高氧致慢性肺疾病新生鼠肺泡上皮细胞AQP_1和AQP_5表达及其意义

目的探讨高氧损伤状态下,肺组织内水通道蛋白1(AQP1)和AQP5 mRNA的动态变化规律及其在肺水肿中的作用。方法新生鼠320只,依据吸氧浓度(FiO2)分组:实验组1(FiO20.8)、实验组2(FiO20.6)、实验组3(FiO20.4)、空气对照组(FiO20.21)。每组分别于实验后1、3、5、7、14d行AQP1 mRNA、AQP5 mRNA RT-PCR检测,同时检测肺组织Evans蓝含量。结果高氧各组肺组织Evans蓝含量与空气组相比均显著增加,并随吸氧浓度、暴露时间的延长而增加。新生大鼠肺组织AQP1(高氧3d时)、AQP5(高氧5d时)基因表达明显低于对照组(F1=53.004,P=0.008;F2=16.617,P=0.01),总趋势上AQP1、AQP5 mRNA的表达实验组1、实验组2、实验组3依次降低。结论AQP1、AQP5 mRNA在高氧肺损伤时表达降低,并与肺水肿的严重程度密切相关。     

水通道蛋白-1,-5与新生鼠高氧肺损伤肺水肿的关系研究

目的：水通道蛋白(aquaporin,AQP)是新近发现的一组与水通透性有关的细胞膜转运蛋白,该文旨在探讨高氧损伤状态下,肺组织内AQP1,AQP5的动态变化规律及其在肺水肿中的作用。方法：新生鼠200只,依据吸氧浓度(F iO2)分组:实验组1(F iO2=0.8)、实验组2(F iO2=0.6)、实验组3(F iO2=0.4)、空气对照组(F iO2=0.21)。每组分别于实验后1,3,5,7,14 d行AQP1、AQP5W estern印迹检测,同时检测肺湿/干重比值(wet/dry we ight ratio,W/D),BALF中蛋白含量。结果：高氧各组肺W/D比值、BALF中蛋白含量与空气组相比均显著增加,并随吸氧浓度、暴露时间的增加而增加。实验组AQP1第3天表达开始降低,第5天,第7天明显降低(P<0.05),第14天有所恢复。实验组AQP5表达低于对照组,第1,3天呈稍高表达,以后随日龄增加逐渐降低(P<0.05)。总趋势上AQP1,AQP5的表达在实验组3、实验组2、实验组1依次降低。结论：AQP1,AQP5在高氧肺损伤时表达降低,并与肺水肿的严重程度相关。     

高氧致新生鼠慢性肺疾病HoxB5 SPC AQP5表达及其意义

目的：肺泡上皮损伤是慢性肺疾病（CLD）主要病理改变之一,HoxB5基因是在肺发育过程中表达强烈的基因之一。该文探讨高浓度氧致新生鼠肺损伤时肺泡上皮损伤及修复能力,研究HoxB5在这一损伤中的动态表达规律及其与前者的关系。方法：建立高氧诱导新生鼠CLD模型, 80只早产鼠被随机分为实验组及对照组,分别应用免疫组化及RT-PCR技术测定肺组织HoxB5,SPC,AQP5蛋白及mRNA表达。结果：实验组肺组织HoxB5表达7 d后逐渐减少;高氧肺损伤SPC 3 d表达明显减少,7 d后开始增多,14 d、21 d明显高于对照组;而AQP5随着肺损伤加重表达量进行性下降。结论：高氧肺损伤新生鼠肺泡上皮细胞损伤明显,根据SPC,AQP5表达结果提示I型肺泡上皮细胞（AECI）损伤更甚且未得到正常修复,II型肺泡上皮细胞（AECII）虽然数量有所增加但其分化转化能力明显下降,而 HoxB5表达量减少可能致使大量的AECII失去了分化为AECI的功能。［中国当代儿科杂志,2009,11（1）：51-55］     

高体积分数氧致慢性肺疾病新生鼠信号转导转录活化因子3表达及其对表面活性蛋白-B的影响

目的 探讨高体积分数氧(高氧)损伤状态下,肺组织内信号转导转录活化因子3(STAT3)的动态变化规律,及其对表面活性蛋白-B(SP-B)的影响.方法 新生鼠160只,依据吸氧体积分数(FiO2)分为4组:实验1组(FiO2=800 mL·L-1)、实验2组(FiO2=600 mL·L-1)、实验3组(FiO2=400 mL·L-1)、空气对照组(FiO2=210 mL·L-1).每组分别于实验1 d、3 d、5 d、7 d、14 d,免疫组织化学检测STAT3水平,反转录-PCR检测SP-B水平.结果 高氧暴露使SP-B mRNA表达异常,实验1组1 d、3 d SP-B mRNA 水平与空气对照组比较差异均无统计学意义(Pa>0.05),实验1组5 d、7 d、14 d SP-B mRNA水平与空气对照组比较差异均有统计学意义(Pa<0.05),实验2组5 d时SP-B mRNA水平与空气对照组比较差异有统计学意义(P<0.05),实验3组与空气对照组差异无统计学意义(P>0.05).实验各组肺组织STAT3蛋白的表达高氧刺激3 d明显增加,5 d、7 d差异更为显著(Pa<0.05).实验组SP-B mRNA表达与STAT3呈明显正相关(r=0.892,P<0.001).结论 高氧肺损伤的早期伴随有信号转导酪氨酸蛋白激酶STAT3通路的激活发挥其对肺组织的保护作用,SP-B合成、分泌信号可能是STAT3途径转导的.     

基质金属蛋白酶-8及其组织抑制因子-1在高氧致新生鼠肺纤维化中的基因表达及其意义

目的：近年来研究发现细胞外基质（ECM）的过度沉积与肺纤维化发生密切相关，而ECM合成与降解在新生儿慢性肺疾病的肺纤维化发生、发展中作用如何尚不清楚。本文着重研究基质金属蛋白酶-8（MMP-8, Ⅰ型胶原的降解酶）及其组织抑制因子-1（TIMP-1）基因在高氧致新生鼠肺损伤中的表达，并探讨其在纤维化中的作用。方法：80只足月新生大鼠依吸氧浓度（FiO2）随机分为高氧组（FiO2＝0.90）和对照组（FiO2＝0.21）,每组均为40只。采用高浓度氧诱导新生鼠肺损伤模型，应用酶联免疫吸附法（ELISA）、免疫组织化学及反转录聚合酶链反应（RT-PCR）技术，动态研究MMP-8及TIMP-1 mRNA表达，并同时观察肺组织Ⅰ型胶原蛋白的表达强度及其含量变化。结果：实验后14 d 和21 d的高氧组肺组织中，Ⅰ型胶原蛋白表达和Ⅰ型胶原水平均高于对照组， 差异有显著性意义。 而实验后14 d 和21 d，高氧组肺组织MMP-8 mRNA表达降低，TIMP-1 mRNA表达增高，与对照组比较差异有显著性意义。结论：高氧通过下调MMP-8及上调TIMP-1基因表达，导致ECM降解减少，过量ECM沉积于肺组织, 这可能是高氧致肺纤维化的机制之一。［中国当代儿科杂志，2007，9（1）：1-5］     

高体积分数氧致慢性肺疾病新生鼠肺泡II型上皮细胞超微结构的改变

目的 探讨高体积分数氧(高氧)损伤状态下,新生鼠肺组织通透性及肺泡Ⅱ型上皮细胞(AECⅡ)超微结构的动态变化.方法 新生大鼠320只,依据吸氧体积分数(FiO2)分组:实验组1(FiO2 800 mL·L-1)、实验组2(FiO2 600 mL·L-1)、实验组3(FiO2 400 mL·L-1)、空气对照组(FiO2 210 mL·L-1).每组分别于实验1 d、3 d、5 d、7 d、14 d取 8只鼠,计算其肺湿/干质量比值(W/D);另取8只新生鼠行支气管肺泡灌洗,检测其支气管肺泡灌洗液(BALF)中蛋白水平的动态变化; 透射电镜及硝酸镧示踪技术观察其AECⅡ超微结构及细胞膜通透性改变.结果 各实验组5 d、7 d、14 d肺W/D比值明显高于空气对照组,差异均有统计学意义(Pa<0.05),高氧3 d后实验组1与实验组2、实验组3的BALF中蛋白水平与空气对照组比较均显著增高(Pa<0.05);各实验组 7 d 内随暴露时间延长呈上升趋势;BALF 中蛋白水平在实验组3、实验组2、实验组1也呈逐渐增高趋势,且与空气对照组比较均显著增高(Pa<0.05).实验组AECⅡ的超微结构在出生后不同时间可以出现明显改变,且对硝酸镧颗粒通透性明显增加.结论 高氧肺损伤早期存在肺泡上皮通透性增加导致的肺水肿改变;新生鼠随着高氧暴露浓度的增高和时间的延长,肺损伤加重.     

高体积分数氧致慢性肺疾病新生大鼠肺组织血小板源性生长因子的动态表达

目的 探讨高体积分数氧(高氧)损伤状态下,新生大鼠肺组织内血小板源性生长因子(PDGF)的动态变化.方法 新生Wistar大鼠320只.依据吸氧体积分数(FiO2)分为实验1组(FiO2=800 mL·L-1)、实验2组(FiO2=600 mL·L-1)、实验3组(FiO2=400 mL·L-1)及空气对照组(FiO2=210 mL·L-1).实验第1、3、5、7、14天,无菌取其肺组织,采用免疫组织化学法检测各组肺组织PDGF-A、PDGF-B、PDGF受体(PDGFR)-α、PDGFR-β的表达,MetaMorph软件测定平均光密度值,以表示肺组织PDGF-A、PDGF-B、PDGFR-α、PDGFR-β蛋白的表达水平.应用SPSS 11.5软件进行统计学分析.结果实验1组及实验2组第1天肺组织PDGF-B表达均低于空气对照组(Pa<0.05 );实验1组第5、7天,实验2组及实验3组第7天肺组织PDGF-B表达均高于空气对照组(Pa<0 05 ).PDGFR-β高氧刺激后持续增高,3个实验组第1天、第3天时与空气对照组比较无显著差异,第5、7、14天均明显高于空气对照组(Pa＜0.05).3个实验组PDGF-A 、PDGFR-α与空气对照组比较差异无统计学意义.结论 吸入高氧使新生大鼠肺组织PDGF-B、PDGFR-β表达增加,是导致早期高氧肺损伤可能途径之一.     

不同吸氧浓度和时间在新生小鼠视网膜病发病中的作用

目的评价不同吸氧浓度（fraction of inhaled oxygen,FiO2）及吸氧时间在新生小鼠视网膜病中的致病作用。方法选择7日龄（P7）新生C57BL／6J小鼠204只,分为8组：组1～组3（每组均为24只）分别吸30％氧气5、7．9d,组4～组6（每组均为24只）分别吸50％氧气5、7、9d,组7（n=30）吸75％氧气5d,组8（n=30）对照组在空气中生长。采用视网膜铺片法经ADP酶染色,观察吸氧后视网膜血管形态的动态改变;视网膜切片经常规HE染色,计数平均每只小鼠每张切片上突破视网膜内界膜的新生血管内皮细胞核数目,以定量反映视网膜血管的增生情况。结果（1）视网膜铺片结果：①FiO2为30％：吸氧5d或7d后视网膜血管形态全部正常;吸氧9d后深层血管网轻度阻塞,出氧箱2d后迅速恢复正常,至P21发育成熟。②FiO2为50％：吸氧5d后视网膜血管较明显收缩,视网膜中央较大区域无血管灌注,出氧箱2d后出现较多新生血管,但出氧箱5d后血管形态基本恢复正常;随着吸氧时间的延长,视网膜血管异常程度逐渐减轻,恢复更快。③FiO2为75％：吸氧5d后视网膜血管明显收缩,视网膜中央大片区域无血管灌注,出氧箱2d后出现新生血管,P17～P21达到高峰;延长吸氧时间后母、幼鼠死亡率明显上升。（2）视网膜切片结果：仅组7（FiO275％×5d）新生血管内皮细胞核数目达（41．9±2．8）个,与其余各组（均〈1个）差异有显著统计学意义（P〈0．0001）,其余各组间差异均无统计学意义。结论吸氧浓度和持续时间可影响视网膜血管的发育,长时间高浓度吸氧导致不可逆的血管增生性改变,临床上应尽量避免。     

新生大鼠高氧肺损伤血管内皮生长因子蛋白及其mRNA表达变化研究

目的：血管内皮生长因子（VEGF）参与肺的发育和损伤修复,VEGF具有促进肺泡和肺血管增殖以及预防新生儿支气管肺发育不良（BPD）的作用。该研究的目的是探讨新生大鼠高氧肺损伤后肺组织VEGF蛋白及VEGF mRNA表达的变化。方法：新生Sprague-Dawley大鼠48只随机分为高氧实验组和空气对照组,高氧实验组吸入95%以上高氧建立高氧肺损伤模型。分别采用免疫组化法和逆转录多聚酶链式反应（RT-PCR）检测新生大鼠3 d,7 d,14 d肺组织VEGF蛋白及VEGF mRNA表达变化。结果：空气对照组新生大鼠生后随着肺发育,肺组织中VEGF蛋白及VEGF mRNA表达逐渐增加。高氧实验组新生鼠吸入高氧3 d,肺VEGF蛋白表达出现降低,在7 d,14 d明显降低与对照组比较差异有显著性（VEGF 蛋白:12.67±3.82 vs 7.79±5.23; 15.10±8.91 vs 5.85±3.37, 均P<0.01）;高氧实验组VEGF mRNA表达在3 d,7 d,14 d均明显低于对照组（VEGF mRNA: 1.19±0.63 vs 0.78±0.22, 1.52±0.47 vs 0.53±0.18, 1.89±0.81 vs 0.48±0.12, 均P<0.01）。结论：VEGF能促进新生大鼠肺发育,VEGF蛋白及VEGF mRNA表达与新生大鼠肺发育有密切关系。高氧可抑制VEGF蛋白及VEGF mRNA在新生大鼠肺内的表达,VEGF在新生鼠肺发育和高氧肺损伤发病机制中起重要作用。     

高体积分数氧致慢性肺疾病早产鼠肺组织Foxa2的表达及其意义

目的 研究Foxa2在高体积分数氧(高氧)致慢性肺疾病早产鼠肺组织中的表达及意义.方法 将60只新生早产Wistar大鼠依据吸氧体积分数(FiO2)随机分为实验组(FiO2为950 mL·L-1)和对照组(FiO2为210 mL·L-1),每组30只,雌雄不限.每组分别于实验后的1 d、3 d、7 d随机选取10只早产鼠麻醉后处死,取材.光镜下观察肺组织病理改变,并对肺纤维化程度进行双盲评分;采用免疫组织化学法检测不同时间点大鼠肺组织Foxa2的表达.结果 1 d、3 d、7 d,对照组早产鼠肺组织发育逐渐成熟,肺泡结构逐渐规整,大小均匀,肺泡间隔变薄;实验组早产鼠肺组织逐渐出现肺泡间隔少而厚、少许炎性细胞渗出、部分肺间质纤维化.实验组1 d肺组织纤维化评分与对照组无明显变化,3 d、7 d肺组织纤维化评分明显高于对照组;肺组织Foxa2表达明显低于对照组,其与纤维化评分呈负相关(r=-0.70,P<0.05).结论 高氧可抑制早产鼠肺组织Foxa2表达,其异常表达可能导致肺组织发育受阻,进而发生肺损伤.     

The expression of aquaporin 8 and aquaporin 9 in fetal membranes and placenta in term pregnancies complicated by idiopathic polyhydramnios

Background

Aquaporins are a family of membrane-bound water channel proteins that regulate the flow of water across a variety of biological membranes. The expression of aquaporin 8 and aquaporin 9 has been demonstrated in human chorioamniotic membrane and placenta. But their roles in the pathophysiology of polyhydramnios are unclear.

Aims

To study the expression of aquaporin 8 and aquaporin 9 in fetal membranes and placenta in term pregnancies complicated by idiopathic polyhydramnios and to explore the association between aquaporin expressions and polyhydramnios.

Subjects

The placentas were collected from 51 patients who underwent elective Cesarean sections at term, of which 21 cases had idiopathic polyhydramnios and the other 30 had normal amniotic fluid volume.

Outcome measures

Real-time polymerase chain reaction and immunohistochemistry techniques were used to determine the expression and localization of aquaporin 8 and aquaporin 9 in the amnion, chorion and placenta.

Results

Expression of aquaporin 8 and aquaporin 9 was detected in the amnion, chorion and placenta and located in amnion epithelia, chorion cytotrophoblasts and placental trophoblast. Compared to normal amniotic fluid volume group, the expression of aquaporin 8 in amnion, and aquaporin 9 in amnion and chorion, were significantly increased in idiopathic polyhydramnios group; however, their expression in the placenta was significantly decreased.

Conclusions

When polyhydramnios occurs, expression of aquaporin 8 and aquaporin 9 in fetal membranes and placenta is an adaptive change, which may be involved in the regulation of amniotic fluid volume. However, the modulation factors of the aquaporin 8 and aquaporin 9 expressions need further study.     

不同发育阶段大鼠肺水通道蛋白表达的变化

目的：近年来研究发现组织发育与液体转运密切相关,水通道蛋白（AQPs）是一组与水主动转运有关的细胞膜转运蛋白,该文通过对AQPs在不同发育阶段大鼠肺脏表达变化的研究,探讨了AQPs在肺发育中的意义。方法：将Wistar大鼠分为4组：胎鼠组、新生鼠组、幼鼠组和成年鼠组,采用逆转录-聚合酶链反应（RT-PCR）和免疫组化（SABC）方法分别检测AQP1,AQP3,AQP4和AQP5 mRNA及其蛋白在肺细胞膜上的表达变化和分布;同时对肺发育相关指标进行对比分析。结果：大鼠肺发育连续不断,从胎鼠至新生鼠期增长最快,以后增速减慢,为一个动态的连续过程。肺AQPs mRNA在胎鼠时即有微量表达,出生后AQPs mRNA及蛋白含量迅速增加,呈增量表达至成年期;AQPs在肺组织的分布互不重迭,各有其独特的分布区域。AQPs变化与肺发育指标相关性分析显示它们间存在正相关（P<0.05）。结论： AQPs不仅涉及肺上皮的水转运,而且可能与肺组织发育有关。     

正常和肾积水胎儿肾脏水通道蛋白1-3的表达

目的 探讨正常和肾积水胎儿肾脏水通道蛋白1-3(AQP1-3)在孕中、晚期表达的差异.方法 收集本院母亲身体健康,因其他原因而引产的21例正常胎儿(孕中期12例,孕晚期9例)和9例孕晚期肾积水胎儿肾脏标本;应用免疫组织化学方法检测各组肾脏AQP1-3的定位与表达.同时采用Westem Blot检测正常和肾积水胎儿肾脏AQP1-3蛋白表达水平.同期收集本院8例成人因肾癌行肾切除术远离肿瘤的正常肾脏组织作为AQP1-3表达阳性对照.结果 免疫组化结果显示AQP1阳性染色主要分布于肾小球毛细血管内皮细胞、近曲小管的上皮细胞及髓袢降支细段上皮细胞胞质;AQP2阳性染色主要分布于肾脏集合管上皮细胞胞膜和胞质;AQP3阳性染色主要分布于肾脏集合管主细胞的基底侧.经Image-Pro Plus图像分析软件统计分析,孕中期肾脏AQP1-3表达分别为0.375±0.056、0.278±0.031和0.312±0.050,均弱于孕晚期组(分别为0.483±0.062、0.356±0.048和0.501±0.068),肾积水组AQP1-3表达分别为0.308±0.051、0.247±0.039和0.282±0.056,也均弱于同孕期正常胎儿,且胎儿肾脏AQP1-3表达均弱于成人对照组(分别为0.626±0.084、0.432±0.049和0.687±0.058,P＜0.05).Western Blot同样显示正常孕晚期胎儿AQP1-3蛋白表达量(0.96±0.07、0.94±0.06和0.95±0.05)显著高于孕中期(0.82±0.05、0.76±0.04和0.79±0.04),且高于同孕期肾积水组表达量(0.54±0.04、0.42±0.03和0.53±0.04,P＜0.05).结论 胎儿积水肾脏AQP1-3的表达水平较正常胎儿明显降低提示胎儿积水肾脏浓缩稀释功已经受损.     

Prevalence of overweight and obesity in children and adolescents in a county in Sweden

Overweight among young people in Sweden is increasing. The aim of the present study was to investigate the frequency of overweight and obesity based on body mass index (BMI) values among children and adolescents. Overweight was defined as a BMI value > or = 91st percentile and obesity as a BMI value > 98th percentile on an international reference BMI curve. The study population included boys and girls from four age groups: 9, 12, 15 and 18 y. The data consisted of self-reported measures of height and weight that were obtained from questionnaires used in a cross-sectional study in December 1997. A validation study was performed using a part of the study population. A total of 7011 (81.7%) participants completed the questionnaire. The correlation between self-reported estimations and objective measures of height and weight was high in the oldest age groups (0.88-0.98), but lower in the 9-y-old age groups (0.37-0.72). These self-reported estimations in the 9-y-olds were excluded from further analysis. It was found that 12.3%, 11.6% and 11.4% of the boys in the 12-, 15- and 18-y-old age groups and 6.8%, 5.5% and 4.8% of the girls in the same age groups were overweight and 7.9%, 8.9% and 7.3% of the boys and 5.1%, 4.2% and 3.9% of the girls were obese. Conclusion: The prevalence of overweight and obesity was found to be high in the study population and is a serious public health problem. The prevalence of obesity was significantly higher (p < 0.05) in 15-y-old boys living in rural areas than in city and town dwellers of the same age.     

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??Up to 650 000 deaths annually are associated with respiratory diseases from seasonal influenza??indicating the high burden of influenza and its substantial social cost to the world. The incidence of Influenza is high among children. Vaccine and antiviral medicine can both prevent influenza??and health education is always neglected. Neuraminidase inhibitor remains the main antiviral drug. During the management of influenza infections??doctors should pay great attention to its complications??especially pneumonia and encephalopathy.     

Dietary patterns in infancy and cognitive and neuropsychological function in childhood

Background: Trials in developing countries suggest that improving young children’s diet may benefit cognitive development. Whether dietary composition influences young children’s cognition in developed countries is unclear. Although many studies have examined the relation between type of milk received in infancy and subsequent cognition, there has been no investigation of the possible effect of variations in the weaning diet. Methods: We studied 241 children aged 4 years, whose diet had been assessed at age 6 and 12 months. We measured IQ with the Wechsler Pre‐School and Primary Scale of Intelligence, visual attention, visuomotor precision, sentence repetition and verbal fluency with the Developmental Neuropsychological Assessment (NEPSY), and visual form‐constancy with the Test of Visual Perceptual Skills. Results: In sex‐adjusted analyses, children whose diet in infancy was characterised by high consumption of fruit, vegetables and home‐prepared foods (‘infant guidelines’ dietary pattern) had higher full‐scale and verbal IQ and better memory performance at age 4 years. Further adjustment for maternal education, intelligence, social class, quality of the home environment and other potential confounding factors attenuated these associations but the relations between higher ‘infant guidelines’ diet score and full‐scale and verbal IQ remained significant. For a standard deviation increase in ‘infant guidelines’ diet score at 6 or 12 months full‐scale IQ rose by .18 (95% CI .04 to .31) of a standard deviation. For a standard deviation increase in ‘infant guidelines’ diet score at 6 months verbal IQ rose by .14 (.01 to .27) of a standard deviation. There were no associations between dietary patterns in infancy and 4‐year performance on the other tests. Conclusions: These findings suggest that dietary patterns in early life may have some effect on cognitive development. It is also possible that they reflect the influence of unmeasured confounding factors.