Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM...Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM_(10)were collected from ambient air and given to BALB/c male mice at 0.25 mg/m^(3) concentration in whole-body inhalation chamber for 28days(6 h/day,5 days/week)to assess their effect on kidney.Physico-chemical characterization of PM particles by SEM,ICP-MS and HPLC showed their various shapes along with the presence of metals and poly aromatic hydrocarbons(PAHs).Following PM exposure,increased serum creatinine levels were observed in animals along with dilated tubules,protein cast deposition,necrosis,immune infiltration,collagen deposition,and shrunken glomeruli in kidney.Immunofluorescence staining showed higher expressions of kidney injury molecule1(KIM-1),cystatin C,β2 microglobulin(β2M),and alpha smooth muscle actin(α-SMA)and fibronectin,suggesting renal injury and fibrosis.PM exposure also increased malondialdehyde(MDA)content and decreased superoxide dismutase 2(SOD2)activity,which in turn leads to induction of inflammation.Mechanistically,PM exposure further inhibited the nuclear factor erythroid 2-related factor 2(Nrf2)signalling and induced kelch-like ECH-associated protein 1(Keap1)and nuclear factor kappa-light-chain-enhancer of activated B(NF-κB).Interestingly,the effect of PM_(2.5)was more severe than PM_(0.1)and PM_(10),leading to higher levels of proinflammatory NF-κB and greater Nrf2 inhibition.Overall,our findings suggested that inhalation exposure to size-segregated PM can cause kidney damage and fibrosis,and PM_(2.5)showed higher toxicity than PM_(0.1)and PM_(10).展开更多
目的研究不同剂量直径≤2.5μm的细颗粒物(PM2.5)诱导卵清蛋白(OVA)致哮喘小鼠肺损伤的程度。方法雄性BALB/c小鼠被随机分为正常对照组、OVA哮喘组、(1、5、15)mg/m L PM2.5处理的OVA哮喘组。收集支气管肺泡灌洗液(BALF)进行Gimsa染色...目的研究不同剂量直径≤2.5μm的细颗粒物(PM2.5)诱导卵清蛋白(OVA)致哮喘小鼠肺损伤的程度。方法雄性BALB/c小鼠被随机分为正常对照组、OVA哮喘组、(1、5、15)mg/m L PM2.5处理的OVA哮喘组。收集支气管肺泡灌洗液(BALF)进行Gimsa染色观察白细胞数量,ELISA检测小鼠血清γ干扰素(IFN-γ)、白细胞介素17(IL-17)和IL-10的含量;实时定量PCR进行外周血单个核细胞(PBMC)Toll样受体4(TLR4)、核因子κB(NF-κB)的mRNA水平;Western blot法检测T细胞表达的T盒(T-bet)、维甲酸相关孤核受体γt(RORγt)和叉头盒P3(FOXP3)蛋白水平;HE染色观察小鼠肺组织病变情况。结果与对照组相比,OVA哮喘组小鼠的肺泡间隔增厚,肺泡腔增大,且出现较明显的炎性细胞浸润,BALF中与炎症反应相关的白细胞数目增多;与OVA哮喘组相比,15 mg/m L PM2.5诱导的哮喘小鼠上述变化极其明显。与对照组相比,OVA哮喘组小鼠血清中IFN-γ、IL-10显著降低,而IL-17显著增加;与OVA哮喘组相比,15 mg/m L PM2.5处理的OVA哮喘组IFN-γ、IL-10含量显著减少,而IL-17含量显著增加。与对照组相比,OVA哮喘组小鼠PBMC中TLR4、NF-κB表达量明显增加,与OVA哮喘组相比,15 mg/m L PM2.5处理OVA哮喘组TLR4、NF-κB表达量显著增加。与对照组相比,OVA哮喘组小鼠T-bet和FOXP3蛋白水平明显降低,RORγt蛋白水平明显升高;与OVA哮喘组相比,15 mg/m L PM2.5处理OVA哮喘组小鼠T-bet和FOXP3蛋白水平极显著降低,而RORγt蛋白水平显著增加。结论 15 mg/m L PM2.5通过激活TLR4/NF-κB信号通路促进OVA诱发的哮喘和肺损伤。展开更多
基金supported by the institutional fund MLP004 and Science and Engineering Research Board(SERB)(No.CRG/2021/002625)financial assistance from DBT-JRF,Department of Biotechnology,Gov of India,New Delhi India(DBT/2018/1111)。
文摘Air pollution is fourth major cause of death worldwide.Recent evidence suggests that particulate matter(PM)may affect kidneys,and the effect may be size and composition dependent.In this study,PM_(0.1),PM_(2.5),and PM_(10)were collected from ambient air and given to BALB/c male mice at 0.25 mg/m^(3) concentration in whole-body inhalation chamber for 28days(6 h/day,5 days/week)to assess their effect on kidney.Physico-chemical characterization of PM particles by SEM,ICP-MS and HPLC showed their various shapes along with the presence of metals and poly aromatic hydrocarbons(PAHs).Following PM exposure,increased serum creatinine levels were observed in animals along with dilated tubules,protein cast deposition,necrosis,immune infiltration,collagen deposition,and shrunken glomeruli in kidney.Immunofluorescence staining showed higher expressions of kidney injury molecule1(KIM-1),cystatin C,β2 microglobulin(β2M),and alpha smooth muscle actin(α-SMA)and fibronectin,suggesting renal injury and fibrosis.PM exposure also increased malondialdehyde(MDA)content and decreased superoxide dismutase 2(SOD2)activity,which in turn leads to induction of inflammation.Mechanistically,PM exposure further inhibited the nuclear factor erythroid 2-related factor 2(Nrf2)signalling and induced kelch-like ECH-associated protein 1(Keap1)and nuclear factor kappa-light-chain-enhancer of activated B(NF-κB).Interestingly,the effect of PM_(2.5)was more severe than PM_(0.1)and PM_(10),leading to higher levels of proinflammatory NF-κB and greater Nrf2 inhibition.Overall,our findings suggested that inhalation exposure to size-segregated PM can cause kidney damage and fibrosis,and PM_(2.5)showed higher toxicity than PM_(0.1)and PM_(10).
文摘目的研究不同剂量直径≤2.5μm的细颗粒物(PM2.5)诱导卵清蛋白(OVA)致哮喘小鼠肺损伤的程度。方法雄性BALB/c小鼠被随机分为正常对照组、OVA哮喘组、(1、5、15)mg/m L PM2.5处理的OVA哮喘组。收集支气管肺泡灌洗液(BALF)进行Gimsa染色观察白细胞数量,ELISA检测小鼠血清γ干扰素(IFN-γ)、白细胞介素17(IL-17)和IL-10的含量;实时定量PCR进行外周血单个核细胞(PBMC)Toll样受体4(TLR4)、核因子κB(NF-κB)的mRNA水平;Western blot法检测T细胞表达的T盒(T-bet)、维甲酸相关孤核受体γt(RORγt)和叉头盒P3(FOXP3)蛋白水平;HE染色观察小鼠肺组织病变情况。结果与对照组相比,OVA哮喘组小鼠的肺泡间隔增厚,肺泡腔增大,且出现较明显的炎性细胞浸润,BALF中与炎症反应相关的白细胞数目增多;与OVA哮喘组相比,15 mg/m L PM2.5诱导的哮喘小鼠上述变化极其明显。与对照组相比,OVA哮喘组小鼠血清中IFN-γ、IL-10显著降低,而IL-17显著增加;与OVA哮喘组相比,15 mg/m L PM2.5处理的OVA哮喘组IFN-γ、IL-10含量显著减少,而IL-17含量显著增加。与对照组相比,OVA哮喘组小鼠PBMC中TLR4、NF-κB表达量明显增加,与OVA哮喘组相比,15 mg/m L PM2.5处理OVA哮喘组TLR4、NF-κB表达量显著增加。与对照组相比,OVA哮喘组小鼠T-bet和FOXP3蛋白水平明显降低,RORγt蛋白水平明显升高;与OVA哮喘组相比,15 mg/m L PM2.5处理OVA哮喘组小鼠T-bet和FOXP3蛋白水平极显著降低,而RORγt蛋白水平显著增加。结论 15 mg/m L PM2.5通过激活TLR4/NF-κB信号通路促进OVA诱发的哮喘和肺损伤。
