PM2.5鼻腔滴注致小鼠海马组织损伤的炎性机制

doi:10.12047/j.cjap.5916.2020.053

中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (3): 240-244.doi: 10.12047/j.cjap.5916.2020.053

PM_2.5鼻腔滴注致小鼠海马组织损伤的炎性机制

方振^{1, 2}, 胡西厚¹, 李康², 韩洁^{2, 3}, 田蕾², 闫峻², 张伟², 来文庆², 林本成², 刘晓华^{2, 3△}, 袭著革^{1, 2△}

1. 滨州医学院公共卫生与管理学院, 山东烟台 264000;
2. 军事科学院军事医学研究院环境医学与作业医学研究所, 天津 300050;
3. 天津体育学院, 天津 301617

收稿日期:2019-07-29 修回日期:2020-05-12 发布日期:2020-09-25
通讯作者: Tel: 13116140682,13682117760; E-mail: liuxiaohua1992@sina.com,zhugexi2003@sina.com
基金资助:
国家重点研发计划项目(2017YFC0702700);军队项目(AWS16J004,BWS17J025)

Inflammatory mechanism of hippocampal tissue injury induced by PM_2.5 in nasal drip in mice

FANG Zhen^1,2, HU Xi-hou¹, LI Kang², HAN Jie^2,3, TIAN Lei², YAN Jun², ZHANG Wei², LAI Wen-qing², LIN Ben-cheng², LIU Xiao-hua^2,3△, XI Zhu-ge^1,2△

1. School of Public Health and Management, Binzhou Medical College, Yantai 264000;
2. Institute of Environmental and Operational Medicine of Academy of Military Medical Sciences of Academy of Military Sciences, Tianjin 300050;
3. Tianjin University of Sport, Tianjin 301617, China

Received:2019-07-29 Revised:2020-05-12 Published:2020-09-25

摘要/Abstract

摘要： 目的: 探讨鼻腔滴注不同浓度的PM_2.5对小鼠海马组织损伤的炎性机制。方法: 30只C57BL/6J小鼠随机分为3组(n=10):对照组、低剂量组、高剂量组。采用鼻腔滴注方法进行染毒,每次染毒前测量体重,低剂量组和高剂量组PM_2.5染毒剂量分别为1.5 mg/kg BW和7.5 mg/kg BW,对照组给予等体积的生理盐水,隔天染毒一次,共12次。用ELISA法测定血清中肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)水平。HE染色和电镜观察肺和海马组织的病理变化及超微结构。用抗体芯片技术测定海马组织炎性细胞因子水平。结果: PM_2.5鼻腔滴注染毒对小鼠血清中TNF-α、IL-1β和IL-6水平无显著影响(P＞0.05),肺组织结构也无明显病理改变。而在海马组织中,低剂量和高剂量PM_2.5暴露均能导致海马CA3区神经元排列紊乱,并存在神经元细胞周围突触数量减少,小血管周围水肿等超微结构变化。利用抗体芯片检测海马组织炎性细胞因子表达变化,结果显示,与对照组比较,低剂量组海马组织中CX3CL1、CSF2和TECK等炎性细胞因子水平显著升高(P＜0.05),而MIG和sTNFR1显著降低(P＜0.05);高剂量组中炎性因子CX3CL1、CSF2和TCA-3等显著升高(P＜0.05),而Leptin、MIG和FASLG等显著降低(P＜0.05)。结论: PM_2.5鼻腔滴注可诱导小鼠海马组织结构损伤,其作用途径可能为嗅脑通路,引起海马损伤的炎性机制可能与TNF-α和IL-6等促炎因子的显著升高和sTNFR1 、FASLG等炎性疾病标志物的显著降低有关。

关键词: PM_2.5, 海马, 抗体芯片, 炎性因子, 嗅脑通路:小鼠

Abstract: Objective: To investigate the inflammatory mechanism of nasal instillation of fine particulate matter (PM_2.5)on hippocampal tissue injury in mice.Methods: Thirty C57BL/6J mice were randomly divided into 3 groups(n=10):control group, low-dose group, high-dose group. The nasal instillation doses of PM_2.5 in the low-dose group and the high-dose group were 1.5 mg/kg BW and 7.5 mg/kg BW, respectively, and the control group was given saline with an equal volume. Saline was sprayed once every other time for 12 times. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were determined by ELISA method. HE staining and electron microscopy were used to observe the pathological changes and ultrastructure of lung tissue and hippocampus. The inflammatory cytokine levels in hippocampus were detected by antibody chip technique. Results: There was no significant effect of PM_2.5nasal instillation on serum TNF-α, IL-1β and IL-6 levels (P＞0.05), and there was no obvious pathological changes in lung tissue structure. In hippocampus, low-dose and high-dose PM_2.5 exposure could lead to disordered neuronal arrangement in the hippocampal CA3 region, and there were neurological changes around the neuron cells and ultrastructural changes such as edema around small blood vessels. Compared with the control group, the levels of inflammatory cytokines such as CX3CL1, CSF2 and TECK in the low-dose group were increased significantly (P ＜0.05), while sTNFR1 was decreased significantly (P＜0.05); the inflammatory factors CX3CL1, CSF2, and TCA-3 were significantly increased in the high-dose group (P＜0.05), while leptin, MIG, and FASLG were significantly decreased (P＜0.05). Conclusion: Nasal instillation of PM_2.5 can induce tissue damage in the hippocampus of mice, and its mechanism of action may be the olfactory brain pathway. The increasing of TNF-α and IL-6 and the decreasing of sTNFR1 and FASLG may be involved in inflammatory mechanisms.

Key words: PM_2.5, hippocampus, antibody chip, inflammatory factor, olfactory pathway, mice

中图分类号:

R122

方振, 胡西厚, 李康, 韩洁, 田蕾, 闫峻, 张伟, 来文庆, 林本成, 刘晓华, 袭著革. PM_2.5鼻腔滴注致小鼠海马组织损伤的炎性机制[J]. 中国应用生理学杂志, 2020, 36(3): 240-244.

FANG Zhen, HU Xi-hou, LI Kang, HAN Jie, TIAN Lei, YAN Jun, ZHANG Wei, LAI Wen-qing, LIN Ben-cheng, LIU Xiao-hua, XI Zhu-ge. Inflammatory mechanism of hippocampal tissue injury induced by PM_2.5 in nasal drip in mice[J]. CJAP, 2020, 36(3): 240-244.

参考文献

[1] 陈熙勐, 张皓旻, 顾万清, 等. 我国 PM_2.5 主要成分及对人体健康危害研究进展[J]. 中华保健医学杂志, 2019, 26(1): 83-85.
[2] 齐爱, 张亚娟, 杨惠芳, 等. 大气 PM_2.5 对心血管系统影响及其作用机制研究进展[J]. 环境与健康, 2016, 33(5): 465-469.
[3] Fu PF, Guo XB, Cheung FMH, et al. The association between PM_2.5 exposure and neurological disorders: A systematic review and meta-analysis[J]. Sci Total Environ, 2019, 655: 1240-1248.
[4] 毛旭, 史纯珍. 小鼠肺组织染毒方法的研究进展[J]. 环境与健康, 2017, 34(8): 745-747.
[5] Li K, Li L, Cui B, et al. Early postnatal exposure to airborne fine particulate matter induces autism-like phenotypes in male rats[J]. Toxicol sci, 2018, 162(1): 189-199.
[6] Liu XD, Zhang YC, Yang X. PM_2.5 induced neurodegenerative-like changes in mice and the antagonistic effects of vitamin E[J]. Toxicol Res, 2019, 8(2): 172-179.
[7] Shou YK, Huang YL, Zhu XZ,et al. A review of the possible associations between ambient PM_2.5 exposures and the development of Alzheimer's disease[J]. Ecotoxicol Environ Saf, 2019, 174: 344-352.
[8] Hedges DW, Erickson LD, Kunzelman J, et al.Association between exposure to air pollution and hippocampal volume in adults in the UK Biobank[J]. Neurotoxicology, 2019, 74: 108-120.
[9] Wei HY, Feng Y, Liang F, et al. Role of oxidative stress and DNA hydroxymethylation in the neurotoxicity of fine particulate matter[J]. Toxicology, 2017, 380: 94-103.
[10]田程远, 严明, 张云, 等. 杭州市中心城区大气PM_2.5暴露致大鼠肺部损伤作用研究[J]. 中国应用生理杂志, 2018, 34(4): 299-303.
[11]罗斌, 王丽娜, 晚亚雄. 低温条件下大气PM_2.5对大鼠心脏抗氧化能力及炎症反应的影响[J]. 环境与健康, 2015, 31(1): 11-13.
[12]Rasmussen R, Bache S, Stavngaard T, et al. Plasma levels of IL-6, IL-8, IL-10, ICAM-1, VCAM-1, IFN-γ and TNF-α are not associated to delayed cerebral ischemia, cerebral vasospasm or clinical outcome in patients with subarachnoid hemorrhage[J]. World Neurosurg, 2019,102(5): 1131-1136.
[13]王洁洁, 徐家丽. 粒细胞集落刺激因子的神经保护作用机制[J]. 临床儿科杂志, 2011, 29(4): 389-392.
[14]Lauro C, Catalano M, Trette F, et al. Fractalkine in the nervous system: neuroprotective or neurotoxic molecule[J]. Ann N Y Acad Sci, 2015, 1351: 141-148.
[15]陈然, 管晨, 孙益. Fractalkine的神经保护作用[J]. 中国病理生理杂志, 2008, 24(12): 2484-2487.
[16]Al-dwairi A, Alqudah M, Al-shboul O, et al. Metformin exerts antiinflam matory effects on mouse colon smooth muscle cells in vitro[J]. Exp Ther Med, 2018, 16: 985-992.
[17]施栋梁, 林青. 趋化因子CXCL9、CXCL10、CXCL11与狼疮肾炎相关性研究进展[J]. 免疫学杂志, 2016, 32(7): 630-633.
[18]Lianga HY, Dinga XF, Yu YW, et al. Adipose-derived mesenchymal stem cells ameliorate acute liver injury in rat model of CLP induced-sepsis via sTNFR1[J]. Exp Cell Res, 2019, 12(1): 1-7.
[19]陈泽南, 蒿艳蓉, 林辉. CCR9/ CCL25 在非小细胞肺癌中的作用机制及预后分析的研究进展[J]. 临床与实验病理学杂志, 2019, 35(4): 440-442.
[20]齐姣, 竺向佳, 卢奕, 等. MCP-1与眼部单核细胞浸润性疾病[J]. 国际眼科纵览, 2018, 42(5): 307-311.
[21]洪杨, 尚超, 薛一雪, 等. 人脑胶质瘤中miR-21调控FASLG基因表达的作用及机制[J]. 解剖科学进展, 2015, 21(3): 320-323.
[22]朱慧, 董睿清, 刘浩, 等. MSC介导CD30L等4种炎症相关因子在治疗 DMD中发挥作用[J]. 延安大学学报, 2018, 16(3): 7-12.
[23]杨东英. Leptin基因的研究进展[J]. 中国牛业科学, 2013, 39(6): 45-48.

PM_2.5鼻腔滴注致小鼠海马组织损伤的炎性机制

Inflammatory mechanism of hippocampal tissue injury induced by PM_2.5 in nasal drip in mice

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PM2.5鼻腔滴注致小鼠海马组织损伤的炎性机制

Inflammatory mechanism of hippocampal tissue injury induced by PM2.5 in nasal drip in mice

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PM_2.5鼻腔滴注致小鼠海马组织损伤的炎性机制

Inflammatory mechanism of hippocampal tissue injury induced by PM_2.5 in nasal drip in mice