基于高通量测序分析哮喘小鼠呼吸道菌群的变化

通过高通量测序分析哮喘模型小鼠呼吸道菌群的变化情况。

将12只SPF级BALB/c雄性小鼠随机分为对照组和模型组, 每组6只。采用卵清蛋白致敏方法建立哮喘小鼠模型后, 进行支气管组织切片病理学观察, ELISA法检测血清IgE水平, 测定肺指数, 采集咽拭子后提取DNA行高通量测序分析。

与对照组比较, 模型组小鼠血清IgE水平明显升高(P < 0.05), 肺指数明显上升(P < 0.05), 可见支气管上皮粘膜有水肿, 少量淋巴细胞浸润, 平滑肌增生。模型组小鼠呼吸道菌群与对照组比较, 菌种丰度升高, 厚壁菌门较对照组减少(P < 0.05), 放线菌门和变形菌门增多(P < 0.05), 菌群结构有明显差异。

哮喘小鼠存在呼吸道微生态菌群失衡。

     

呼吸道合胞病毒下呼吸道感染与患儿鼻咽部定植菌群的关系

研究鼻咽部定植菌群与呼吸道合胞病毒（RSV）下呼吸道感染患儿病情特点的关系,从微生态角度寻找预防或治疗RSV下呼吸道感染的理论依据。

回顾性分析我院2020年8月1日到2021年10月31日收治的RSV下呼吸道感染患儿,根据鼻咽部分泌物培养结果分为阴性组、阳性组,对比两组患儿临床特点及潮气肺功能检测结果。

1 090例RSV下呼吸道感染患儿中培养阳性者290例（26.58%）,中位数年龄为8个月（3.24个月,14个月）。各年龄层患儿鼻咽部菌群定植率及定植菌群差异有统计学意义（均P＞0.05）。各年龄层患儿鼻咽部定植菌均以肺炎链球菌为主。金黄色葡萄球菌、大肠埃希菌及卡他莫拉菌定植的患儿发热率较低。与喘息相关定植菌为肺炎链球菌、流感嗜血杆菌及金黄色葡萄球菌。与重症相关的定植菌为肺炎链球菌、流感嗜血杆菌、金黄色葡萄球菌、大肠埃希菌。与大叶性肺炎发生相关的只有肺炎链球菌。肺炎链球菌及流感嗜血杆菌定植的达峰容积比（Z = −4.12,P＜0.001;Z = −1.99,P = 0.046）与达峰时间比（Z = −4.24,P＜0.001;Z = −1.98,P = 0.047）均低于阴性组。

特定鼻咽部定植菌的存在会影响RSV下呼吸道感染患儿的临床表现,同时降低婴幼儿潮气肺功能检测结果。

     

急性脑卒中患者肠道菌群研究

通过粪便标本检测急性脑卒中患者肠道菌群变化情况, 探讨急性脑卒中患者肠道菌群结构。

通过高通量二代测序技术对10例健康者(对照组)及10例急性脑卒中患者(疾病组)粪便样本进行菌群结构测序分析。

与对照组比较, 急性脑卒中患者粪便样本中物种OTU信息量显著增加(P < 0.01), 菌群多样性指数(Shannon)和物种均一度指数(Evenness)也有所增加但差异无统计学意义(均P > 0.05)。门水平上, 疾病组患者肠道Bacteroidetes数量较对照组显著增加, Firmicutes数量显著减少(均P < 0.05)。属水平上, 疾病组患者肠道Bacteroides、Bilophila、Butyricimonas比例较对照组显著升高, 而Collinsella、Coprococcus、Clostridium等比例较对照组显著降低(均P < 0.05)。

急性脑卒中患者肠道菌群结构与健康人存在显著差异。

     

呼吸窘迫综合征新生儿肠道菌群的改变

探究呼吸窘迫综合征新生儿肠道菌群的改变,为该类患儿的治疗提供参考。

选取我院2020年4月至2022年4月收治的83例呼吸窘迫综合征新生儿作为试验组,另选我院同期健康新生儿83例作为对照组,收集两组对象粪便标本。对比两组对象肠道菌群的变化情况。

与对照组相比,试验组患儿肠道菌群Chaol指数和Shannon指数显著降低,Ace指数显著升高,差异均有统计学意义（均P＜0.05）。两组对象肠道厚壁菌门、变形菌门、链球菌属相对丰度对比差异均有统计学意义（均P＜0.05）。

呼吸窘迫综合征新生儿肠道菌群改变较大。

     

夏季老年慢性阻塞性肺疾病患者口咽菌群分析

分析夏季老年慢性阻塞性肺疾病（COPD）患者与健康人群的口咽菌群构成,旨在确定老年COPD患者与健康人群上呼吸道菌群间的差异。

选择2018年6—8月沈阳市沈阳医学院附属第二医院COPD患者29例和健康体检者25例,采集口咽拭子进行细菌16S rRNA高通量测序。通过菌群多样性分析、物种组成和物种差异分析,比较老年COPD患者与健康人群口咽部微生物的异同。

老年COPD患者口咽中菌群丰富度显著高于健康人群,物种多样性低于健康人群。在门水平上,老年COPD患者口咽菌群中拟杆菌门相对丰度降低,放线菌门相对丰度显著增高;在属水平上,老年COPD患者口咽菌群中罗氏菌属、放线菌属和劳特罗普氏菌属丰度均显著高于健康人群,奈瑟菌属和普雷沃菌属相对丰度降低,差异均具有统计学意义（P＜0.05）。

老年COPD患者口咽部正常菌群组成发生变化,机会致病菌如罗氏菌属、劳特罗普氏菌属比例增加,提示夏季老年COPD患者口咽菌群失调。

     

靛蓝对葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠肠道菌群作用研究

研究靛蓝对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）模型小鼠的干预作用,并分析对小鼠肠道菌群的影响。

实验小鼠分为对照组、模型组、柳氮磺胺吡啶组（125 mg/kg）和靛蓝组（50 mg/kg),每组小鼠各9只。观察给药后小鼠体征并进行疾病活动指数（DAI）评分,通过苏木素―伊红（HE）染色观察小鼠结肠组织切片形态变化,ELISA法检测小鼠血清中IL-6、TNF-α、IL-1β、IL-8和IL-10水平;针对16S rRNA基因V4‒V5区进行高通量测序,分析小鼠肠道内容物的菌群变化。

与模型组相比,靛蓝组小鼠DAI评分降低,病理切片结果显示靛蓝可改善UC小鼠结肠黏膜损伤,减少炎性细胞浸润,血清中促炎因子IL-6、IL-8、IL-1β和TNF-α水平显著降低（t = 4.377 0、5.374 0、12.140 0、5.508 0,P = 0.011 9、0.005 8、0.000 3、0.005 3）,抑炎因子IL-10水平显著升高（t = 3.716 0,P = 0.020 5）。16S rRNA基因测序结果显示,模型组小鼠肠道菌群多样性降低,靛蓝组小鼠肠道菌群多样性升高。

给予靛蓝干预后可有效缓解UC小鼠结肠炎症状,通过降低炎症因子水平和调节UC小鼠肠道菌群平衡达到治疗UC的效果。

     

高摄入红肉通过改变肠道菌群加重小鼠溃疡性结肠炎

观察高摄入红肉对小鼠肠道菌群及溃疡性结肠炎（ulcerative colitis,UC）的影响,并探讨可能的发生机制。

40只Balb/c小鼠随机分为4组：对照组、高红肉组、DSS组和高红肉+DSS组,每组10只小鼠,对照组、DSS组小鼠给予普通饲料,高红肉组、高红肉+DSS组小鼠给予高红肉饲料,均饲养8周;此8周的最后9天开始对DSS组、高红肉+DSS组小鼠给予3% DSS诱导UC。采用实时荧光定量PCR检测小鼠肠道菌群,采用体质量变化、疾病活动指数及HE染色指标评价小鼠UC严重程度,运用Western Blot方法检测小鼠肠道巨噬细胞M1型极化的特征细胞因子。

与对照组相比,高红肉组小鼠肠道厚壁菌门、粪杆菌属及普拉梭菌的丰度显著降低,拟杆菌门、拟杆菌属的丰度显著升高。与DSS组相比,高红肉+DSS组小鼠体质量显著下降,疾病活动指数显著升高,结肠组织病理评分显著升高;与DSS组相比,高红肉+DSS组小鼠TNF-α、IL-1β及IL-6细胞因子表达显著升高。

高摄入红肉导致肠道菌群改变加重小鼠UC。

     

当归提取物对慢性湿疹小鼠相关菌群的影响

观察当归提取物对慢性湿疹的治疗作用。

将昆明小鼠采用2,4-二硝基氯苯诱导慢性湿疹模型,取30只8周龄SPF级昆明小鼠按随机数表法分为正常空白组、湿疹模型组以及当归高、中、低剂量治疗组,每组6只。空白对照组、湿疹模型组小鼠给予生理盐水,其他各治疗组小鼠给予高、中、低剂量的当归提取物灌胃。比较各组小鼠右耳肿胀程度、两耳质量、小鼠左右耳中部厚度、搔抓次数及耳组织病理学变化,采用16S高通量测序观察肠道菌群变化。

相比湿疹模型组,当归提取物能减轻湿疹小鼠耳肿胀程度（P＜0.01）;随着当归提取物浓度的增加,小鼠搔抓指数及耳厚度均显著减小（均P＜0.01）,两耳质量趋于一致,肠道厚壁菌门水平逐渐恢复且趋于空白对照组。HE染色结果显示,当归提取物治疗后小鼠耳组织表皮角化、水肿、淋巴细胞浸润及真皮血管扩张充血等病理现象均有不同程度缓解,测序结果显示慢性湿疹小鼠相关的肠道菌群随当归治疗出现一定程度的变化。

当归提取物对小鼠慢性湿疹模型具有一定的治疗作用,对相关菌群有一定的恢复作用,且可能成为慢性湿疹的主要治疗药物。

     

基于CiteSpace可视化分析生命早期肠道菌群领域研究现状和发展趋势

探讨近10年生命早期肠道菌群领域的研究现状和发展趋势,梳理知识结构,以期为今后的研究提供参考资料。

检索2012—2022年中国知网、维普、万方和Web of Science数据库中的相关文献,通过CiteSpace软件进行知识图谱的构建和可视化呈现。

2012—2022年该领域的发文量总体呈上升趋势。关键词分析表明菌群的组成与功能、菌群的发育与演化、菌群与宿主的相互作用,以及婴幼儿食品的研发生产等是现阶段研究的热点方向;16S rRNA基因测序、宏基因组测序以及代谢组学等是现在热门的研究方法。

该领域研究的重点正逐渐从菌群组成向菌群功能转变;多组学方法的整合逐渐成为新的研究趋势。

     

基于VOSviewer的肝硬化肠道微生态研究的可视化分析——

分析肝硬化肠道微生态的研究现状、热点及前沿趋势。

检索Web of Science（WOS）核心数据库建库至2020年12月31日的肝硬化肠道微生态研究的英文文章。通过文献计量分析软件VOSviewer分析发文国家、机构、作者和本研究领域的热点和前沿方向。

共检索到848篇文章。美国的Virginia Commonwealth University是肝硬化肠道微生态相关文章发表最多的机构。国外学者Bajaj JS在该领域发文量最高。肝硬化肠道微生态相关研究在《Hepatology》上的发表数量最多,为48篇。研究热点可概括为肝性脑病、代谢性肝病、菌群失衡与炎症感染等。

通过对肝硬化肠道微生态研究热点和新兴趋势进行可视化分析,为肝硬化肠道微生态的研究人员及研究单位提供了研究方向及潜在合作可能。

     

Overexpression of extracellular superoxide dismutase decreases lung injury after exposure to oil fly ash

The mechanism of tissue injury after exposure to air pollution particles is not known. The biological effect has been postulated to be mediated via an oxidative stress catalyzed by metals present in particulate matter (PM). We utilized a transgenic (Tg) mouse model that overexpresses extracellular superoxide dismutase (EC-SOD) to test the hypothesis that lung injury after exposure to PM results from an oxidative stress in the lower respiratory tract. Wild-type (Wt) and Tg mice were intratracheally instilled with either saline or 50 microg of residual oil fly ash (ROFA). Twenty-four hours later, specimens were obtained and included bronchoalveolar lavage (BAL) and lung for both homogenization and light histopathology. After ROFA exposure, EC-SOD Tg mice showed a significant reduction in BAL total cell counts (composed primarily of neutrophils) and BAL total protein compared with Wt. EC-SOD animals also demonstrated diminished concentrations of inflammatory mediators in BAL. There was no statistically significant difference in BAL lipid peroxidation; however, EC-SOD mice had lower concentrations of oxidized glutathione in the BAL. We conclude that enhanced EC-SOD expression decreased both lung inflammation and damage after exposure to ROFA. This supports a participation of oxidative stress in the inflammatory injury after PM exposure rather than reflecting a response to metals alone.     

Cigarette smoke-promoted acquisition of bacterial pathogens in the upper respiratory tract leads to enhanced inflammation in mice

Background

Bacterial colonization and recurrent infections of the respiratory tract contribute to the progression of chronic obstructive pulmonary disease (COPD). There is evidence that exacerbations of COPD are provoked by new bacterial strains acquired from the environment. Using a murine model of colonization, we examined whether chronic exposure to cigarette smoke (CS) promotes nasopharyngeal colonization with typical lung pathogens and whether colonization is linked to inflammation in the respiratory tract.

Methods

C57BL/6 N mice were chronically exposed to CS. The upper airways of mice were colonized with nontypeable Haemophilus influenzae (NTHi) or Streptococcus pneumoniae. Bacterial colonization was determined in the upper respiratory tract and lung tissue. Inflammatory cells and cytokines were determined in lavage fluids. RT-PCR was performed for inflammatory mediators.

Results

Chronic CS exposure resulted in significantly increased numbers of viable NTHi in the upper airways, whereas NTHi only marginally colonized air-exposed mice. Colonization with S. pneumoniae was enhanced in the upper respiratory tract of CS-exposed mice and was accompanied by increased translocation of S. pneumoniae into the lung. Bacterial colonization levels were associated with increased concentrations of inflammatory mediators and the number of immune cells in lavage fluids of the upper respiratory tract and the lung. Phagocytosis activity was reduced in whole blood granulocytes and monocytes of CS-exposed mice.

Conclusions

These findings demonstrate that exposure to CS impacts the ability of the host to control bacterial colonization of the upper airways, resulting in enhanced inflammation and susceptibility of the host to pathogens migrating into the lung.     

荷瘤裸鼠暴露于PM2.5后肠道菌群的急性改变

目的 研究暴露于PM2.5后的肺癌荷瘤裸鼠肠道菌群发生的急性改变。方法 18只Bac裸鼠随机分为PM2.5暴露组和对照组,每组9只。全部裸鼠应用A549细胞腋下注射后,饲养1周让其适应环境,第2周开始于动式染尘暴露仓中暴露染尘,对照组暴露于生理盐水。每天暴露2 h,每周暴露6 d,共暴露3周。利用16S rDNA分析技术对粪便标本的PCR产物进行高通量测序。结果 暴露于PM2.5的肺癌荷瘤裸鼠肠道菌群结构发生改变,与对照组荷瘤裸鼠肠道菌群相比,其厚壁菌门、拟杆菌门细菌显著减少,而致病菌变形菌门细菌增加。结论 PM2.5可以导致肺癌荷瘤裸鼠肠道菌群失衡。     

A novel inhibitory role of microRNA-224 in particulate matter 2.5-induced asthmatic mice by inhibiting TLR2

Epidemiological studies have shown that elevated concentrations of particulate matter 2.5 (PM2.5) correlate with increased incidence of asthma. Studies have highlighted the implication of microRNAs (miRNAs) in asthmatic response. Here, the objective of this study is to explore the effect of miR-224 on PM2.5-induced asthmatic mice. Ovalbumin (OVA) was utilized to establish asthmatic mouse models, which were then exposed to PM2.5, followed by miR-224 expression detection. Next, lesions and collagen deposition area in lung tissue, ratio Treg/Th17, the expression of TLR4 and MYD88, inflammation, eosinophils (EOS) and airway remodelling were evaluated in OVA mice after injection with miR-224 agomir. Following isolation of mouse primary bronchial epithelial cells, miR-224 mimic and TLR2/TLR4 inhibitor were introduced to assess inflammation and the expression of TGF-β, MMP9, TIMP-1, Foxp3, RORγt, TLR2, TLR4 and MYD88. After exposure to PM2.5, lesions and collagen deposition were promoted in lung tissues, inflammation and EOS were increased in bronchoalveolar lavage fluid (BALF), and airway remodelling was enhanced in OVA mice. miR-224 was down-regulated, whereas TLR2/TLR4/MYD88 was up-regulated in OVA mice after treatment with PM2.5, accompanied by Treg/Th17 immune imbalance. Of note, bioinformatic prediction and dual luciferase reporter gene assay confirmed that TLR2 was a target gene of miR-224. Overexpressed miR-224 reduced expression of TGF-β, MMP9, TIMP-1 and RORγt and inflammation but increased Foxp3 expression in bronchial epithelial cells through down-regulating TLR2. In summary, overexpressed miR-224 suppressed airway epithelial cell inflammation and airway remodelling in PM2.5-induced asthmatic mice through decreasing TLR2 expression.     

杭州市中心城区大气PM2.5暴露致大鼠肺部损伤作用研究

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（5 mg/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（eIF2α）,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eIF2α（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。     

Clonally related CD8+ T cells responsible for rapid population of both diffuse nasal-associated lymphoid tissue and lung after respiratory virus infection

The immune system has evolved to use sophisticated mechanisms to recruit lymphocytes to sites of pathogen exposure. Trafficking pathways are precise. For example, lymphocytes that are primed by gut pathogens can, in some cases, be imprinted with CCR9 membrane receptors, which can influence migration to the small intestine. Currently, little is known about T cell trafficking to the upper respiratory tract or the relationship between effectors that migrate to the diffuse nasal-associated lymphoid tissue (d-NALT), the lower airways, and the lung. To determine whether a T cell primed by Ag from a respiratory pathogen is imprinted for exclusive trafficking to the upper or lower respiratory tract or whether descendents from that cell have the capacity to migrate to both sites, we inoculated mice by the intranasal route with Sendai virus and conducted single-cell-sequencing analyses of CD8(+) T lymphocytes responsive to a K(b)-restricted immunodominant peptide, FAPGNYPAL (Tet(+)). Cells from the d-NALT, lung airways (bronchoalveolar lavage), lung, and mediastinal lymph node were examined 10 d postinfection to determine TCR usage and clonal relationships. We discovered that 1) Tet(+) cells were heterogeneous but preferentially used TCR elements TRAV6, TRAV16, and TRBD1; 2) both N and C termini of Vα and Vβ TCR junctions frequently encompassed charged residues, perhaps facilitating TCR αβ pairing and interactions with a neutral target peptide; and 3) T cells in the d-NALT were often clonally related to cells in the lower respiratory tract.     

Methodology for the measurement of mucociliary function in the mouse by scintigraphy.

The objective of the study was to develop a scintigraphic method for measurement of airway mucociliary clearance in small laboratory rodents such as the mouse. Previous investigations have characterized the secretory cell types present in the mouse airway, but analysis of the mucus transport system has been limited to in vitro examination of tissue explants or invasive in vivo measures of a single airway, the trachea. Three methods were used to deposit insoluble, radioisotopic colloidal particles: oropharyngeal aspiration, intratracheal instillation, and nose-only aerosol inhalation. The initial distribution of particles within the lower respiratory tract was visualized by gamma-camera, and clearance of particles was followed intermittently over 6 h and at the conclusion, 24 h postdelivery. Subsets of mice underwent lavage for evidence of tissue inflammation, and others were restudied for reproducibility of the methods. The aspiration and instillation methods of delivery led to greater distributions of deposited activity within the lungs, i.e., approximately 60--80% of the total respiratory tract radioactivity, whereas the nose-only aerosol technique attained a distribution of 32% to the lungs. However, the aerosol technique maximized the fraction of particles that cleared the airway over a 24-h period, i.e, deposited onto airway epithelial surfaces and cleared by mucociliary function such that lung retention at 24 h averaged 57% for delivery by aerosol inhalation and > or =80% for the aspiration or intratracheal instillation techniques. Particle delivery methods did not cause lung inflammation/injury with use of inflammatory cells and chemoattractant cytokines as criteria. Scintigraphy can discern particle deposition and clearance from the lower respiratory tract in the mouse, is noninvasive and reproducible, and includes the capability for restudy and lung lavage when time course or chronic treatments are being considered.     

PM2.5暴露荷瘤裸鼠后肠道菌群组成的改变

目的 了解暴露PM2.5后的Bac荷瘤裸鼠肠道菌群组成的变化。方法 采用A549细胞对30只Bac裸鼠进行肺内注射,饲养1周适应环境,第2周开始进行暴露染尘与对照暴露生理盐水组实验,共暴露1、4、8周。采用口鼻暴露仓进行小鼠染尘与生理盐水暴露操作,每周暴露6 d,每天2 h,建立大气污染暴露荷瘤裸鼠模型,5只未做处理的Bac荷瘤裸鼠作为空白对照组。采集裸鼠晨起新鲜粪便样品,抽提其中微生物总基因组DNA,采用Ⅱ代基因测序技术对粪便样品进行16S高变区扩增测序,划分可操作分类单元（operational taxonomic unit,OTU）,使用I-Sanger分析平台对所有OTU进行物种注释与评估、物种组成分析、样本比较分析等,运用R Studio软件对数据进行统计学分析。结果 厚壁菌门和拟杆菌门在PM2.5暴露组、生理盐水对照组和空白对照组均为最优势菌门。PM2.5暴露组与生理盐水对照组及空白对照组相比厚壁菌门减少,拟杆菌门增加。结论 PM2.5暴露减少Bac荷瘤裸鼠肠道菌群丰度,破坏肠道菌群平衡,在一定程度上可抑制有益菌的繁殖,并使致病菌数量增加。     

Repeated Intratracheal Instillation of PM10 Induces Lipid Reshaping in Lung Parenchyma and in Extra-Pulmonary Tissues

Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to increased hospitalization rates for cardiovascular events, typically 24 h after air pollution peaks. Particulate matter exposure is related to pulmonary and cardiovascular diseases, with increased oxidative stress and inflammatory status. Previously, we have demonstrated that repeated intratracheal instillation of PM10sum in BALB/c mice leads to respiratory tract inflammation, creating in lung a condition which could potentially evolve in a systemic toxic reaction. Additionally, plasma membrane and tissue lipids are easily affected by oxidative stress and directly correlated with inflammatory products. With this aim, in the present investigation using the same model, we analyzed the toxic potential of PM10sum exposure on lipid plasma membrane composition, lipid peroxidation and the mechanisms of cells protection in multiple organs such as lung, heart, liver and brain. Obtained results indicated that PM10 exposure led to lung lipid reshaping, in particular phospholipid and cholesterol content increases; concomitantly, the generation of oxidative stress caused lipid peroxidation. In liver we found significant changes in lipid content, mainly due to an increase of phosphatidylcholine, and in total fatty acid composition with a more pronounced level of docosahexaenoic acid; these changes were statistically correlated to lung molecular markers. Heart and brain were similarly affected; heart was significantly enriched in triglycerides in half of the PM10sum treated mice. These results demonstrated a direct involvement of PM10sum in affecting lipid metabolism and oxidative stress in peripheral tissues that might be related to the serious systemic air-pollution effects on human health.