Tracheal Morphologic and Protein Alterations Following Short-Term Cigarette Mainstream Smoke Exposure to Rats
Tracheal Morphologic and Protein Alterations Following Short-Term Cigarette Mainstream Smoke Exposure to Rats
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DOI：
10.1293/tox.25.201
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发表时间：
2012-09-01
影响因子：
1.2
通讯作者：
Maronpot, Robert R.
中科院分区：
文献类型：
--
作者：
Carter, Charleata A.;Misra, Manoj;Maronpot, Robert R.
在Fisher 344大鼠中进行了为期5天的短期仅鼻香烟烟雾暴露研究，以确定烟雾诱导的气管蛋白质变化。将每组10只5周龄雄性和雌性大鼠分配至4个暴露组之一。动物接受过滤空气或75、200或400 mg总颗粒物（TPM）/m3稀释的3R 4F肯塔基州参考香烟主流烟雾。暴露进行3小时/天，连续5天。一半大鼠的气管被处理用于病理学，另一半大鼠的气管立即冷冻用于蛋白质组学。我们假设，烟雾会激活气管炎症，凋亡，增殖和应激诱导的途径。烟雾暴露动物的纤毛缩短和气管粘膜上皮损失证明了吸入材料的粘膜上皮毒性。所有烟雾暴露组均出现粘膜变薄，200和400 mg TPM/m3组出现增生性修复反应。使用基于抗体的微阵列技术筛选来自对照与处理动物的气管裂解物的800种蛋白质，随后通过Western印迹评估变化最大的蛋白质。气管蛋白质表达水平高，显着增加或减少烟雾暴露依赖于密切和性别，包括caspase 5，ERK 1/2和p38。形态学和蛋白质变化之间共同的信号通路是应激、凋亡、细胞周期控制、细胞增殖和存活。受烟雾暴露影响的已鉴定蛋白质的变化与气管粘膜病理学相关，可能诱导功能性气管变化，并可作为气管损伤和相关疾病的早期指标。(DOI：10.1293/tox.25.201; J Toxicol Pathol 2012; 25：201-207）
A short-term 5-day nose-only cigarette smoke exposure study was conducted in Fisher 344 rats to identify smoke-induced tracheal protein changes. Groups of 10 male and female 5 week old rats were assigned to 1 of 4 exposure groups. Animals received filtered air, or 75, 200 or 400 mg total particulate matter (TPM)/m(3) of diluted 3R4F Kentucky reference cigarette mainstream smoke. Exposures were conducted for 3 hrs/day, for 5 consecutive days. Tracheas from half the rats were processed for pathology, and tracheas from the other half of the rats frozen immediately for proteomics. We hypothesized that smoke will activate tracheal inflammatory, apoptotic, proliferative, and stress-induced pathways. Mucosal epithelial toxicity from the inhaled material was evidenced by cilia shortening and loss of tracheal mucosal epithelium in smoke-exposed animals. Mucosal thinning occurred in all smoke-exposed groups with hyperplastic reparative responses in the 200 and 400 mg TPM/m(3) groups. Tracheal lysates from control vs. treated animals were screened for 800 proteins using antibody-based microarray technology and subsequently the most changed proteins evaluated by Western blot. Tracheal proteins expressed at high levels that were markedly increased or decreased by smoke exposure depended on close and gender and included caspase 5, ER K 1/2 and p38. Signaling pathways common between the morphologic and protein changes were stress, apoptosis, cell cycle control, cell proliferation and survival. Changes in identified proteins affected by smoke exposure were associated with tracheal mucosal pathology, may induce functional tracheal changes, and could serve as early indicators of tracheal damage and associated disease. (DOI: 10.1293/tox.25.201; J Toxicol Pathol 2012; 25: 201-207)