产前感染对新生大鼠肺发育的影响

目的 动态观察产前炎症暴露后新生大鼠肺形态及炎症细胞表达变化,探讨产前感染对新生大鼠肺发育影响的病理机制.方法 Wistar孕鼠按照随机数字表分为实验组和对照组,分别于孕19d和20d腹腔注射脂多糖(lipopolysaccharide,LPS)2.5mg/kg和等量生理盐水,足月自然分娩后,于日龄1d、3d、7d、14d、21 d及28 d两组分别取8只新生鼠,麻醉处死后取肺组织,以髓过氧化物酶(myeloperoxidase,MPO)和CD68作为中性粒细胞及巨噬细胞标志物,计数炎症细胞数量、图像分析测定肺泡数量、肺泡面积占组织面积比例、肺泡间隔厚度.结果 随日龄增加,新生鼠肺泡数量、肺泡占组织面积比例逐渐增加,肺泡间隔变薄,实验组炎症细胞数量逐渐减少.日龄1d、3d、7d及14d,实验组平均肺泡数量(88、89、102、127,单位:个/mm2)明显少于同日龄对照组(105、109、123和156,单位:个/mm2),P分别为0.024、0.009、0.013和0.004;日龄1d、3d和7d,实验组肺泡占组织面积比例(0.552、0.603和0.533)明显大于同日龄对照组(0.478、0.485和0.404),P分别为0.003、0.001和0.000;日龄1d及3d,实验组肺泡间隔厚度(12.30和10.75,单位:μm)明显小于同日龄对照组(17.13和16.13,单位:μm),P分别为0.000和0.000.日龄1d、3d、7d及14d,实验组中性粒细胞数量(681、582、393和379,单位:个/mm2)明显多于同日龄对照组(164、211、145和179,单位:个/mm2),P分别为0.000、0.000、0.000及0.003;日龄1d、3d及7d,实验组巨噬细胞数量(613、578和337,单位:个/mm2)明显多于同日龄对照组(170、182和127,单位:个/mm2),P分别为0.000、0.000和0.000.结论 产前炎症暴露使新生大鼠肺泡增大,数量减少,炎症细胞增多.随着新生鼠日龄的增加,肺泡发育接近正常.

The effects of prenatal infection on the lung development of rat pups

Objective To explore the effects of prenatal infection on the development of lungs by dynamic observation of morphology and numbers of inflammatory cells in lungs of rat pups exposed to antenatal inflammation.Methods Pregnant Wistar rats were randomly divided into experimental group and control group.Pregnant rats of both groups were intraperitoneal injected with either lipopolysaccharide (LPS) 2.5mg/kg or the same volume of normal saline on embryonic day 19 and 20, respectively, and were allowed to term deliver.Onday1, 3, 7, 14, 21and28 (D1, D3, D7, D14, D21 andD28), eight pups of each group were killed by 10％ chloral hydrate (1ml/kg) and lungs were collected.The numbers of myeloperoxidase (MPO) and CD68 as markers of both neutrophils and macrophages were counted.Morphometric assessments were performed by measuring the mean numbers of alveolar, the mean ratio of alveolar surface area to per tissue and the mean thickness of alveolar septum.Results With the increasing of postnatal days, the mean numbers of alveolar and the mean ratio of alveolar surface area to per tissue in both groups increased.The mean thickness of alveolar septum got thinner and the numbers of inflammatory cells decreased.On D1, D3, D7 and D14, the mean alveolar numbers of the experimental group (88, 89, 102 and 127 /mm2) were significantly less than those of the control group (105, 109, 123, 156/mm2), P =0.024, 0.009, 0.013, 0.004, respectively.On D1, D3 and D7, the mean ratios of alveolar surface area to per tissue were significantly larger (0.552,0.603 and0.533) than those of control group (0.478, 0.485 and 0.404), P=0.003, 0.001, 0.000, respectively.On D1 and D3, the alveolar septum thickness was significantly thinner (12.30 and 10.75 μm) thanthatin control group (17.13 and 16.13 μm), P=0.000, 0.000, respectively.On D1, D3, D7 and D14, the mean numbers of neutrophils of the experimental group (681, 582, 393 and 379/mm2) were significantly more than those of control group (164, 211, 145 and 179 /mm2), P =0.000, 0.000, 0.000,0.003, respectively.On D1, D3 and D7, the mean numbers of macrophages (613, 578 and 337 /mm2)were significantly more than those of control group (170, 182 and 127, /mm2) , P=0.000, 0.000, 0.000,respectively.Conclusion Prenatal infection results in larger and fewer alveolars and more inflammatory cells in lungs of rat pups.With the increasing of postnatal days, the alveolar morphology was similar to the controis.