Effects of Short-Term Cigarette Smoke Exposure on Fischer 344 Rats and on Selected Lung Proteins

Effects of Short-Term Cigarette Smoke Exposure on Fischer 344 Rats and on Selected Lung Proteins
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DOI:
10.1177/0192623310364028
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发表时间:
2010-04-01
影响因子:
1.5
通讯作者:
Misra, Manoj
Misra, Manoj
中科院分区:
医学4区
文献类型:
--
作者:
Carter, Charleata A.;Misra, Manoj

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在Fischer 344大鼠身上进行了一项为期5天的短期香烟烟雾暴露研究,以确定烟雾诱导的肺蛋白质变化。5周龄雄性和雌性大鼠各10只,随机分为4个暴露组。动物接受过滤空气(对照组)或75、200或400毫克总颗粒物(TPM)/m(3)稀释的肯塔基州参考3R4F香烟烟雾。仅鼻部暴露3小时/天,连续5天。平均体重仅在暴露于400 mg TPM/m(3)的雄性大鼠中显著降低。与对照组相比,暴露于200和400毫克TPM/m(3)的男性和所有吸烟的女性的体重增加显著减少。在所有接触烟雾的女性和暴露于200和400 mg TPM/m(3)的男性中,肺泡组织细胞增多症略有增加。环氧合酶-2染色在400 mg TPM/m(3)时增加。烟雾暴露组小鼠肺泡巨噬细胞和细支气管壁上皮细胞基质金属蛋白酶-12染色增强,尤其是400 mg TPM/m(3)暴露组。在200和400 mg TPM/m(3)剂量下,巨噬细胞的蛋白激酶C-α染色增加。烟雾暴露组织中c-jun NH2末端激酶染色减弱。已鉴定的变化的蛋白质在炎症、转化、增殖、应激激活和细胞凋亡中发挥作用。
A short-term 5-day cigarette smoke exposure study was conducted in Fischer 344 rats to identify smoke-induced lung protein changes. Groups of 10 male and 10 female rats at 5 weeks of age were randomly assigned to one of four exposure groups. Animals received filtered air (control) or 75, 200, or 400 mg total particulate matter (TPM)/m(3) of diluted Kentucky reference 3R4F cigarette smoke. Nose-only exposures were conducted for 3 hours/day for 5 consecutive days. Mean body weights were significantly reduced only in male rats exposed to 400 mg TPM/m(3). Body weight gains were significantly reduced in 200- and 400-mg TPM/m(3)-exposed males and in all smoke-exposed females compared with controls. Alveolar histiocytosis increased slightly in all smoke exposed-females and 200- and 400-mg TPM/m(3)-exposed males. Cyclooxygenase-2 staining increased at 400 mg TPM/m(3). Matrix metalloproteinase-12 staining of alveolar macrophages and bronchiolar epithelia increased in smoke-exposed animals, especially 400-mg TPM/m(3)-exposed females. Protein kinase C-alpha staining increased in macrophages at 200- and 400-mg TPM/m(3) doses. c-Jun NH2-terminal kinases staining decreased in smoke-exposed tissues. The identified changed proteins play roles in inflammation, transformation, proliferation, stress activation, and apoptosis.