2015年北京市空气质量指数及PM2.5浓度对鼻出血发病率的影响

摘要：目的探讨鼻出血的发病率与PM2.5浓度之间的关系,分析除自身因素以外,环境因素特别是空气质量以及大气中PM2.5浓度对鼻出血发病率的影响。方法收集2015年北京同仁医院急诊就诊鼻出血患者数量,北京市空气质量指数（air quality index, AQI）和大气中细颗粒污染物PM2.5浓度,统计鼻出血数量与PM2.5浓度之间的关系;按空气质量指数将全部数据进行分组,统计各组之间鼻出血发病率之间的差异。结果鼻出血的发病率与PM2.5之间呈正相关(r=0.261);当空气质量达到重度污染时,鼻出血的发病率比空气质量为优良时明显增加,差异具有统计学意义（P<0.05）。结论PM2.5浓度的增加可能是鼻出血发病的一个健康风险因素。     

The Cellular Toxicity of PM2.5 Emitted from Coal Combustion in Human Umbilical Vein Endothelial Cells

ObjectiveTo explore the relationship between different components offineparticulate matter (PM2.5) emitted from coal combustion and their cytotoxic effect in the vascular endothelial cells. MethodsCoal-fired PM2.5was sampled using a fixed-source dilution channel and flow sampler. The sample components were analyzed by ion chromatography and inductively coupled plasma atomic emission spectroscopy(ICP-AES). The PM2.5suspension was extracted using an ultrasonic water-bath method and thenhuman umbilical vein endothelial cells (EA.hy926) were treated withvarious concentrations of the PM2.5 suspension. Cell proliferation,oxidativeDNA damage, and global DNA methylation levelswere used to measurethe cellulartoxicity of PM2.5emitted fromcoalcombustion. ResultsComparedtoothertypesof coal-fired PM2.5preparations,thePM2.5 suspension from Yinchuan coal had the highest cytotoxicity.PM2.5 suspension from Datong coal hadthe highest toxic effectwhile that fromYinchuan coal had the lowest.Exposure to coal-fired PM2.5 from Jingxi coalresulted inlower 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. At the same dose, PM2.5 emitted from coal combustion could produce more severeDNAimpairmentcompared to that produced by carbon black.Cell survival rate was negatively correlated with chloride and potassiumionscontent.The5-methylcytosine(5-mC) level waspositively correlated withMnandnegatively correlated withZn levels.The 8-OHdG% level was positively correlated withboth MnandFe. ConclusionPM2.5 emitted from coal combustion can decrease cell viability, increase global DNA methylation, and causeoxidativeDNA damage inEA.hy926 cells. Metalcomponentsmay be important factors that influence cellular toxicity.     

Nasal epithelial barrier disruption by particulate matter ≤2.5 μm via tight junction protein degradation

Upper airway diseases including sinonasal disorders may be caused by exposure to fine particulate matter (≤2.5 μm; PM2.5), as proven by epidemiological studies. PM2.5 is a complex entity whose chemical constituents and physicochemical properties are not confined to a single, independent “particle” but which in this study means a distinctive environmental “toxin.” The mechanism whereby PM2.5 induces nasal epithelial barrier dysfunction leading to sinonasal pathology remains unknown. In the present study, human nasal epithelial cells were exposed to non‐cytotoxic doses of PM2.5 to examine how PM2.5 affects the nasal epithelial barrier. Tight junction (TJ) integrity and function were assessed by transepithelial electric resistance and paracellular permeability. The expression levels of TJ proteins such as zona occludens‐1, occludin and claudin‐1 were assessed by immunofluorescence staining and western blot. PM2.5 exposure induced epithelial barrier dysfunction as reflected by increased paracellular permeability and decreased transepithelial electric resistance. TJ proteins zona occludens‐1, occludin and claudin‐1 were found to be downregulated. Pretreatment with N‐acetyl‐l ‐cysteine alleviated PM2.5‐mediated reactive oxygen species generation in RPMI 2650 cells, further preventing barrier dysfunction and attenuating the degradation of TJ proteins. These results suggest that PM2.5 induces nasal epithelial barrier disruption via oxidative stress, and N‐acetyl‐l ‐cysteine counteracts this PM2.5‐mediated effect. Thus, nasal epithelial barrier disruption caused by PM2.5, which leads to sinonasal disease, may be prevented or treated through the inhibition of reactive oxygen species.     

Resveratrol relieves particulate matter (mean diameter < 2.5 μm)‐induced oxidative injury of lung cells through attenuation of autophagy deregulation

Oxidative stress and inflammation are critically implicated in ambient fine particulate matter (mean diameter < 2.5 μm; PM_2.5)‐induced lung injury. Autophagy, playing a crucial role in various physiopathological conditions, modulates cellular homeostasis and stress adaptation. Resveratrol is a phytoalexin that exerts potent antioxidant effects on cardiopulmonary diseases. To date, the mechanisms by which resveratrol protects against PM_2.5 remain to be elucidated. In the present study, we investigated the effect of resveratrol on PM_2.5‐induced oxidative injury. The potential role of nuclear factor erythroid‐2‐related factor 2 and autophagy in this progress was explored. Human bronchial epithelial cells were treated with PM_2.5 and the cytotoxicity and oxidative stress markers were determined. The results showed that PM_2.5 decreased cell viability and elevated the level of lactate dehydrogenase. The levels of malondialdehyde and reactive oxygen species were increased by PM_2.5 exposure. PM_2.5 also induced a significant increase of the inflammatory cytokines including interleukin (IL)‐6, IL‐8, IL‐1β and tumor necrosis factor α. Meanwhile, PM_2.5 triggered autophagy formation and alteration of the nuclear factor erythroid‐2‐related factor 2 pathway. Furthermore, human bronchial epithelial cells were co‐treated with PM_2.5 and resveratrol in the presence or absence of 3‐methylamphetamine, an inhibitor of autophagic formation. It was revealed that resveratrol intervention abolished PM_2.5‐induced oxidative injury partially through the suppression of autophagy deregulation. Findings from this study could provide new insights into the molecular mechanisms of pulmonary intervention during PM_2.5 exposure.     

阿魏酸对大气细颗粒物PM2.5诱导的小鼠主动脉炎症的干预作用

目的 探讨大气细颗粒物PM2.5对小鼠主动脉Toll样受体（Toll-like receptors,TLRs）信号通路的影响及阿魏酸的干预作用。方法 采用气管滴注方法以10,20 mg·kg^-1的PM2.5处理小鼠,并用40,80 mg·kg^-1的阿魏酸对部分20 mg·kg^-1 PM2.5处理后的小鼠进行治疗。2周后处死小鼠,血液细胞分析仪检测小鼠血液中炎症细胞水平,ELISA检测血清中IL-1β和IL-6的含量,并用荧光定量PCR检测主动脉中IL-1β和IL-6的mRNA水平,Western blot检测各组小鼠主动脉组织中TLR2、TLR4、MyD88、NF-κB p65蛋白的表达,免疫组化技术观察TLR2和TLR4在小鼠主动脉中的水平。结果 PM2.5能提高血液中NEUT、EOS的数量及其在总细胞中的比率,增加血液和主动脉组织中炎症因子IL-1β、IL-6的含量,上调主动脉组织中的TLRs通路相关分子TLR2、TLR4、MyD88、NF-κB p65的表达;而用阿魏酸干预后,血液中白细胞数量、EOS数量、NEUT与EOS的比率明显降低,IL-1β、IL-6水平下降。同时主动脉组织中的TLRs通路相关分子的表达下调。结论 PM2.5可能通过TLRs通路诱导小鼠主动脉炎症的产生,而阿魏酸可能通过抑制TLRs通路相关因子的表达而发挥抑制PM2.5诱导的小鼠主动脉炎症的作用。     

MiR‐146a regulates PM1‐induced inflammation via NF‐κB signaling pathway in BEAS‐2B cells

Exposure to particulate matter (PM) leads to kinds of cardiopulmonary diseases, such as asthma, COPD, arrhythmias, lung cancer, etc., which are related to PM‐induced inflammation. We have found that PM_2.5 (aerodynamics diameter <2.5 µm) exposure induces inflammatory response both in vivo and in vitro. Since the toxicity of PM is tightly associated with its size and components, PM₁ (aerodynamics diameter <1.0 µm) is supposed to be more toxic than PM_2.5. However, the mechanism of PM₁‐induced inflammation is not clear. Recently, emerging evidences prove that microRNAs play a vital role in regulating inflammation. Therefore, we studied the regulation of miR‐146a in PM₁‐induced inflammation in human lung bronchial epithelial BEAS‐2B cells. The results show that PM₁ induces the increase of IL‐6 and IL‐8 in BEAS‐2B cells and up‐regulates the miR‐146a expression by activating NF‐κB signaling pathway. Overexpressed miR‐146a prevents the nuclear translocation of p65 through inhibiting the IRAK1/TRAF6 expression, and downregulates the expression of IL‐6 and IL‐8. Taken together, these results demonstrate that miR‐146a can negatively feedback regulate PM₁‐induced inflammation via NF‐κB signaling pathway in BEAS‐2B cells.     

Ultrafine particulate matter exposure impairs vasorelaxant response in superoxide dismutase 2-deficient murine aortic rings

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease antioxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2-deficient (SOD2^+/–) mice that possess decreased antioxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2^+/– mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2^+/– mouse aortas, and relaxation was significantly reduced in young SOD2^+/– compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2^+/– mice. Data demonstrated that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of antioxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2^+/– mice.

Abbreviations: H₂O₂: hydrogen peroxide; NTG: nitroglycerin; PAH: polycyclic aromatic hydrocarbons; PE: l-phenylephrine; PM: particulate matter; ROS: reactive oxygen species; SOD2: superoxide dismutase 2 deficient; WT: wild type     

Water‐insoluble fraction of airborne particulate matter (PM10) induces oxidative stress in human lung epithelial A549 cells

Exposure to ambient airborne particulate matter (PM) with an aerodynamic diameter less than 10 μm (PM₁₀) links with public health hazards and increases risk for lung cancer and other diseases. Recent studies have suggested that oxidative stress is a key mechanism underlying the toxic effects of exposure to PM₁₀. Several components of water‐soluble fraction of PM₁₀ (sPM₁₀) have been known to be capable of inducing oxidative stress in in vitro studies. In this study, we investigated if water‐insoluble fraction of PM₁₀ (iPM₁₀) could be also capable of inducing oxidative stress and oxidative damage. Human lung epithelial A549 cells were exposed to 10 μg/mL of sPM₁₀, iPM₁₀ or total PM₁₀ (tPM₁₀) preparation for 24 h. Here, we observed that all three PM₁₀ preparations reduced cell viability and induced apoptotic cell death in A549 cells. We further found that, similar to the exposure to sPM₁₀ and tPM₁₀, the intracellular level of hydrogen peroxide (H₂O₂) in the iPM₁₀‐exposed cells was increased significantly; meanwhile the activity of catalase was decreased significantly as compared with the unexposed control cells, resulting in significant DNA damage. Our data obtained from inductively coupled plasma‐mass spectrometry (ICP‐MS) assays showed that iron is the most abundant metal in all three PM₁₀ preparations. Thus, we have demonstrated that, similar to sPM₁₀, iPM₁₀ is also capable of inducing oxidative stress by probably inducing generation of H₂O₂ and impairing enzymatic antioxidant defense, resulting in oxidative DNA damage and even apoptotic cell death through the iron‐catalyzed Fenton reaction. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 226–233, 2014.     

Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation.