Hatch Gary E, Crissman Kay, Schmid Judy, Richards Judy E, Ward William O, Schladweiler Mette C, Ledbetter Allen D, Kodavanti Urmila P
a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA and.
b Research Cores Unit , National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA.
Inhal Toxicol. 2015;27 Suppl 1:54-62. doi: 10.3109/08958378.2014.954170.
We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to O3 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH stroke-prone (SHSP), SHHF/Mcc heart failure obese (SHHF), insulin-resistant JCR:LA-cp obese (JCR) and Fawn-Hooded hypertensive (FHH)] were compared with normal strains [Wistar, Sprague-Dawley (SD) and Wistar Kyoto (WKY)]. Total glutathione (GSH + GSSG or GSx), reduced ascorbate (AH2), uric acid (UA) and antioxidant enzymes were determined in lung, heart and BALF immediately (0 h) or 20-h post 4-h nose-only exposure to 0.0, 0.25, 0.5 and 1.0 ppm O3. Basal- and O3-induced antioxidant substances in tissues varied widely among strains. Wistar rats had a robust O3-induced increase in GSx and AH2 in the lung. Two CVD strains (JCR and SHHF) had high basal levels of AH2 and GSx in BALF as well as high basal lung UA. Across all strains, high BALF GSx was only observed when high BALF AH2 was present. CVD rats tended to respond less to O3 than normal. High-basal BALF AH2 levels were associated with decreased O3 toxicity. In summary, large differences were observed between both normal and CVD rat strains in low-molecular weight antioxidant concentrations in lung, BALF and heart tissue. Wistar (normal) and JCR and SHHF (CVD) rats appeared to stand out as peculiar in terms of basal- or O3-induced changes. Results elucidate interactions among antioxidants and air pollutants that could enhance understanding of cardiopulmonary disease.
在心血管疾病和/或易患代谢综合征（CVD）的大鼠模型中，肺、心脏和支气管肺泡灌洗液（BALF）中的抗氧化物质和酶会因臭氧（O3）暴露而发生改变。将CVD品系[自发性高血压（SH）、易发生中风的SH（SHSP）、肥胖型SHHF/Mcc心力衰竭（SHHF）、胰岛素抵抗的JCR:LA-cp肥胖（JCR）和小鹿斑高血压（FHH）]与正常品系[Wistar、Sprague-Dawley（SD）和Wistar Kyoto（WKY）]进行比较。在仅经鼻暴露于0.0、0.25、0.5和1.0 ppm O3 4小时后立即（0小时）或20小时，测定肺、心脏和BALF中的总谷胱甘肽（GSH + GSSG或GSx）、还原型抗坏血酸（AH2）、尿酸（UA）和抗氧化酶。组织中的基础抗氧化物质和O3诱导的抗氧化物质在不同品系间差异很大。Wistar大鼠的肺中GSx和AH2在O3诱导下显著增加。两种CVD品系（JCR和SHHF）的BALF中AH2和GSx的基础水平较高，肺中UA的基础水平也较高。在所有品系中，仅当BALF中AH2含量高时才观察到BALF中GSx含量高。CVD大鼠对O3的反应往往比正常大鼠小。BALF中AH2的基础水平高与O3毒性降低有关。总之，在肺组织、BALF和心脏组织中，正常大鼠和CVD大鼠品系在低分子量抗氧化剂浓度方面存在很大差异。Wistar（正常）大鼠以及JCR和SHHF（CVD）大鼠在基础或O3诱导的变化方面显得尤为突出。研究结果阐明了抗氧化剂与空气污染物之间的相互作用，有助于加深对心肺疾病的理解。
