摘要
颗粒物(PM)对呼吸系统、心血管系统、神经系统和免疫系统均有损害,但目前关于吸入颗粒物对生殖损伤的研究较少。本研究旨在探讨细颗粒物(PM_(2.5))短期暴露对大鼠子宫炎症损伤及其作用机制。PM_(2.5)暴露30 d后,高剂量组大鼠的子宫脏器系数、内膜上皮细胞厚度和腺上皮高度均明显高于对照组(P<0.05),抑制剂MCC950则能明显降低PM_(2.5)对子宫的影响。子宫组织免疫荧光双染色结果显示,PM_(2.5)暴露组子宫内CD45白细胞和CD11b巨噬细胞均明显增加(P<0.05)。Elisa法检测子宫组织和血清中白介素1β(IL-1β)和转化生长因子-β1(TGF-β1),暴露组子宫组织和血清中IL-1β和TGF-β1含量明显升高(P<0.05)。Western印迹法检测结果显示,PM_(2.5)上调核苷酸结合低聚体结构域样受体3(NLRP3)、凋亡相关斑点样蛋白质(ASC)、pro-IL-1β、pro-Caspase-1和半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)的蛋白质表达量(P<0.05)。与高剂量组相比,NLRP3抑制剂MCC950能明显降低NLRP3/Caspase-1通路中关键蛋白质表达水平(P<0.05)。综上,PM_(2.5)通过激活NLRP3/Caspase-1信号,诱导大鼠子宫炎症反应,为PM_(2.5)生殖毒性预防和治疗提供理论基础。
Particulate matter(PM)can damage respiratory system,cardiovascular system,nervous system and immune system,but there are few researches on reproductive damage of particulate matter.The objectives of this study were to investigate the effect of short-term particulate matter 2.5(PM_(2.5))exposure on uterine inflammation in rats and its mechanism.After a short-term PM_(2.5)exposure,compared to control group,high dose of PM_(2.5)significantly increased the uterine-body weight ratio,endometrial epithelium thickness and gland epithelium height(P<0.05),which could be attenuated by MCC950.The numbers of CD45 leukocytes and CD11 b macrophages,and the levels of interleukin 1β(IL-1β)and transforming growth factor-β1(TGF-β1)in PM_(2.5)exposure groups were significantly increased than those in control group(P<0.05).At the same time,the protein levels of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),pro-IL-1β,pro-Caspase-1 and cysteinyl aspartate specific proteinase-1(Caspase-1)were increased after PM_(2.5)exposure.Compared to PM_(2.5)groups,MCC950 could inhibit the expression of key proteins of NLRP3/Caspase-1 signaling pathway.In conclusion,PM_(2.5)induces uterine inflammation via activating of NLRP3/Caspse-1 pathway,which would provide theoretical basis for the prevention and treatment of reproductive toxicity induced by PM_(2.5).
作者
张丰泉
赵杉
董恩恒
ZHANG Feng-Quan;ZHAO Shan;DONG En-Heng(Center for Experimental Teaching of Public Health and Preventive Medicine,School of Public Health,Xinxiang Medical University,Xinxiang 453000,Henan,China;School of Basic Medicine,Xinxiang Medical University,Xinxiang 453000,Henan,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2022年第9期1234-1241,共8页
Chinese Journal of Biochemistry and Molecular Biology
基金
河南省高校科技创新团队支持计划(No.14IRTSTHN017)资助。
关键词
细颗粒物
核苷酸结合低聚体结构域样受体3
凋亡相关斑点样蛋白质
NLRP3抑制剂MCC950
白介素1Β
转化生长因子-β1
particulate matter 2.5(PM_(2.5))
nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3(NLRP3)
apoptosis-associated speck-like protein containing a CARD(ASC)
NLRP3 inhibitors MCC950
interleukin 1β(IL-1β)
transforming growth factor-β1(TGF-β1)
