Ruscogenin attenuates particulate matter-induced acute lung injury in mice via protecting pulmonary endothelial barrier and inhibiting TLR4 signaling pathway

The inhalation of particulate matter (PM) is closely related to respiratory damage, including acute lung injury (ALI), characterized by inflammatory fluid edema and disturbed alveolar-capillary permeability. Ruscogenin (RUS), the main active ingredient in the traditional Chinese medicine Ophiopogonis japonicus, has been found to exhibit anti-inflammatory activity and rescue LPS-induced ALI. In this study, we investigated whether and how RUS exerted therapeutic effects on PM-induced ALI. RUS (0.1, 0.3, 1 mg·kg⁻¹·d⁻¹) was orally administered to mice prior to or after intratracheal instillation of PM suspension (50 mg/kg). We showed that RUS administration either prior to or after PM challenge significantly attenuated PM-induced pathological injury, lung edema, vascular leakage and VE-cadherin expression in lung tissue. RUS administration significantly decreased the levels of cytokines IL-6 and IL-1β, as well as the levels of NO and MPO in both bronchoalveolar lavage fluid (BALF) and serum. RUS administration dose-dependently suppressed the phosphorylation of NF-κB p65 and the expression of TLR4 and MyD88 in lung tissue. Furthermore, TLR4 knockout partly diminished PM-induced lung injury, and abolished the protective effects of RUS in PM-instilled mice. In conclusion, RUS effectively alleviates PM-induced ALI probably by inhibition of vascular leakage and TLR4/MyD88 signaling. TLR4 might be crucial for PM to initiate pulmonary lesion and for RUS to exert efficacy against PM-induced lung injury.     

Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress,vagal dominance,arrhythmia and pulmonary inflammation in heart failure-prone rats

Abstract

Acute exposure to ambient fine particulate matter (PM_2.5) is tied to cardiovascular morbidity and mortality, especially among those with prior cardiac injury. The mechanisms and pathophysiological events precipitating these outcomes remain poorly understood but may involve inflammation, oxidative stress, arrhythmia and autonomic nervous system imbalance. Cardiomyopathy results from cardiac injury, is the leading cause of heart failure, and can be induced in heart failure-prone rats through sub-chronic infusion of isoproterenol (ISO). To test whether cardiomyopathy confers susceptibility to inhaled PM_2.5 and can elucidate potential mechanisms, we investigated the cardiophysiologic, ventilatory, inflammatory and oxidative effects of a single nose-only inhalation of a metal-rich PM_2.5 (580?µg/m³, 4?h) in ISO-pretreated (35 days?×?1.0?mg/kg/day sc) rats. During the 5 days post-treatment, ISO-treated rats had decreased HR and BP and increased pre-ejection period (PEP, an inverse correlate of contractility) relative to saline-treated rats. Before inhalation exposure, ISO-pretreated rats had increased PR and ventricular repolarization time (QT) and heterogeneity (Tp-Te). Relative to clean air, PM_2.5 further prolonged PR-interval and decreased systolic BP during inhalation exposure; increased tidal volume, expiratory time, heart rate variability (HRV) parameters of parasympathetic tone and atrioventricular block arrhythmias over the hours post-exposure; increased pulmonary neutrophils, macrophages and total antioxidant status one day post-exposure; and decreased pulmonary glutathione peroxidase 8 weeks after exposure, with all effects occurring exclusively in ISO-pretreated rats but not saline-pretreated rats. Ultimately, our findings indicate that cardiomyopathy confers susceptibility to the oxidative, inflammatory, ventilatory, autonomic and arrhythmogenic effects of acute PM_2.5 inhalation.     

Foam cell formation by particulate matter (PM) exposure: a review

Increasing evidence suggests that exposure of particulate matter (PM) from traffic vehicles, e.g., diesel exhaust particles (DEP), was associated with adverse vascular effects, e.g., acceleration of atherosclerotic plaque progression. By analogy, engineered nanoparticles (NPs) could also induce similar effects. The formation of lipid laden foam cells, derived predominately from macrophages and vascular smooth muscle cells (VSMC), is closely associated with the development of atherosclerosis and adverse vascular effects. We reviewed current studies about particle exposure-induced lipid laden foam cell formation. In vivo studies using animal models have shown that exposure of air pollution by PM promoted lipid accumulation in alveolar macrophages or foam cells in plaques, which was likely associated with pulmonary inflammation or systemic oxidative stress, but not blood lipid profile. In support of these findings, in vitro studies showed that direct exposure of cultured macrophages to DEP or NP exposure, with or without further exposure to external lipids, promoted intracellular lipid accumulation. The mechanisms remained unknown. Although a number studies found increased reactive oxygen species (ROS) or an adaptive response to oxidative stress, the exact role of oxidative stress in mediating particle-induced foam cell formation requires future research. There is currently lack of reports concerning VSMC as a source for foam cells induced by particle exposure. In the future, it is necessary to explore the role of foam cell formation in particle exposure-induced atherosclerosis development. In addition, the formation of VSMC derived foam cells by particle exposure may also need extensive studies.     

Toxicity of inhaled particulate matter on the central nervous system: neuroinflammation,neuropsychological effects and neurodegenerative disease

Particulate matter (PM) combined with meteorological factors cause the haze, which brings inconvenience to people's daily life and deeply endanger people's health. Accumulating literature, to date, reported that PM are closely related to cardiopulmonary disease. Outpatient visits and admissions as a result of asthma and heart attacks gradually increase with an elevated concentration of PM. Owing to its special physicochemical property, the brain could be a potential target beyond the cardiopulmonary system. Possible routes of PM to the brain via a direct route or stimulation of pro‐inflammatory cytokines have been reported in several documents concerning toxicity of engineered nanoparticles in rodents. Recent studies have demonstrated that PM have implications in oxidative stress, inflammation, dysfunction of cellular organelles, as well as the disturbance of protein homeostasis, promoting neuron loss and exaggerating the burden of central nervous system (CNS). Moreover, the smallest particles (nano‐sized particles), which were involved in inflammation, reactive oxygen species (ROS), microglial activation and neuron loss, may accelerate the process of the neurodevelopmental disorder and neurodegenerative disease. Potential or other undiscovered mechanisms are not mutually exclusive but complementary aspects of each other. Epidemiology studies have shown that exposure to PM could bring about neurotoxicity and play a significant role in the etiology of CNS disease, which has been gradually corroborated by in vivo and in vitro studies. This review highlights research advances on the health effects of PM with an emphasis on neurotoxicity. With the hope of enhancing awareness in the public and calling for prevention and protective measures, it is a critical topic that requires proceeding exploration. Copyright © 2017 John Wiley & Sons, Ltd.     

Rat lung response to ozone and fine particulate matter (PM2.5) exposures

Exposure to different ambient pollutants maybe more toxic to lung than exposure to a single pollutant. In this study, we discussed the inflammation and oxidative stress responses of rat lung caused by ozone and PM_2.5 versus that of rats exposed to saline, ozone, or single PM_2.5. Wistar rats inhaled 0.8 ppm ozone or air for 4 h and then placed in air for 3 h following intratracheal instillation with 0, 0.2 (low dose), 0.8 (medium dose), 3.2 (high dose) mg/rat PM_2.5 dissolved in sterile saline (0.25 mL/rat), repeated twice per week for 3 weeks, the cumulative doses of PM_2.5 in animals were 1.2, 4.8, and 19.2 mg. Rats were sacrificed 24 h after the last (sixth) exposure. The collected bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cells and cytokines. Lung tissues were processed for light microscopic and transmission electron microscopic (TEM) examinations. Results showed that total cell number in BALF of PM_2.5‐exposed groups were higher than control (p < 0.05). PM_2.5 instillation caused dose‐trend increase in tumor necrosis factor alpha (TNF‐α), interleukin‐6, lactate dehydrogenase, and total protein of BALF. Exposure to ozone alone only caused TNF‐α significant change in above‐mentioned indicators of lung injury. On the other hand, ozone could enhance PM_2.5‐induced inflammatory changes and pathological characters in rat lungs. SOD and GSH‐Px activities in lung were reduced in PM_2.5‐exposed rats with and without prior ozone exposure compared to control. To determine whether the PM_2.5 and ozone affect endothelium system, iNOS, eNOS, and ICAM‐1 mRNA levels in lung were analyzed by real‐time PCR. These data demonstrated that inflammation and oxidative stress were involved in toxicology mechanisms of PM_2.5 in rat lung and ozone potentiated these effects induced by PM_2.5. These results have implications for understanding the pulmonary effects induced by ozone and PM_2.5. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 343–356, 2015.     

Differential pulmonary and cardiac effects of pulmonary exposure to a panel of particulate matter-associated metals

Biological mechanisms underlying the association between particulate matter (PM) exposure and increased cardiovascular health effects are under investigation. Water-soluble metals reaching systemic circulation following pulmonary exposure are likely exerting a direct effect. However, it is unclear whether specific PM-associated metals may be driving this. We hypothesized that exposure to equimolar amounts of five individual PM-associated metals would cause differential pulmonary and cardiac effects. We exposed male WKY rats (14 weeks old) via a single intratracheal instillation (IT) to saline or 1 μmol/kg body weight of zinc, nickel, vanadium, copper, or iron in sulfate form. Responses were analyzed 4, 24, 48, or 96 h after exposure. Pulmonary effects were assessed by bronchoalveolar lavage fluid levels of total cells, macrophages, neutrophils, protein, albumin, and activities of lactate dehydrogenase, γ-glutamyl transferase, and n-acetyl glucosaminidase. Copper induced earlier pulmonary injury/inflammation, while zinc and nickel produced later effects. Vanadium or iron exposure induced minimal pulmonary injury/inflammation. Zinc, nickel, or copper increased serum cholesterol, red blood cells, and white blood cells at different time points. IT of nickel and copper increased expression of metallothionein-1 (MT-1) in the lung. Zinc, nickel, vanadium, and iron increased hepatic MT-1 expression. No significant changes in zinc transporter-1 (ZnT-1) expression were noted in the lung or liver; however, zinc increased cardiac ZnT-1 at 24 h, indicating a possible zinc-specific cardiac effect. Nickel exposure induced an increase in cardiac ferritin 96 h after IT. This data set demonstrating metal-specific cardiotoxicity is important in linking metal-enriched anthropogenic PM sources with adverse health effects.     

中药注射液对输液微粒的影响

目的：探讨中药注射液对输液微粒的影响。方法：利用ＺＷＦ４ＤⅡ型微粒分析仪对５％葡萄糖注射液、三种中药注射液及其与５％葡萄糖注射液的混合液中的微粒进行测量对比。结果：混合液中≥２μｍ,≥５μｍ,≥１０μｍ的微粒增加显著。结论：混合液微粒的增加是由于中药注射液带入和配伍变化产生。     

The respiratory health effects of geogenic (earth derived) PM10

Inhalation of particulate matter less than 10 µm in diameter (PM₁₀) has a range of implications for respiratory health. In order to mitigate these effects regulatory bodies have set ambient air quality guidelines based on the known dose–response relationships between PM₁₀ exposure and health outcomes. However, these data are based almost entirely on PM₁₀ from urban regions, which are typically dominated by particulates from combustion sources. In contrast, there are limited data on the respiratory health effects of particles from nonurban regions that often contain a high geogenic (earth derived) component. In this narrative review, we summarize the existing evidence for the respiratory health effects of inhalation of geogenic PM_10. We outline the impact of physicochemical properties on the lung response, with a view to identifying gaps in the field.     

Pulmonary and cardiovascular effects of traffic-related particulate matter: 4-week exposure of rats to roadside and diesel engine exhaust particles

Traffic-related particulate matter (PM) may play an important role in the development of adverse health effects, as documented extensively in acute toxicity studies. However, rather little is known about the impacts of prolonged exposure to PM. We hypothesized that long-term exposure to PM from traffic adversely affects the pulmonary and cardiovascular system through exacerbation of an inflammatory response. To examine this hypothesis, Fisher F344 rats, with a mild pulmonary inflammation at the onset of exposure, were exposed for 4 weeks, 5 days/week for 6?h a day to: (a) diluted diesel engine exhaust (PM_DEE), or: (b) near roadside PM (PM_2.5). Ultrafine particulates, which are largely present in diesel soot, may enter the systemic circulation and directly or indirectly trigger cardiovascular effects. Hence, we assessed the effects of traffic-related PM on pulmonary inflammation and activity of procoagulants, vascular function in arteries, and cytokine levels in the heart 24?h after termination of the exposures. No major adverse health effects of prolonged exposure to traffic-related PM were detected. However, some systemic effects due to PM_DEE exposure occurred including decreased numbers of white blood cells and reduced von Willebrand factor protein in the circulation. In addition, lung tissue factor activity is reduced in conjunction with reduced lung tissue thrombin generation. To what extent these alterations contribute to thrombotic effects and vascular diseases remains to be established. In conclusion, prolonged exposure to traffic-related PM in healthy animals may not be detrimental due to various biological adaptive response mechanisms.     

Health effects of carbon-containing particulate matter: focus on sources and recent research program results

Air pollution is a complex mixture of gas-, vapor-, and particulate-phase materials comprised of inorganic and organic species. Many of these components have been associated with adverse health effects in epidemiological and toxicological studies, including a broad spectrum of carbonaceous atmospheric components. This paper reviews recent literature on the health impacts of organic aerosols, with a focus on specific sources of organic material; it is not intended to be a comprehensive review of all the available literature. Specific emission sources reviewed include engine emissions, wood/biomass combustion emissions, biogenic emissions and secondary organic aerosol (SOA), resuspended road dust, tire and brake wear, and cooking emissions. In addition, recent findings from large toxicological and epidemiological research programs are reviewed in the context of organic PM, including SPHERES, NPACT, NERC, ACES, and TERESA. A review of the extant literature suggests that there are clear health impacts from emissions containing carbon-containing PM, but difficulty remains in apportioning responses to certain groupings of carbonaceous materials, such as organic and elemental carbon, condensed and gas phases, and primary and secondary material. More focused epidemiological and toxicological studies, including increased characterization of organic materials, would increase understanding of this issue.     

In vitro toxicology of ambient particulate matter: Correlation of cellular effects with particle size and components

High concentrations of airborne particulate matter (PM) have been associated with increased rates of morbidity and mortality among exposed populations. Although certain components of PM were suggested to influence these effects, no clear‐cut correlation was determined thus far. One of the possible modes of action is the induction of oxidative stress by inhaled PM triggering inflammatory responses. Therefore, the in vitro formation of reactive oxygen species (ROS) in three cell lines in the presence of five subfractions of PM₁₀, collected in Münster, Germany was investigated. The PM components chloride, nitrate, ammonium, sulfate, 68 chemical elements, and endotoxin were quantified. The highest concentration of endotoxin was found in particles of 0.42–1.2 μm aerodynamic diameters, and therefore probably subject to long‐range transport. Intracellular ROS formation in three well established mammalian cell lines (CaCo2, human; MDCK, canine; RAW264.7, mouse) only correlated positively with particle size. The two smallest PM size fractions provoked the highest rise in ROS. However, the latter did not correlate with the concentration of any PM components investigated. The smallest PM size fractions significantly dominated the number of particles. Therefore, the particle number may be most effective in inducing oxidative stress in vitro. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.     

Characteristics and popular topics of latest researches into the effects of air particulate matter on cardiovascular system by bibliometric analysis

Abstract

In recent years, many epidemiological and toxicological studies have investigated the adverse effects of air particulate matter (PM) on the cardiovascular system. However, it is difficult for the researchers to have a timely and effective overall command of the latest characteristics and popular topics in such a wide field. Different from the previous reviews, in which the research characteristics and trends are empirically concluded by experts, we try to have a comprehensive evaluation of the above topics for the first time by bibliometric analysis, a quantitative tool in information exploration. This study aims to introduce the bibliometric method into the field of PM and cardiovascular system. The articles were selected by searching PubMed/MEDLINE (from 2007 to 2012) using Medical Subject Headings (MeSH) terms “particulate matter” and “cardiovascular system”. A total of 935 eligible articles and 1895 MeSH terms were retrieved and processed by the software Thomson Data Analyzer (TDA). The bibliographic information and the MeSH terms of these articles were classified and analyzed to summarize the research characteristics. The top 200 high-frequency MeSH terms (the cumulative frequency percentage was 74.2%) were clustered for popular-topic conclusion. We summarized the characteristics of published articles, of researcher collaborations and of the contents. Ten clusters of MeSH terms are presented. Six popular topics are concluded and elaborated for reference. Our study presents an overview of the characteristics and popular topics in the field of PM and cardiovascular system in the past five years by bibliometric tools, which may provide a new perspective for future researchers.     

小容量注射液和注射用无菌粉末中不溶性微粒的测定方法研究

目的：研究用光阻法对小容量注射液和注射用无菌粉末中的不溶性微粒的测定方法。方法：分别采用全体积取样法、合并内容物直接测定法以及用适当溶剂稀释后测定法，测定每个容器中≥10μm和≥25μm的微粒数。结果：不同测定方法结果存在差异，不同仪器测定结果略有差异，大多数测试样品能符合规定，即每瓶含≥10μm的微粒数不超过6000个，含≥25μm的微粒数不超过600个。结论：制定不溶性微粒检查的品种，应在该品种项下具体指出测定方法。小容量注射液可根据样品性质分别采用合并直接测定法或用适宜溶剂稀释后测定法，注射用无菌粉末可根据样品溶解度选用合适溶剂溶解稀释后测定。     

Effects of organic chemicals derived from ambient particulate matter on lung inflammation related to lipopolysaccharide

The effects of components of ambient particulate matter (PM) on individuals with predisposing respiratory disorders are not well defined. We have previously demonstrated that airway exposure to diesel exhaust particles (DEP) or organic chemicals (OC) extracted from DEP (DEP–OC) enhances lung inflammation related to bacterial endotoxin (lipopolysaccharide, LPS). The present study aimed to examine the effects of airway exposure to OC extracted from urban PM (PM–OC) on lung inflammation related to LPS. ICR mice were divided into four experimental groups that intratracheally received vehicle, LPS (2.5 mg/kg), PM–OC (4 mg/kg), or PM–OC + LPS. Lung inflammation, lung water content, and lung expression of cytokines were evaluated 24 h after intratracheal administration. LPS challenge elicited lung inflammation evidenced by cellular profiles of bronchoalveolar lavage fluid and lung histology, which was further aggravated by the combined challenge with PM–OC. The combination with PM–OC and LPS did not significantly exaggerate LPS-elicited pulmonary edema. LPS instillation induced elevated lung expression of interleukin-1β, macrophage inflammatory protein-1α, macrophage chemoattractant protein-1, and keratinocyte chemoattractant, whereas the combined challenge with PM–OC did not influence these levels. All the results were consistent with our previous reports on DEP–OC. These results suggest that the extracted organic chemicals from PM exacerbate infectious lung inflammation. The mechanisms underlying the enhancing effects are not mediated via the enhanced local expression of proinflammatory cytokines.     

MicroRNA-365 induces apoptosis and inhibits invasion of human myeloma cells by targeting homeobox A9 (HOXA9)

The aberrant micro-RNA (miR) expression has been reported to play a vital role in proliferation and tumorigenesis and of several human cancers. MicroRNA-365 (miR-365) has been shown to exhibit tumor-suppressive or oncogenic role in several human cancers. Nonetheless, little is known about its growth regulatory role in human multiple myeloma. The present study characterized the regulatory control exercised by miR-365 in multiple myeloma. The results showed significant (P < 0.05) upregulation of miR-365 in myeloma tissues and cell lines. Overexpression of miR-365 significantly (P < 0.05) suppressed the proliferation and inhibition of miR-365 promoted the proliferation of the human myeloma cells. The tumor-suppressive effects of miR-365 were found to be the result of apoptosis in the IM-9 myeloma cells. The miR-365 overexpression also suppressed the invasion of the IM-9 myeloma cells. The homeobox gene, HOXA9 was identified as the molecular regulatory target of miR-365 in human myeloma. The overexpression of miR-365 was shown to cause suppression of HOXA9. The silencing of HOXA9 could also suppress the growth of the IM-9 myeloma cells while as the overexpression of HOXA9 could abolish the tumor-suppressive effects of miR-365. The in vivo study revealed that miR-365 inhibits the growth of the xenografted tumors. Nonetheless, the inhibition of miR-365 promotes the growth of the xenografted tumors. To sum up, the current study suggests the tumor-suppressive effects of miR-365 in human myeloma and highlights the applicability of miR-365 as vital therapeutic target against this fatal malignancy.     

Role of nuclear factor-kappa B activation in the adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture

To contribute to improving knowledge on the adverse health effects induced by particulate matter (PM) air pollution, an extensive investigation was undertaken of the underlying mechanisms of action activated by PM(2.5) air pollution collected in Dunkerque, a strongly industrialized French seaside city. Their chemical and physical characteristics have been previously determined, and earlier in vitro short-term studies have shown them to cause dose-dependent and time-dependent oxidative damage, gene expression and protein secretion of inflammatory mediators, and apoptotic events in human lung epithelial cells (L132) in culture. Hence, this work studied the activation of nuclear factor-kappa B (NF-kappaB)/inhibitory kappa B (IkappaB) by Dunkerque city PM(2.5) in these target cells, by determination of phosphorylated p65 and phosphorylated IkappaBalpha protein levels in cytoplasmic extracts, and p65 and p50 DNA binding in nuclear extracts. In PM-exposed L132 cells, there were concentration- and/or time-dependent increases in nuclear p65 and cytoplasmic IkB-alpha phosphorylation, and nuclear p65 and p50 DNA binding. Taken together, these results showed that Dunkerque city PM(2.5) were involved in the activation of the NF-kappaB/IkappaB complex, notably through the occurrence of oxidative stress conditions, and, therefore, in the gene expression and protein secretion of inflammatory mediators in target L132 cells. Hence, these findings suggested that the activation of the NF-kappaB/IkappaB complex preceded cytotoxicity in Dunkerque city PM-exposed L132 cells.     

The effect of particle size,location and season on the toxicity of urban and rural particulate matter

Abstract

Particulate matter (PM) varies in chemical composition and mass concentration based on a number of factors including location, season, source and particle size. The aim of this study was to evaluate the in vitro and in vivo toxicity of coarse and fine PM simultaneously collected at three rural and two urban sites within the metropolitan New York City (NYC) region during two seasons, and to assess how particle size and elemental composition affect toxicity. Human pulmonary microvascular endothelial (HPMEC-ST1.6R) and bronchial epithelial (BEAS-2B) cell lines were exposed to PM (50?μg/mL) and analyzed for reactive oxygen species (ROS). Mice (FVB/N) were exposed by oropharyngeal aspiration to 50?µg PM, and lavage fluid was analyzed for total protein and PMN influx. The ROS response was greater in the HPMEC-ST1.6R cell line compared to BEAS-2B cells, but the responses were significantly correlated (p?<?0.01). The ROS response was affected by location, locale and the location:size interaction in both cell lines, and an additional association for size was observed from HPMEC-ST1.6R cells. Urban fine PM generated the highest ROS response. In the mouse model, inflammation was associated with particle size and by a season:size interaction, with coarse PM producing greater PMN inflammation. This study showed that the aerodynamic size, locale (i.e. urban versus rural), and site of PM samples affected the ROS response in pulmonary endothelial and epithelial cells and the inflammatory response in mice. Importantly, these responses were dependent upon the chemical composition of the PM samples.     

Integrative analysis of mRNA and microRNA expression of a human alveolar epithelial cell(A549) exposed to water and organic‐soluble extract from particulate matter (PM)2.5

MicroRNA (miRNA) is now attracting attention as a powerful negative regulator of messenger RNA(mRNA) levels, and is implicated in the modulation of important mRNA networks involved in toxicity. In this study, we assessed the effects of particulate matter 2.5 (PM_2.5), one of the most significant air pollutants, on miRNA and target gene expression. We exposed human alveolar epithelial cell (A549) to two types of PM_2.5[water (W‐PM_2.5) and organic (O‐PM_2.5) soluble extracts] and performed miRNA microarray analysis. A total of 37 miRNAs and 62 miRNAs were altered 1.3‐fold in W‐PM_2.5 and O‐PM_2.5, respectively. Integrated analyses of miRNA and mRNA expression profiles identified negative correlations between miRNA and mRNA in both W‐PM_2.5 and O‐PM_2.5 exposure groups. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses showed that the 35 W‐PM_2.5 target genes are involved in responses to nutrients, positive regulation of biosynthetic processes, positive regulation of nucleobase, nucleoside, and nucleotide, and nucleic acid metabolic processes; while the 69 O‐PM_2.5 target genes are involved in DNA replication, cell cycle processes, the M phase, and the cell cycle check point. We suggest that these target genes may play important roles in PM_2.5‐induced respiratory toxicity by miRNA regulation. These results demonstrate an integrated miRNA‐mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 302–310, 2017.     

卡托普利对缺氧诱导的肺动脉平滑肌细胞增殖和胶原合成的抑制作用(英文)

目的:观察卡托普利(Cap)抑制缺氧诱导的肺动脉平滑肌细胞(VSMC)增殖和胶原合成的作用,方法:采用细胞计数,[~3H]脱氧胸苷,[~3H]脯氨酸掺入和细胞内游离钙测定的方法。结果:卡托普利(Cap,1μmol·L~(-1))抑制缺氧诱导的VSMC中细胞数目,[~3H]脱氧胸苷和[~3H]脯氨酸掺入及细胞内游离钙的增高,较缺氧组分别降低了25％,36％,21％和16％,硝苯吡啶也具有上述抑制作用,Bay-K-8644促进VSMC中细胞数目,[~3H]脱氧胸苷和[~3H]脯氨酸掺入及细胞内游离钙的增高,分别增加35％,55％,36％,34％,这种作用可被Cap阻断。结论:Cap抑制缺氧诱导的肺动脉平滑肌细胞增殖和胶原合成,这可能与阻断L型钙通道有关。     

茶多酚对PM2.5诱导的大鼠肺泡巨噬细胞凋亡的抑制作用

目的 研究茶多酚（tea polyphenols,TP）对SRM 2786（PM_2.5标准品）诱导的大鼠肺泡巨噬细胞（NR8383）凋亡的影响及其作用机制。方法 体外培养NR8383细胞,将其分组为对照组、模型组（125 μg·mL^–1的SRM 2786染毒组）及TP干预组（43.75,87.5,175,350 μmol·L^–1 TP+125 μg·mL^–1 SRM 2786）,分别干预24 h后,检测细胞存活率、氧化损伤（ROS和NO释放）、炎症因子释放（IL-6、IL-1β及TNF-α）、细胞凋亡率、线粒体损伤及caspase-3/caspase-9活性。结果 与对照组相比,SRM 2786可显著抑制NR8383细胞存活率,促进NO和ROS释放,促进3种炎症因子释放、线粒体损伤、细胞凋亡及caspase-3/caspase-9活性提升。而TP可显著性抑制SRM 2786诱导的NR8383细胞氧化损伤、炎性损伤、线粒体损伤,最终通过抑制caspase-3/caspase-9活性而降低细胞凋亡率,达到提高细胞存活率的目的。结论 TP可通过降低细胞氧化损伤、炎性损伤和caspase-3/caspase-9活性而抑制PM_2.5诱导的NR8383细胞线粒体途径凋亡,提高NR8383细胞活性。