邻苯二甲酸二乙基己基酯暴露对新生大鼠肺形态结构的影响

Effect of di-（2-ethylhexyl） phthalate on lung morphology of newborn rats

目的 探讨邻苯二甲酸二乙基己基酯[di-（2-ethylhexyl）phthalate,DEHP]暴露对新生鼠肺形态发育的影响. 方法 无特定病原体（specific pathogen free,SPF）级Sprague-Dawley新生大鼠105只,出生体重5.0-8.0g,共2批.第1批60只大鼠作为对照组,生后第1天起,每日腹腔注射玉米油0.2 ml.第2批45只大鼠作为暴露组,随机分为低、中和高3种剂量亚组,每组1 5只,生后第1-13天,每日腹腔注射溶有DEHP的玉米油0.2 ml,对应的DEHP剂量分别为10、100和750 mg/ （kg＆#183;d）.对照组分别于生后1、4、7和14d,暴露组于生后第14天,随机取仔鼠6只,称重后腹腔注射戊巴比妥钠35 mg/kg,取右肺中叶近胸膜处肺组织,固定包埋.光镜下观察肺组织病理改变.采用数字图像分析技术分析肺间质比例,测定肺骨架长度并计算肺骨架长度比值.采用单因素方差分析、LSD和Dunnet T3法进行统计学分析. 结果 对照组大鼠肺间质比例生后第1、4、7和14天逐渐下降,分别为（31.97±5.03）％、（30.05±3.57）％、（25.33±1.83）％和（22.01±2.19）％.其中生后第4天分别与第7天和第14天比较,以及第7天与第14天比较,差异均有统计学意义（P＜ 0.05或P＜0.01）.生后第14天时,中、高剂量亚组肺间质比例[分别为（24.11±2.78）％和（26.53±3.42）％]均高于对照组（P＜0.05或P＜0.01）.对照组肺骨架长度比值生后第1、4、7和14天逐渐增大,分别为0.047 8±0.003 7、0.050 0±0.002 9、0.071 2±0.003 0和0.084 4±0.004 3.生后第4天分别与第7天和第14天比较,以及7和14d比较,差异均有统计学意义（P＜ 0.05或P＜ 0.01）.生后14d时,低剂量亚组肺骨架长度比值与中、高剂量亚组比较,差异有统计学意义（分别为0.082 9±0.001 8、0.077 2±0.002 0和0.071 3±0.003 7,P＜ 0.05或P＜ 0.01）. 结论 中、高剂量DEHP暴露后,新生大鼠肺间质和肺泡发育受到抑制,暴露量越大,抑制作用越明显.

Objective To investigate the effect of di-（2-ethylhexyl） phthalate （DEHP） on the postnatal lung development in newborn rats.Methods A total of 60 newborn Sprague-Dawley rats （weighing 5.0-8.0 g） in five age groups were studied in the first experiment.The rats were divided based on the different postnatal ages：postnatal day （PND）I,PND4,PND7 and PND14.A total of 45 newborn Sprague-Dawley rats （weighing 5.0-8.0 g） were randomly divided into three groups according to the dosage of DEHP administered in the second experiment.The newborn rats were administered DEHP through intraperitoneal injection at 10 （low-dose subgroup）,100 （medium-dose subgroup） or 750 （high-dose subgroup） mg/kg daily from PND1 to PND13.The rats were sacrificed on PND14.Pups were sacrificed with lethal dose injection of pentobarbital sodium.The lung was removed.The right middle lobes were used for analysis.The tissue was processed for histology and lung sections were stained with HE for light microscopic （LM） morphometric measurement.The analysis was performed by means of a digital image analysis system,including pulmonary interstitial area ratio （IAR） and total length density of all segments.One-way ANOVA,LSD and Dunnet T3 methods were used for statistical analysis.Results In the normal controls,IAR decreased significantly by （31.97±5.03） %,（30.05±3.57）%,（25.33± 1.83）% and（22.01 ±2.19）%,respectively,from PND1 to PND14 （P〈0.05 or P〈0.01）.IAR in medium-and high-dose subgroups increased significantly by （24.11 ±2.78）% and （26.53± 3.42）%,respectively on PND 14.The total length density of all segments in unit area lung volume increased significantly by 0.047 8±0.003 7,0.050 0±0.002 9,0.071 2±0.003 0 and 0.084 4±0.004 3,respectively from PND1 to PND14 （P〈0.01）.In the DEHP treated animals,when compared with the control group,IAR was significantly higher on PND14 （P〈0.05 or P〈0.01）,while the total length density of all segments in unit area lung volume was significantly decreased （P〈0.05 or P〈0.01）.Length density in medium-and high-dose subgroups were higher than that of low-dose subgroup by 0.082 9±0.001 8,0.077 2±0.002 0 and 0.071 3±0.003 7,respectively on PND14 （P〈0.05 or P〈0.01）.Conclusions Medium-and high-dose DEHP affect the postnatal lung development in rats in a dose-dependent mode.