LaGier Adriana J, Manzo Nick D, Carll Alex P, Jaskot Richard H, Slade Ralph, Richards Judy H, Winsett Darrell W, Farraj Aimen K, Dye Janice A
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Cardiovasc Toxicol. 2008 Dec;8(4):195-206. doi: 10.1007/s12012-008-9028-9. Epub 2008 Oct 25.
This study ascertains the effects of zinc, a major component of particulate matter, on pulmonary and systemic endpoints using hyperlipidemic rabbits to model diet-induced human atherosclerosis. New Zealand White rabbits were fed a normal or cholesterol-enriched diet and then were intratracheally instilled 1x/week for 4 weeks with saline or 16 microg/kg of zinc, equal parts sulfate and oxide. Physiologic responses, blood after each exposure, and terminal bronchoalveolar lavage (BAL) were assessed. Rabbits fed a cholesterol-rich diet developed hyperlipidemia and had consistently higher circulating leukocyte counts than rabbits fed normal chow. Within minutes after zinc instillation, saturation of peripheral oxygen was decreased in hyperlipidemic rabbits and heart rate was increased in hyperlipidemic rabbits with total serum cholesterol levels greater than 200 mg/dl. Total circulating leukocytes levels were increased 24 h after the first zinc instillation, but upon repeated exposures this effect was attenuated. After repeated zinc exposures, BAL fluid (BALF) N-acetylglucosaminidase activity was increased regardless of hyperlipidemic state. Hyperlipidemic rabbits had an increase in BALF-oxidized glutathione and a decrease in serum nitrite. The study elucidates mechanisms by which the zinc metal component of PM drives cardiovascular health effects, as well as the possible susceptibility induced by hyperlipidemia. Furthermore, the study exemplifies the benefits of monitoring circulatory physiology during exposure as well as after exposure.
本研究利用高脂血症兔模拟饮食诱导的人类动脉粥样硬化，以确定颗粒物的主要成分锌对肺部和全身指标的影响。给新西兰白兔喂食正常饮食或富含胆固醇的饮食，然后每周经气管内滴注1次，持续4周，分别滴注生理盐水或16微克/千克的锌（硫酸锌和氧化锌等量混合）。评估每次暴露后的生理反应、血液情况以及终末支气管肺泡灌洗（BAL）结果。喂食富含胆固醇饮食的兔子出现了高脂血症，其循环白细胞计数始终高于喂食正常食物的兔子。在滴注锌后的几分钟内，高脂血症兔子的外周血氧饱和度降低，血清总胆固醇水平大于200毫克/分升的高脂血症兔子心率增加。首次滴注锌24小时后，循环白细胞总数增加，但反复暴露后这种效应减弱。反复暴露于锌后，无论高脂血症状态如何，支气管肺泡灌洗液（BALF）中的N - 乙酰氨基葡萄糖苷酶活性均增加。高脂血症兔子的BALF中氧化型谷胱甘肽增加，血清亚硝酸盐减少。该研究阐明了颗粒物中的锌金属成分影响心血管健康的机制，以及高脂血症可能导致的易感性。此外，该研究还例证了在暴露期间以及暴露后监测循环生理指标的益处。
