5中占比最大的3种离子,丙二酸、丁二酸、乙二酸是北京市PM_2.5中3种浓度较高的水溶性有机酸.非IgE途径下,100μg·mL^-1的9种水溶性无机盐和80μg·mL⁽-1(的3种水溶性有机酸均无法提高肥大细胞β-Hex释放率.IgE途径下,仅观察到80μg·mL^-1丙二酸能使肥大细胞β-Hex释放率提高约3%,其增敏作用还需进一步研究证实.本研究将为进一步研究PM_2.5水溶性成分诱发或加重过敏性疾病的潜在机制...     

邻苯二甲酸二乙基己酯(DEHP)对THP-1细胞IL-1β和MMP-8表达及ROS的影响

为探讨邻苯二甲酸二乙基己酯((DEHP)的细胞免疫毒性作用与机制,采用RT-PCR和ELISA方法,考察了0.05～1μmol·L-1浓度范围内的DEHP对THP-1细胞白细胞介素-1β(IL-1β)及基质金属蛋白酶-8(MMP-8)基因和蛋白表达的影响;采用免疫印迹WesternBlot方法检测DE-HP对ERK1/2磷酸化水平的影响;以2,'7-'二氯荧光素二乙酸酯(DCFH-DA)为荧光探针检测1～50μmol·L-1DEHP对细胞内活性氧(ROS)产生的影响。结果显示,0.05和0.2μmol·L-1DEHP在6h内显著诱导IL-1β和MMP-8基因表达(P<0.05或0.01);0.05～1μmol·L-1DEHP刺激细胞48h,可诱导IL-1β蛋白表达,并表现出明显的剂量-效应关系,线性拟合的确定系数为0.937;0.05μmol·L-1DEHP刺激细胞6或12h,显著诱导MMP-8蛋白表达(P<0.05);0.2μmol·L-1DEHP在15～30min内快速诱导ERK1/2磷酸化;1～50μmol·L-1DEHP浓度依赖性刺激细胞中ROS的产生;ERK/MAPK抑制剂PD98059显著抑制DEHP诱导的MMP-8分泌,但对IL-1β分泌未表现出抑制作用。研究表明,DEHP可能是经ERK/MAPK信号路径诱导MMP-8基因和蛋白的表达,经其他路径诱导IL-1β基因和蛋白的表达,诱导细胞内ROS的产生,从而激发炎症反应,进而损害免疫系统功能引发哮喘等炎症性疾病。此研究结果可为DEHP的暴露风险评估提供参考。