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低剂量甲苯暴露后小鼠肺中神经生长因子的表达

The expression of nerve growth factor in mice lung following low-level toluene exposure.

作者信息

Fujimaki Hidekazu, Yamamoto Shoji, Nakajima Daisuke, Goto Sumio

机构信息

National Institute for Environmental Studies, Tsukuba, Ibaraki, 305-8506, Japan.

出版信息

Toxicol Lett. 2009 Dec 15;191(2-3):240-5. doi: 10.1016/j.toxlet.2009.09.004. Epub 2009 Sep 16.

DOI:10.1016/j.toxlet.2009.09.004
PMID:19765639
Abstract

To clarify the effect of indoor air pollutants on nerve growth factor (NGF) production in lung, male C3H/HeN mice were exposed to filtered air (control) or toluene at levels of 0.9 ppm, 9 ppm, or 90 ppm for 30 min via nose-only inhalation on days 0, 1, 2, 7, 14, 21, 28, 35, 42, 49 and 56. As an allergic mouse model, some mice (n=24) were immunized with ovalbumin. Lungs from each mouse were collected to determine NGF and related receptor expressions using real-time reverse transcription polymerase chain reaction (RT-PCR) analysis. NGF and TrkA mRNAs were increased in the lungs of the immunized mice following exposure to 9 ppm toluene (n=6) (P<0.05 ppm vs. 0 ppm). Remarkably increased NGF-positive bronchiolus and alveolar epithelium cells were observed in 9 ppm toluene-exposed, immunized mice. To determine NGF mediating signaling, we also examined mRNA expression of neurotrophin receptor p75 (p75(NTR)) and oxidative stress marker, heme oxygenase (HO)-1 in the lung. There is no difference in the expressions of p75(NTR) and HO-1 between toluene-exposed and control mice. The expression of CCL2 and CCL3 mRNAs was significantly elevated in 9 ppm toluene-exposed, immunized mice. These findings suggest that the exposure with volatile organic compounds enhanced NGF expression and airway inflammation stronger in allergic individuals than in healthy individuals.

摘要

为阐明室内空气污染物对肺中神经生长因子(NGF)产生的影响,在第0、1、2、7、14、21、28、35、42、49和56天,通过仅经鼻吸入的方式,将雄性C3H/HeN小鼠暴露于过滤空气(对照)或浓度为0.9 ppm、9 ppm或90 ppm的甲苯中30分钟。作为过敏性小鼠模型,部分小鼠(n = 24)用卵清蛋白进行免疫。收集每只小鼠的肺,使用实时逆转录聚合酶链反应(RT-PCR)分析来测定NGF及相关受体的表达。暴露于9 ppm甲苯的免疫小鼠(n = 6)肺中NGF和TrkA mRNA增加(P < 0.05,9 ppm vs. 0 ppm)。在暴露于9 ppm甲苯的免疫小鼠中观察到NGF阳性细支气管和肺泡上皮细胞显著增加。为确定NGF介导的信号传导,我们还检测了肺中神经营养因子受体p75(p75(NTR))和氧化应激标志物血红素加氧酶(HO)-1的mRNA表达。甲苯暴露小鼠和对照小鼠之间p75(NTR)和HO-1的表达没有差异。暴露于9 ppm甲苯的免疫小鼠中CCL2和CCL3 mRNA的表达显著升高。这些发现表明,挥发性有机化合物暴露增强了过敏个体而非健康个体的NGF表达和气道炎症。

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