肺血管的发育及解剖生理特点

肺血管血容量约占心血管系统的9%，对维持人体呼吸功能和心脏循环的稳定起着重要作用。肺血管的先天发育异常和解剖生理功能的紊乱均可导致肺血管疾病，如肺动脉高压、肺栓塞、肺血管炎等。因此，了解肺血管的发育及解剖生理学特征对肺血管疾病的发病机制研究至关重要。     

甲状腺转录因子-1在人胎肺和新生儿肺上皮细胞中的时序表达

目的：甲状腺转录因子1(TTF1)作为重要的调控上皮细胞特异性基因表达的同源核转录因子,对促进胎肺发育起重要作用。TTF1在人胎肺发育过程中的表达规律尚不清楚。该文旨在检测TTF1在人胎肺发育过程中的时序表达,探讨其在胎肺上皮细胞发育、分化过程中的调控作用。方法：由孕妇自愿捐献的胎龄为10～27周胎肺组织32例及死亡新生儿正常肺组织7例(28～36周),用免疫组织化学技术检测TTF1的表达。结果：TTF1在胎肺第10周已开始表达,定位于上皮细胞核内,在远端呼吸道上皮表达丰富;随着支气管的发育分化,TTF1阳性细胞散在分布于支气管上皮中的无纤毛细胞,在远端支气管上皮细胞核中强表达,尤其是在新生支气管芽的尖端;在胎肺发育末期及新生儿肺中,TTF1阳性反应在Ⅱ型肺泡上皮细胞和肺泡前体细胞中稳定表达,纤毛细胞和Ⅰ型肺泡上皮细胞无表达。结论：TTF1参与支气管树形态发生和肺泡的发育成熟,并调控Ⅱ型肺泡上皮细胞及肺泡前体细胞分泌肺表面活性物质,与适应出生后执行功能的需要密切相关。     

血管内皮生长因子及其受体与肺发育的研究进展

肺发育受多种因素影响,其中血管内皮生长因子(VEGF)是一种特异作用于血管内皮细胞的生长因子,具有促进血管内皮细胞增殖分化、新生血管形成、增加微血管通透性的功能,并通过其受体介导参与肺血管发育、肺泡形成、表面活性物质合成和肺成熟等,在建立正常肺形态和功能上发挥重要作用,表达异常可致肺发育异常.     

内皮素与胎肺发育及新生儿持续性肺动脉高压

内皮素 (ｅｎｄｏｔｈｅｌｉｎ ,ＥＴ)是迄今所发现的作用最强的内源性血管收缩肽 ,在心血管、肺、肾、肝、脑等脏器的疾病发生中 ,组织或血浆ＥＴ浓度有不同程度升高 ,ＥＴ在许多疾病发生中的作用日渐受到重视。肺是内皮素含量最丰富的器官 ,也是内皮素合成、代谢的主要场所。ＥＴ对气道平滑肌细胞、上皮细胞、肺血管平滑肌细胞、肺泡上皮细胞、成纤维细胞的功能活动均有调控作用。本文对ＥＴ 1在胎肺发育及新生儿持续性肺动脉高压 (ＰＰＨＮ)中的作用作一综述。1　内皮素及其受体在肺内分布　　ＥＴ由Ｙａｎａｇｉｓａｗａ在 1988年分离、…     

儿童肺血管疾病的影像学诊断

肺血管疾病是一组累及包括各级肺动、 静脉及肺毛细血管在内的肺循环疾病， 其致病因素各异， 病理改变多样。儿童与成人肺血管疾病从致病因素、 发病机制、 病理生理学， 临床表现及预后等方面均存在较大差异。儿童肺血管性疾病包括以下几大类别： （1）先天性肺血管病变，包括各级别的肺动、 静脉畸形、 肺毛细血管发育异常、 气管支气管畸形伴肺血管畸形、 血管淋巴异常等； （2）肺血管栓塞性病变， 包括炎症性栓塞， 肿瘤性栓塞； （3）肺血管炎性病变； （4）肺动脉高压性病变； （5） 肺部血管源性肿瘤。儿童常见肺血管疾病常用的影像学检查方法有胸部X线平片、 超声心动图、 胸部CT增强扫描、 肺血管造影检查、 核医学肺通气/灌注显像等。该文对上述儿童常见肺血管疾病影像学检查方法的选择及影像学诊断要点进行概述。     

一氧化氮与早产儿慢性肺病变

早产儿慢性肺疾病是早产儿吸入高浓度氧、机械通气治疗后最常见的并发症,严重影响患儿的生活质量.长时间吸入高浓度氧可以导致肺泡及肺血管发育受阻,炎症介质激活等,而NO可能在调节肺部炎症、肺血管张力及细胞凋亡等方面参与早产儿慢性肺疾病的发生发展.该文将对NO在早产儿慢性肺病变中的作用进行概述.     

早产儿支气管肺发育不良的病因及发病机制新进展

支气管肺发育不良是一种与早产相关的慢性肺部疾病,有较高的病死率和再入院率,目前尚缺乏有效的预防和治疗方法.它的病因尚不明确,目前认为是在遗传易患性的基础上,肺发育不成熟、肺损伤和损伤后的异常修复引起.肺部町见明显的炎症细胞及炎症因子的浸润,存在细胞的坏死和凋亡,同时在蛋白质水平及基因水平均有所改变.     

高浓度氧肺损伤机制研究进展

吸入高浓度氧常被用于多种疾病的救治 ,以保证组织对氧的需求 ,但长时间吸入高氧的同时也会引起肺结构和功能的异常 ,以致影响生活质量[1] ,甚至危及生命 ;对正在发育中的肺组织 ,高氧甚至会导致其不可逆的畸形发育。随着对高氧肺损伤机制研究的不断深入 ,发现高氧除产生过量的氧自由基损伤肺组织外 ,还可能存在其他途径的致伤作用 ,如高氧通过引起肺部炎症反应、细胞凋亡、组织异常修复等途径导致肺结构和功能的异常。一、炎症反应研究发现 ,吸入高氧后 ,肺部表达多种炎症介质 ,这些炎症介质能介导肺部炎症反应 ,引起肺组织损伤 ,及功能减…     

Wnt信号通路与支气管肺发育不良

Wnt信号通路是一条在进化上保守的信号传导途径,主要由经典的Wnt/β-catenin途径和非经典的Wnt/平面细胞极性途径及Wnt/Ca2+途径组成,该通路从多个水平参与肺发育及多种肺部疾病过程.支气管肺发育不良(bronchopulmonary dysplasia,BPD)是在肺发育不成熟基础上由于炎症损伤及损伤后肺纤维化异常修复所导致的慢性肺疾病.该文就Wnt信号通路与肺发育、肺部炎症和肺纤维化的关系作一综述,以期揭示Wnt信号通路与BPD之间的可能联系,为BPD的防治提供新的切入点.     

Claudin-18对早产儿支气管肺发育不良作用的研究进展

支气管肺发育不良（bronchopulmonary dysplasia,BPD）早期以肺水肿为主要表现,晚期出现特征性的肺泡化受阻和微血管发育不良,可能由肺上皮屏障的结构和功能破坏引起。Claudin蛋白是紧密连接的主要成分,参与调节细胞旁离子和溶质渗透性。Claudin-18是目前唯一已知的肺特异性紧密连接蛋白,其缺乏可导致肺部屏障功能障碍和肺泡发育受损,其敲除可出现BPD的特征性组织学病理变化。该文将从肺上皮通透性、肺泡发育及肺部祖细胞稳态3个方面阐释Claudin-18在BPD发生发展中扮演的重要角色,旨在对BPD的发病机制研究和临床治疗提供新思路。     

基于文献挖掘的高氧损伤肺组织相关基因的生物信息学分析

目的 比较小鼠高氧肺损伤肺组织与正常肺组织的差异表达基因,从分子水平揭示高氧肺损伤的发病机制.方法 利用PubMed数据库获取小鼠高氧肺损伤肺组织与正常肺组织的差异表达基因,并进行生物学通路、基因本体和功能注释聚类等生物信息分析.结果 两组间差异表达基因共467条,以2倍标准筛选出189条差异表达基因,再用功能注释工具将超过2倍差异表达的基因对KEGG数据库进行映射,共有54条基因注释到KEGG数据库的小鼠生物学通路中.通过代谢通路的富集度分析,有5条通路显示具有相关性,提示这些途径可能和高氧肺损伤密切相关.5条通路中与高氧肺损伤相关基因20条（上调基因14条,下调基因6条）,它们在造血细胞的增殖、分化、更新,轴突导向,细胞之间的黏着连接,T细胞受体信号转导通路,黏着斑形成方面起着重要作用.结论 对挖掘出的20条与高氧肺损伤相关的基因进行深入研究,将为揭示高氧肺损伤的分子机制和靶向治疗提供有效方法.     

MicroRNA在肺部疾病中的研究进展

已知MicroRNA是调控细胞分化代谢、机体生长发育的关键。近年来,针对肺发育和肺部疾病的发生发展机制以及诊断和治疗肺部疾病如肺癌、慢性阻塞性肺疾病等方面有关MicroRNA的研究取得了较多进展,该文就MicroRNA在肺部疾病的最新研究情况作一综述。     

Varied presentations of unilateral lung hypoplasia and agenesis: a report of four cases

Unilateral lung hypoplasia or agenesis can be asymptomatic or␣present with recurrent respiratory symptoms. The latter may be amenable to surgical treatment in␣selected cases. Of four children in this report, two are being managed without surgery. A third was relieved of his symptoms by pneumonectomy. The fourth presented with acute foreign-body inhalation into the healthy right main bronchus, and coexistent left pulmonary agenesis was discovered at bronchoscopy. Bronchoscopy and computed tomography were found to be the most useful investigations in management. Accepted: 3 November 1997     

Retinoic acid rescues lung hypoplasia in nitrofen-induced hypoplastic foetal rat lung explants

There is increasing evidence to suggest that the retinoid pathway is involved in the pathogenesis of congenital diaphragmatic hernia (CDH). We hypothesised that retinoids are involved in the pathogenesis of associated pulmonary hypoplasia in CDH and therefore designed this study to investigate the effects of retinoid acid on nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9.5 of gestation. Foetal lungs were harvested on embryonic day 13.5 and were cultured for 96 h with or without exogenous retinoic acid (RA) (1 μM) added daily to the culture medium. Lungs were divided into four study groups: control (n=31); control + RA (n=19); nitrofen (n=19); and nitrofen + RA (n=12). Lung growth was assessed in each group by measuring branching morphogenesis, total DNA content and the proportion of proliferating cells stained by immunohistochemistry. One-way ANOVA test was used for statistical analysis. Retinoic acid significantly increased the growth of nitrofen-induced hypoplastic lungs, whilst growth of control lungs did not change. The number of lung buds and lung area of nitrofen-exposed hypoplastic lungs after 96 h of culture significantly increased after the addition of RA compared to the non-treated hypoplastic lungs (25.75±6.47 vs 15.11±3.29 and 0.98±0.18 mm² vs 0.65±0.13 mm², respectively; P<0.0001). Lung perimeter was also higher when RA was added to hypoplastic lungs compared to the non-treated ones, although it did not reach significance (12.51±2.53 mm vs 11.19±2.56 mm; P=0.17). Conversely, the addition of RA to control lungs did not affect the number of lung buds, lung area or lung perimeter after 96 h in culture compared to the non-treated ones (31.28±4.66 vs 31.81±6.67; 1.29±0.18² vs 1.29±0.23 mm² and 18.47±3.47 mm vs 17.89±2.94 mm, respectively; P=NS). Retinoic acid also increased the total DNA content and the proportion of proliferating cells in hypoplastic lungs compared to the non-treated ones (2.59±0.58 μg vs 1.96±0.31 μg and 57.89±9.46% vs 36.76±8.15%, respectively; P<0.001). The addition of RA did not affect either total DNA content or the proportion of proliferating cells in control lungs compared to the non-treated ones (4.04±0.64 μg vs 3.79±0.85 μg and 58.67±11.23% vs 56.03±10.36%, respectively; P=NS). This study demonstrates for the first time that RA rescues lung hypoplasia in nitrofen-induced hypoplastic lungs. These results suggest that retinoid pathway may be involved in the pathogenesis of associated pulmonary hypoplasia in CDH.     

Early protein oxidation in the neonatal lung is related to development of chronic lung disease

Free radical-mediated oxidation of proteins may impair their function and cause cellular damage. We studied pulmonary protein oxidation and its association with the development of chronic lung disease in 61 newborn infants (mean gestational age 31.1 ± 4.0, range 24-41 weeks) requiring intensive care with oxygen therapy. Protein oxidation was quantified as protein carbonylation in tracheal aspirates recovered daily during the first week of life. Mean carbonyl concentration was 3.5 ± 1.6 μmol/mg protein. Negative correlations existed between protein carbonylation during days 2-4 and gestational age (day 2: r = -0.37, p = 0.01; day 3: r = -0.48, p = 0.001; and day 4: r = -0.33, p = 0.03). Patients who developed bronchopulmonary dysplasia showed significantly higher protein carbonylation on days 1-6 (all p < 0.05). In multiple regression analysis explaining bronchopulmonary dysplasia, using gestational age, inspired oxygen on days 1-3 and protein carbonylation on day 3 as independent variables, only protein carbonylation remained significant. We conclude that immaturity is the most important factor explaining free radical-mediated pulmonary protein oxidation in newborn infants and that oxidation of proteins is related to the development of chronic lung disease.     

Rare tumors of the lung in children

The authors report rare and different types of lung tumors in 4 children. The first case is an 8-year-old boy with mucoepidermoid carcinoma, the second case is a 9-year-old girl with neuroendocrine carcinoma, the third is a 14-year-old girl with fetal lung adenocarcinoma (FLAC), and the last is a 16-year-old girl with bronchioloalv eolar carcinoma. Among these tumors, FLAC has not been reported in children so far. Each tumor type displayed a different prognosis in the follow-up period. In the differential diagnosis of primary lung tumors, carcinoid tumor, bronchogenic carcinoma, and pulmonary blastoma are frequently encountered, but these rare tumor types should be borne in mind.     

Lung liquid,fetal lung growth,and congenital diaphragmatic hernia

There is now a large body of evidence supporting the role of lung liquid in normal and experimental fetal lung growth. It is clear that tracheal ligation causes retention of lung liquid increased intratracheal pressure, and lung hyperplasia and that this hyperplastic effect can reverse the experimental pulmonary hypoplasia of clinically relevant entities such as congenital diaphragmatic hernia. Most importantly, this reversal is both structural and physiologic, as these lungs are more compliant and capable of normal gas exchange. In clinical cases of pulmonary hypoplasia, focusing initial therapy on active promotion of lung growth by exploiting a mechanism that may be a part of normal pulmonary development offers some hope of improved outcome in a group of patients that are currently unsalvageable.     

Surgical treatment of pediatric lung abscess

Eight pediatric patients with lung abscesses underwent surgical intervention in our hospital during a 7-year period. All the abscesses were associated with severe sepsis or complicated by a bronchopleural fistula that did not respond to medical treatment and tube thoracostomy. Seven patients required unilateral thoracotomies, and one patient with bilateral lesions required simultaneous bilateral thoracotomies. One tension pneumatocele required a preceding pneumonostomy. All patients underwent decortication and at least one additional surgical procedure consisting of: lung debridement plus bronchial closure (n = 4); lobectomy (n = 2); bisegmentectomy (n = 3); and/or segmentectomy (n = 1). There were no operative deaths, but two patients had persistent air leakage that was treated by bronchial closure. The average hospital stay was 22 days (postoperative 10.1 days). All the patients recovered completely. For many pediatric lung abscesses that do not respond to medical treatment and simple drainage procedures, surgical intervention is indicated and can shorten the hospital stay.     

间隙连接蛋白与肺部疾病的研究进展

间隙连接蛋白是与细胞新陈代谢、增殖、分化等生理过程密切相关的一种膜蛋白,在肺中表达丰富.近年来研究发现间隙连接蛋白参与肺纤维化、肺损伤、肺肿瘤等多种肺疾病的病理生理过程.该文对间隙连接蛋白分子特点、生物学功能、在肺中的分布及其与肺疾病的关系进行综述.     

保护性肺通气对婴儿围体外循环期肺功能的影响

目的 观察体外循环(CPB)中间断肺通气对婴儿肺功能的影响.方法 选取60例1岁以内行室间隔缺损修补术的患儿,分为2组:对照组(n=30)于CPB开始后停止通气;处理组(n=30)于CPB开始心脏停跳后膨肺[用手挤压气囊,使气道压力升到15～20 cm H2O(1 cmH2O=0.098 kPa),维持3～5 s,重复5次],将肺内血液排出,然后静态膨肺(3～5 cm H2O),并每隔10 min膨肺5次.两组患儿均于腔静脉开放后恢复机械通气.检测CPB开始前及CPB结束后2、6、12、24和48 h共6个时点的氧合指数、动脉血氧分压/肺泡氧分压、肺泡-动脉氧分压差和呼吸指数等肺功能指标.结果 在CPB后2、6、12 h,处理组氧合指数、动脉血氧分压/肺泡氧分压高于对照组(P＜0.05);在CPB后2、6、12、48 h,处理组肺泡-动脉氧分压差低于对照组(P＜0.05);在CPB后6、12 h,处理组呼吸指数低于对照组(P＜0.05).结论 在婴儿CPB过程中持续静态膨肺并间断压力膨肺,可以改善术后早期肺的氧合功能,有较好的肺保护作用.