摘要目的 探讨母源性细颗粒物(particulate matter 2.5,PM2.5)暴露对仔鼠生长发育及肺功能的影响. 方法 无特定病原体级Sprague Dawley大鼠雄性25只,雌性50只,按1:2合笼.雌鼠阴道分泌物涂片检查,倒置显微镜下见雄鼠精子满视野视为妊娠第0天.将孕鼠简单随机分为对照组和PM2.5暴露组.从妊娠0～18 d分别将含5％二甲基亚砜或PM2.5抽提物混悬液(4个暴露组分别用0.1、0.5、2.5或7.5 mg/kg抽提物溶于5％二甲基亚砜)腹腔注射,每3天注射一次,待其自然分娩.观察孕鼠体重、妊娠天数、仔鼠的体重和肺组织的病理改变,计算仔鼠的肺体系数和肺组织湿重/干重比值.各组随机抽取出生后28d的仔鼠测定肺通气功能参数.采用单因素方差分析、SNK和LSD法以及非参数检验进行统计学分析. 结果 各组孕鼠和仔鼠均未出现自然死亡.2.5和7.5 mg/kg组胎窝重量均低于对照组[(65.71±9.02)、(62.55±7.64)与(69.68±11.90)朗,差异有统计学意义(F=12.205,P＜0.05).0.1、0.5、2.5组和7.5 mg/kg组的仔鼠体重分别为(5.82±0.83)、(5.76±0.49)、(5.65±0.51)和(5.36±0.64)g,其中2.5组和7.5 mg/kg组低于对照组的(5.89±0.50)g,以7.5 mg/kg组为最低(F=9.905,P＜0.05).PM2.5暴露组肺内病变分布不均一,肺泡大小不一,肺泡腔明显缩小,部分肺泡腔完全闭锁;肺泡间隔显著增厚、纤维组织增生,肺泡结构破坏,呈现肺间质纤维性病变的表现.各组肺泡数和肺泡等效表面积均小于对照组(F值分别为23.680和63.817),肺泡间隔等效厚度大于对照组(F=100.023,P＜0.05).0.5、2.5和7.5 mg/kg组肺泡数和肺泡等效表面积逐渐下降,肺泡间隔等效厚度逐渐上升,且组间差异有统计学意义(P值均＜ 0.05).2.5 mg/kg组的用力肺活量、功能残气量、0.2 s用力呼气容积、最大呼气中期流量率和静态肺顺应性低于对照组、0.1 mg/kg组和0.5 mg/kg组(P值均＜0.05),而7.5 mg/kg组功能残气量、0.2 s用力呼气容积、用力肺活量、最大呼气中期流量率和静态肺顺应性均低于对照组和其余暴露组(P值均＜ 0.05). 结论 母源性PM2.5暴露后可影响仔鼠的生长发育和改变肺形态结构,引起肺功能下降.

abstractsObjective To investigate the effect of maternal particulate matter 2.5 (PM2.5) exposure on fetal development and pulmonary function in offspring rats.Methods Seventy-five specific pathogen free Sprague Dawley rats,including 25 male and 50 female,were enrolled in the study.The rats were caged separately by 1:2 for conception.The pregnant rats were randomized into control group and PM2.5 challenge groups.Rats in PM2.5 challenge groups subjected to 5％ dimethylsulfoxide (DMSO) solution or PM2.5 resuspension at 0.1,0.5,2.5 and 7.5 mg/kg once per three days intraperitoneally till birth.Body weight of the pregnant rats,gestational days and body weight and pathological changes of pulmonary of offspring rats were investigated.Lung/body weight ratios and lung wet weight/dry weight ratios were calculated.Pulmonary function measurements of offspring rats were recorded on 28 days after birth.One-way ANOVA,SNK and LSD methods and non-parametric tests were performed for statistical analysis.Results All pregnant rats and their offsprings survived throughout the entire experiment.Tire litter weight was significantly lower in 2.5 and 7.5 mg/kg groups than that in control group [(65.71 ±9.02),(62.55 ± 7.64) vs (69.68± 11.90) g,F=12.205,P＜0.05].Body weight of offspring rats in 0.1,0.5,2.5 and 7.5 mg/kg group was (5.82±0.83),(5.76±0.49),(5.65±0.51) and (5.36± 0.64) g,respectively,showing the lowest level in 7.5 mg/kg group (F=9.905,P＜0.05),and those in 2.5 and 7.5 mg/kg group were both lower than in the control (5.89±0.50,P＜0.05).Heterogeneous pathological changes in the lungs of offspring rats were observed,together with various size of alveoli,narrowed and some completely atresic alveolar cavity in PM2.5 challenge groups.Moreover,the lung injury in this group was featured by thickened alveoli septum,proliferated fibrous tissue and destroyed alveoli,which implied pulmonary interstitial fibers lesions.There were significant less mean numbers of alveolar and alveolar interval equivalent thickness and alveolar equivalent surface area in the five PM2.5 groups compared with the control (F=23.680,100.023 and 63.817,all P＜0.05).The mean numbers of alveolar and alveolar equivalent surface area became smaller from 0.5,2.5 mg/kg group to 7.5 mg/kg group,while the alveolar interval equivalent thickness increased (all P＜0.05).Compared with the control group,0.1 and 0.5 mg/kg groups,the functional residual capacity,forced expiratory volume at 0.2 s,forced vital capacity,maximal mid-expiratory flow curve and static lung compliance were significantly lower in 2.5 mg/kg group (all P＜0.05).However,those indexes in 7.5 mg/kg group were significant lower than control and other PM2.5 groups (all P＜0.05).Conclusions Maternal PM2.5 exposure have adverse effect on fetal growth and development and pathological and structural changes in their lungs,which could reduce their pulmonary function.