Paquette N C, Zhang L Y, Ellis W A, Scott A L, Kleeberger S R
Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
Am J Physiol. 1996 Mar;270(3 Pt 1):L475-82. doi: 10.1152/ajplung.1996.270.3.L475.
The present study determined the effects of vitamin A (vA) deficiency on the responses to ozone (O3) challenges in two inbred strains of mice that are differentially susceptible to O3-induced lung inflammation. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) dams at 2 wk gestation were fed test diets containing either 0 or 10 micrograms retinol/g diet. In mice that were maintained on vA-sufficient (vA+) diet, lung and liver tissue concentrations of vA and retinyl palmitate (RP) were significantly (P<0.05) lower in the B6 strain compared with C3, as measured by high-performance liquid chromatography techniques. vA and RP levels were significantly (P<0.05) reduced in lung and liver tissues of 8-wk old B6 and C3 mice that were maintained on a vA deficient (vA-) diet. vA+ and vA- mice of both strains were exposed to air or 0.3 ppm O3/72 h, and lung injury was assessed by differential cell count and total protein concentration in bronchoalveolar lavage (BAL) returns. O3 exposure caused significantly (P<0.05) greater increases in inflammatory cells and a total protein in BAL returns of vA+ B6 mice than vA+ C3 mice. vA deficiency significantly (P<0.05) enhanced O3-induced increases in polymorphonuclear leukocytes in C3 mice and epithelial cells loss in both strains. Compared with vA+ mice, lung permeability was also significantly (P<0.05) enhanced in vA- mice of both strains exposed to O3. vA replacement partially reversed the O3-induced lung injury that was enhanced by vA- diet. Results indicate that vA may have an important role in the pathogenesis of O3-induced lung injury in differentially susceptible inbred strains of mice.
本研究确定了维生素A（vA）缺乏对两种对臭氧（O3）诱导的肺部炎症敏感性不同的近交系小鼠对O3挑战的反应的影响。妊娠2周的易感C57BL/6J（B6）和抗性C3H/HeJ（C3）母鼠喂食含0或10微克视黄醇/克饮食的试验日粮。通过高效液相色谱技术测定，在喂食vA充足（vA+）日粮的小鼠中，B6品系的肺和肝组织中vA和视黄醇棕榈酸酯（RP）的浓度显著（P<0.05）低于C3品系。在喂食vA缺乏（vA-）日粮的8周龄B6和C3小鼠的肺和肝组织中，vA和RP水平显著（P<0.05）降低。两个品系的vA+和vA-小鼠暴露于空气或0.3 ppm O3/72小时，并通过支气管肺泡灌洗（BAL）回收液中的细胞分类计数和总蛋白浓度评估肺损伤。与vA+ C3小鼠相比，O3暴露导致vA+ B6小鼠BAL回收液中的炎症细胞和总蛋白显著（P<0.05）增加。vA缺乏显著（P<0.05）增强了C3小鼠中O3诱导的多形核白细胞增加以及两个品系中的上皮细胞损失。与vA+小鼠相比，暴露于O3的两个品系的vA-小鼠的肺通透性也显著（P<0.05）增强。vA补充部分逆转了由vA-日粮增强的O3诱导的肺损伤。结果表明，vA可能在对O3诱导的肺损伤敏感性不同的近交系小鼠的发病机制中起重要作用。
