Temporal Expression of Notch in Preterm Rat Lungs Exposed to Hyperoxia

Summary: To explore the mechanism of Notch in hyperoxia-induced preterm rat lung injury, 2-days-old preterm SD rats were randomized into control and hyperoxia group (FiO 2≥0.85). On day 1, 7, 14 and 21, 8 rat pups of each time point were used to assess histopathological changes of lung with HE staining and to evaluate the expression of Notch1 and Notch3 with immunohistochemistry. Notch1, Notch3, Aquaprin5 (AQP5) and surfactant protein C (SP-C) mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). The results showed that the lung injury in the hyperoxia group was characterized by retarded lung alveolization and differentiation of alveolar epithelial type Ⅱcells (AEC Ⅱ). Positive staining of Notch1 in hyperoxia group was weaker than controls at every time point (except for day 7), while positive staining of Notch3 was much stronger (P<0.05, P<0.01). Notch1, Notch3 mRNA level showed similar change as protein level. AQP5, SP-C mRNA decreased significantly as compared with that of the controls (P<0.01). We are led to conclude that hyperoxia results in abnormal expression of Notch, which is likely to contribute to the pathogenesis of lung injury through regulating proliferation and transdifferentiation of alveolar epithelial cells.

Comparison of Respiratory Outcome between Sustained Lung Inflation and Intermittent Positive Ventilation in Preterm Infants Requiring Resuscitation at Birth

Background: Sustained lung inflation (SLI) would permit lung recruitment immediately after birth, improving lung mechanics and reducing the need for intubation and subsequent respiratory support in the neonatal intensive care unit among preterm infants. Aim of the Study: To assess the efficacy of initial sustained lung inflation compared to standard intermittent positive pressure ventilation (IPPV) in preterm infants who need resuscitation in delivery room. Methods: This was prospective randomized observational study that was conducted in the delivery room and NICU of A in shames University hospital from February 2019 to September 2019. The study included 115 preterm infants between 26 - 32 weeks of gestation who needed resuscitation at delivery room. The infants were randomly allocated into 2 groups;SLI group: included the preterm infants who received the SLI at initial inflation pressure of 25 cm H2O for 15 seconds using the Neopuff/T piece. IPPV group: preterm infants who received standard resuscitation;IPPV using the self-inflating bag. The heart rate (HR), oxygen saturation (SpO2), oxygen requirement, and intubation rate as well as need of surfactant in the delivery room were assessed. All cases were evaluated after admission to the NICU for the need of mechanical ventilation in the first 72 hours of life, death in delivery room or NICU and for bronchopulmonary dysplasia or death at 36 weeks post menstrual age (PMA). Results: The percentage of preterm infants who needed resuscitation was 25.5% from the total deliveries during the study period. 56.5% of them received SLI and 43.4% received conventional IPPV. There were no significant differences between the studied groups regarding gestational age, birth weight. Apgar score, heart rate, oxygen saturation was not significantly increased in the SLI group at fifth minutes of age. The percentage of infants who needed further resuscitation was 20% in SLI group and 12% in the IPPV group. There were no significant differences in need for surfactant, CPAP or ventilator among the studied groups. There were no significant differences in relation to complications as BPD, air leak or retinopathy and death between the two groups. Conclusion: This study showed that there was no advantage from use of SLI in delivery room using T-piece upon the conventional IPPV using self-inflating bag.

Lamellar Bodies Count (LBC) as a Predictor of Fetal Lung Maturity in Preterm Premature Rupture of Membranes Compared to Neonatal Assessment

Background: Respiratory distress syndrome (RDS) is a major cause of neonatal morbidity and mortality, affecting approximately 1% of all live births and 10% of all preterm infants. Lamellar bodies represent a storage form of pulmonary surfactant within Type II pneumocytes, secretion of which increases with advancing gestational age, thus enabling prediction of the degree of FLM. Preterm premature rupture of membranes (PPROM) complicates approximately 1/3 of all preterm births. Birth within 1 week is the most likely outcome for any patient with PPROM in the absence of adjunctive treatments. Respiratory distress has been reported to be the most common complication of preterm birth. Sepsis, intraventricular haemorrhage, and necrotizing enterocolitis also are associated with prematurity, but these are less common near to term. Objective: To assess the efficacy of the amniotic fluid lamellar body counting from a vaginal pool in predicting fetal lung maturity in women with preterm premature rupture of membranes. Methods: This study was conducted at Ain Shams University Maternity Hospital in the emergency ward from January 2019 to September 2019. It included 106 women with singleton pregnancies, gestational age from 28 - 36 weeks with preterm premature rupture of membranes. This study is designed to assess the efficacy of the amniotic fluid lamellar body counting (LBC) from a vaginal pool in predicting fetal lung maturity in women with preterm premature rupture of membranes. Results: The current study revealed a highly significant increase in the lamellar body count in cases giving birth to neonates without RDS compared to that cases giving birth to neonates with RDS. Also, no statistically significant difference between LBC and age, parity and number of previous miscarriages in the mother was found. Gestational age at delivery was significantly lower among cases with respiratory distress. Steroid administration was significantly less frequent among cases with respiratory distress. However, lamellar bodies had high diagnostic performance in the prediction of respiratory distress. Conclusion: Lamellar body count (LBC) is an effective, safe, easy, and cost-effective method to assess fetal lung maturity (FLM). It does not need a highly equipped laboratory or specially trained personnel, it just needs the conventional blood count analyzer. Measurement of LBC is now replacing the conventional Lecithin/Sphyngomyelin L/S ratio. LBC cut-off value of ≤42.5 × 103/μL can be used safely to decide fetal lung maturity with sensitivity of 95.7% and specificity of 97.6%.

Effects of Hyperoxia on Mitochondrial Multienzyme Complex Ⅲ and Ⅴ in Premature Newborn Rat Lung

To investigate the effects of hyperoxia on mitochondrial multienzyme complex Ⅲ （cytochrome, Cytb） and Ⅴ （ATPase6, 8） in premature newborn rat lung, the 1-day-old preterm SD rats were randomly assigned to hyperoxia group and air group, The rats in hyperoxia group were continuously exposed to 85% oxygen and those in air group to room air. After 1, 4, 7, 10, 14 day（s） of exposure, these rats were killed, total lung RNA was extracted and Cytb, ATPase6, 8 mRNA were detected by reverse transcription polymerase chain reaction （RT-PCR）. Western blotting was used to detect the expression of Cytb protein in lung tissue. The results showed that compared with air group, Cytb mRNA expression was significantly increased （P〉0,05） after 1, 4 day（s） of exposure. The general tendency decreased after 7 days, and its expression became weak but difference in mRNA expression between the two groups was not significant （P〉0.05）. ATPase6 mRNA expression was significantly increased 1 day after the exposure （P〈0.05） and did not show any significant change 4, 7, 10 days after the exposure （P〉0.05）. At the 14th day, ATPase6 mRNA expression was significantly increased （P〈0.05）, ATPase8 mRNA expression did not show any significant change 1, 4, 10 day（s） after the exposure （P〉0.05）, At the 7th and 14th day, ATPase8 mRNA expression was significantly increased （P〈0.05）. Western blotting showed that Cytb protein expression was increased 1,4 day（s） after the exposure, but the difference between the two groups was not significant （P〉0.05）. The general tendency was decreased after 7 days, and its expression became weak but difference was not significant 7, 10 days after the exposure （P〉0.05）. At day 14 its expression became significantly weak （P〈0.05）. We are led to conclude that exposure to high concentrations of oxygen can significantly change the expression of Cytb and ATPase6, 8, which results in uncoupling of oxidative phosphorylation in mitochondrial respiration chain, and plays an important role in the mechanism of hyperoxia-induced lung injury.

晚期早产儿与足月新生儿的潮气呼吸肺功能特点及其影响因素分析

目的对比研究晚期早产儿与足月新生儿的潮气呼吸肺功能特点,以探讨影响新生儿呼吸系统发育水平的相关因素。方法选择2019年5月-2020年12月福建医科大学附属第一医院新生儿科收治的140例晚期早产儿(出生时胎龄34~36^(+6)周)和足月新生儿(出生时胎龄37~41^(+6)周)作为研究对象。所有新生儿出生后第7天,使用Jaeger MasterScreen设备进行新生儿肺功能检测。记录新生儿的一般资料和相关实验室指标,以及新生儿的潮气呼吸肺功能观察指标,包括潮气量(tidal volume,TV)、每公斤体重潮气量(tidal volume/kilogram,TV/kg)、分钟通气量(minute ventilation,MV)、达峰时间比(ratio of time to peak tidal expiratory flow to total expiratory time,TPTEF/TE)、达峰容积比(ratio of volume to peak tidal expiratory flow to total expiratory volume,VPTEF/VE)、呼气中期流速与吸气中期流速比(ratio of the expiratory to the inspiratory flow rate when exhaling and inhaling 50%of the tidal breath volume,TEF50/TIF50)。结果140例新生儿中,晚期早产儿31例(男20例、女11例),胎龄(35.54±0.89)周,出生体重(2.52±0.46)kg;足月新生儿109例(男65例、女44例),胎龄(39.26±1.10)周,出生体重(3.32±0.44)kg。晚期早产儿的TV、MV均显著低于足月新生儿(P值均<0.01),而两组间TV/kg、VPTEF/VE、TPTEF/TE、TEF50/TIF50的差异均无统计学意义(P值均>0.05)。身长≥50 cm、校正胎龄≥37周、出生时体重3.0~3.5 kg和>3.5 kg、检查时体重3.0~3.5 kg和>3.5 kg、血清白蛋白30~35 g/L和>35 g/L的新生儿TV和MV均显著高于身长<50 cm、校正胎龄<37周、出生时体重<3.0 kg、检查时体重<3.0 kg、血清白蛋白<30 g/L的新生儿(P值均<0.01)。其他变量亚组间TV和MV的差异均无统计学意义(P值均>0.05)。将单因素分析中差异有统计学意义的因素作为自变量,分别以TV、MV为因变量,进行多元线性回归分析。结果显示,检查时体重和校正胎龄均是新生儿TV、MV变化的影响因素(P值均<0.05),而非身长、出生体重和血清白蛋白水平(P值均>0.05)。结论检查时体重、校正胎龄是影响新生儿肺功能发育的相关因素,临床医师和新生儿家长应密切关注新生儿尤其是早产儿的生长发育情况,这对提升新生儿肺发育水平具有重要意义。

超声监测下管理肺疾病:或使早产儿支气管肺发育不良成为可避免的疾病

支气管肺发育不良(bronchopulmonary dysplasia,BPD)是早产儿最常见的慢性肺部疾病,虽然对其病因、机制、预防和治疗的研究取得了重要进展,但预后并没有明显改善。BPD患儿不仅病死率高,对存活者也造成呼吸、神经、心脏等多方面的持久性损害。作者团队在肺脏超声监测下管理新生儿肺疾病,在过去近7年的时间里避免了BPD的发生,为BPD的预防开辟了新途径。该文对此予以简介,以期加强相关研究,为预防或最大程度减少BPD的发生提供更加科学的管理方案。

肺超声评分对晚期早产儿并发呼吸窘迫综合征应用机械通气及肺表面活性物质的预测价值

目的:探讨使用肺超声评分(LUS)对晚期早产儿并发呼吸窘迫综合征(RDS)应用机械通气(MV)和肺表面活性物质(PS)的预测价值。方法:选择并发RDS的晚期早产儿(胎龄34^(0/7)~36^(6/7)周)进行前瞻性分析,共纳入67例并发RDS的晚期早产儿。根据患儿生后48 h内是否需要应用MV和PS,分为MV组(n=36)、非MV组(n=31)、PS组(n=30)和非PS组(n=37)。各组患儿在入院后2 h和应用PS前进行肺超声检查,并分别计算6分区、10分区和12分区LUS。绘制不同分区LUS预测晚期早产儿并发RDS应用MV和PS的受试者工作特征(ROC)曲线,采用Delong检验比较不同分区方法的预测价值。结果:与非PS组比较,PS组患儿出生体质量、LUS、呼气末正压(PEEP)、平均气道压(MAP)、MAP×吸入氧浓度(FiO_(2))/动脉血分压(PaO_(2))比值、呼吸机使用时间和住院时间均升高(P<0.05或P<0.01),PaO_(2)/FiO_(2)比值降低(P<0.01)。与非MV组比较,MV组患儿出生体质量、LUS、PEEP、MAP、MAP×FiO_(2)/PaO_(2)值、呼吸机使用时间和住院时间均升高(P<0.05或P<0.01),PaO_(2)/FiO_(2)比值降低(P<0.01)。6分区LUS测PS应用时,PEEP、MAP和LUS是晚期早产儿并发RDS应用PS的危险因素[比值比(OR)>1,P<0.05]。10分区和12分区LUS预测PS应用时,MAP×FiO_(2)/PaO_(2)比值和LUS是晚期早产儿并发RDS应用PS的危险因素(OR>1,P<0.05)。6分区、10分区和12分区LUS预测MV应用时,MAP和LUS是晚期早产儿并发RDS应用MV的危险因素(OR>1,P<0.05)。6分区、10分区和12分区LUS预测晚期早产儿并发RDS的ROC曲线下面积(AUC)分别为0.909、 0.904和0.915,均具有较好的预测价值;使用6分区、10分区和12分区LUS预测晚期早产儿并发RDS应用MV的AUC分别为0.868、0.872和0.887,均具有较好的预测价值。结论:LUS可有效预测晚期早产儿并发RDS是否需要应用MV和PS,MAP联合LUS可以提高单独使用LUS预测应用MV的能力。

早产儿支气管肺发育不良及远期肺功能与出生时维生素D水平的关系

目的分析早产儿出生时维生素D水平与支气管肺发育不良(BPD)及远期肺功能的关系。方法选取2018年6月至2020年3月本院新生儿重症监护室内的120例早产儿,检测所有早产儿血清维生素D水平,对所有早产儿于2岁时进行随访,检测其肺功能指标达峰时间比(TPTEF/TE)、达峰容积比(VPTEF/VE)及呼吸峰流速(PEF)水平。Spearman分析血清维生素D水平与BPD的关系,Pearson分析血清维生素D水平与2岁时肺功能指标TPTEF/TE、VPTEF/VE、PEF的关系。结果与非BPD组早产儿比较,BPD组早产儿血清维生素D水平明显降低(P<0.05)。不同BPD等级患儿血清维生素D水平差异有统计学意义(P<0.05),随着BPD病情严重程度增加,患儿血清维生素D水平逐步降低。与非BPD组早产儿比较,BPD组早产儿2岁时肺功能指标TPTEF/TE、VPTEF/VE、PEF均明显降低(P<0.05)。不同BPD等级患儿2岁时肺功能指标TPTEF/TE、VPTEF/VE、PEF均差异有统计学意义(P<0.05),随着BPD病情严重程度增加,患儿肺功能指标TPTEF/TE、VPTEF/VE、PEF逐步降低。早产儿血清维生素D水平与BPD呈明显负相关(r=-0.659,P<0.05)。早产儿血清维生素D水平与2岁时肺功能指标TPTEF/TE、VPTEF/TE、PEF均呈明显正相关(r=0.254、0.232、0.265,P<0.05)。结论早产儿出生时维生素D水平与BPD及远期肺功能均密切相关,早产儿出生时维生素D缺乏能够用于评估BPD发展进程并预测患儿的远期预后水平。

枸橼酸咖啡因高维持剂量对改善早产儿呼吸暂停通气治疗的影响研究

目的观察高剂量枸橼酸咖啡因辅助机械通气治疗早产儿呼吸暂停(AOP)的效果及安全性。方法选取2020年6月至2023年3月南阳市中心医院收治的123例AOP患儿进行随机对照试验,采用随机数字表法将入组患儿分为常规组(61例)和高剂量组(62例),两组患儿均接受持续气道正压通气治疗,常规组予以5 mg/kg枸橼酸咖啡因辅助通气治疗,高剂量组予以10 mg/kg枸橼酸咖啡因维持剂量辅助通气治疗,比较两组患儿的治疗情况、呼吸暂停症状改善情况、肺功能改善情况及治疗安全性。统计学方法采用χ^(2)检验、t检验。结果高剂量组的通气时间、用氧时间、重症监护病房(ICU)停留时间、住院时间均低于常规组[(4.25±1.33)d比(5.28±1.77)d、(4.02±1.47)d比(5.14±1.46)d、(5.12±1.36)d比(6.65±2.43)d、(10.25±3.41)d比(14.15±5.26)d],差异均有统计学意义(t=3.65、4.24、4.32、4.89,均P<0.05)。高剂量组治疗24 h、48 h、72 h的呼吸暂停发作频率均低于常规组[(8.44±2.23)次比(9.77±2.42)次、(6.36±1.47)次比(7.85±2.26)次、(3.25±0.76)次比(4.49±1.47)次],差异均有统计学意义(t=3.17、4.34、5.89,均P<0.05)。治疗后,高剂量组的潮气量、达峰时间比、达峰容积比均高于常规组[(8.62±2.41)ml/kg比(7.33±2.25)ml/kg、(36.77±10.61)%比(30.25±10.42)%、(35.66±10.33)%比(29.77±10.41)%],差异均有统计学意义(t=3.07、3.44、3.15,均P<0.05)。治疗后,高剂量组的不良事件发生率低于常规组[8.06%(5/62)比6.56%(4/61)],差异无统计学意义(χ^(2)=0.19,P=0.661)。结论高剂量枸橼酸咖啡因辅助机械通气治疗AOP可在有效改善患儿呼吸暂停症状的同时加快康复进程,与常规维持剂量相比,高维持剂量下的枸橼酸咖啡因未明显增加不良事件发生风险,安全性较高。

肺表面活性物质辅助机械通气对早产儿呼吸窘迫综合征的治疗效果分析

目的:探究肺表面活性物质(Pulmonary surfactant,PS)辅助机械通气治疗早产儿呼吸窘迫综合征(Neonatal respiratory distress Syndrome,NRDS)的临床疗效、肺功能和安全性的影响.方法:选取2020年5月至2023年9月在本院收治的NRDS患儿62例为研究对象,根据治疗方案不同分为对照组30例(常规治疗基础上实施机械通气)和观察组32例(在对照组基础上联合PS治疗).比较两组NRDS患儿临床疗效、治疗前后肺功能[肺动态顺应性(Dynamic lung Compliance,CD)、氧合指数(Oxygenation index,PaO_(2)/FiO_(2))、吸气阻力(Inspiratory resistance,RAWO)]指标变化、住院时间、呼吸机使用时间和并发症发生率.结果:治疗后,观察组治疗总有效率明显高于对照组(P<0.05).治疗后,两组CD、PaO_(2)/FiO_(2)均显著上升,RAWO均显著下降,且观察组CD、PaO_(2)/FiO_(2)明显高于对照组,RAWO明显低于对照组(P<0.05).治疗后,观察组平均住院时间、平均呼吸机使用时间均明显短于对照组,且并发症总发生率明显低于对照组(P<0.05).结论:PS辅助机械通气治疗NRDS可以促进患儿肺功能恢复,提高临床疗效,且安全性较高.

85%高浓度氧长期暴露诱发早产大鼠肺损伤(英文)

目的探讨长期高浓度氧(85％)暴露对早产新生大鼠肺组织的损伤作用。方法早产SD大鼠生后第2天被随机分为Ⅰ空气组、Ⅱ高氧组(置85％O2中)。分别于暴露3,7,14 d后,检测支气管肺泡灌洗液(BALF)中总蛋白(TP)、丙二醛(MDA)、羟脯氨酸(HYP)含量和细胞总数及分类,肺组织湿重/干重(W/D),肺组织胶原含量;于暴露3,7,14,21 d后,行肺组织病理学检查和辐射状肺泡计数(RAC)。结果3 d时Ⅱ组仅MDA含量增加(P<0.05);7,14 d时,Ⅱ组BALF中MDA,TP,HYP含量、细胞总数、细胞分类中性粒细胞所占比例及肺W/D均明显增加(P<0.05或<0.01)。两组肺胶原含量差异无显著性(P>0.05)。除3 d外,Ⅱ组肺组织病理学检查可见不同程度的肺泡炎改变和肺发育滞后。7 d时Ⅱ组RAC值较Ⅰ组明显减少[(5.9±0.9)vs(7.1±0.9)](P<0.05);14,21 d时RAC值Ⅱ组较Ⅰ组[(7.0±0.8)vs(9.9±0.6);(7.3±0.9)vs(10.5±0.8)]减少更明显(P<0.01)。结论85％O2长期暴露,可引起早产新生大鼠亚急性炎症性肺损伤和肺发育受抑。

Notch受体在早产鼠高氧肺损伤中的动态表达

目的检测Notch受体、AQP5、SP-C在高氧暴露下早产SD大鼠肺的表达,探讨Notch在高氧肺损伤中的作用机制。方法SD早产鼠80只随机分为对照组和高氧组,于1、71、42、1 d行肺组织病理学检查;免疫组织化学法检测Notch1、Notch3;RT-PCR检测Notch1、Notch3、AQP5S、P-C mRNA;Western blot检测AQP5、SP-C。结果病理学检查显示,高氧组肺发育滞后,Ⅱ型上皮细胞(AECⅡ)分化抑制。免疫组织化学法检测结果显示,高氧组各时间点(除7 d)肺组织Notch1表达低于对照组(P<0.05,0.01),Notch3上调(P<0.01)。Notch1、Notch3 mRNA改变类似蛋白水平。高氧组AQP5,SP-C mRNA及蛋白较对照组显著下降。结论85%高氧导致早产鼠肺Notch受体表达异常。Notch信号可能通过调控转分化参与高氧肺损伤。

mir-124-3p/SPOCK2在急性呼吸窘迫综合征早产儿血浆中表达的临床研究

目的 :探讨测定急性呼吸窘迫综合征早产儿血浆中mir-124-3p和SPOCK2蛋白的临床意义,为早产儿严重肺损伤寻找新的高危因子和治疗靶标。方法:根据早产儿呼吸窘迫综合征(respiratory distress syndrome,RDS)诊断标准,早产儿分成RDS组17例及对照组(无RDS等并发症的普通早产儿)21例。采用ELISA和Western blot法测定外周血浆中和体外培养的人肺成纤维细胞中的SPOCK2蛋白。采用Target Scan分析与SPOCK2基因3′末端非编码区结合的可能mi RNA,并用荧光实时定量RTPCR扩增候选mi RNA。采用Pearson统计方法对血浆中SPOCK2蛋白和mi RNA进行相关分析。构建mir-124-3p慢病毒载体,并转染人肺成纤维细胞,研究mir-124-3p过表达对SPOCK2蛋白表达的影响。结果:对照组早产儿血浆中SPOCK2蛋白浓度为(7.24±0.43)μg/L,而RDS组升高为(16.43±0.54)μg/L,两组间比较差异有统计学意义(t=12.81,P<0.01)。SPOCK2基因3′末端存在mir-124-3p、mir-25-3p、mir-122-5p等候选的mi RNA结合位点。荧光定量RT-PCR证实外周血中不能测到mir-25-3p、mir-122-5p。mir-124-3p表达在对照组中较高,在RDS组中显著降低,差异有统计学意义(P<0.05)。并且mir-124-3p的表达量与SPOCK2蛋白血浆水平呈负相关(r=-0.645 9,P=0.012 6)。mir-124-3p慢病毒载体转染可以显著抑制人肺成纤维细胞中SPOCK2蛋白的表达。结论:测定早产儿血浆中SPOCK2蛋白,可能对RDS等肺疾病的病情评估有一定临床意义。利用mir-124-3p调控SPOCK2蛋白表达,可能对早产儿RDS等严重肺损伤的治疗有潜在应用价值。

仰俯卧位对早产儿肺炎患儿肺功能的影响

目的探讨仰俯卧位对早产儿肺炎患儿肺功能的影响。方法应用美国BicoreCP-100新生儿肺功能仪分别对30名不吸氧组(SaO2≥90%)和18名吸氧组(SaO2<90%)早产儿肺炎患儿的肺功能值进行检测。结果不吸氧组患儿俯卧位呼吸频率明显低于仰卧位(43.4±10.2v49.8±11.7);俯卧位潮气量明显高于仰卧位(3.11±0.92v2.48±0.77ml/kg);俯卧位气道阻力明显低于仰卧位(98.6±50.1v117.4±41.5cmH2O/L/s,);俯卧位动态肺顺应性明显高于仰卧位(1.115±0.401v0.914±0.48ml/cmH2O/kg);俯卧位呼吸功明显高于仰卧位(8.0±3.8v5.9±2.7gmcm/kg)。吸氧组患儿俯卧位呼吸频率明显低于仰卧位(52.7±10.2v56.1±12.4);潮气量明显高于仰卧位(2.13±0.42v1.79±0.66ml/kg);俯卧位气道阻力明显低于仰卧位(290.4±107.0v319.1±104.1cmH2O/L/s);俯卧位动态肺顺应性明显高于仰卧位(0.562±0.192v0.488±0.217ml/cmH2O/kg);俯卧位呼吸功明显高于仰卧位(10.1±4.7v7.3±3.4gmcm/kg)。结论无论吸氧与否俯卧位均可提高患儿的潮气量、动态肺顺应性和呼吸功,降低呼吸频率和气道阻力,俯卧位为早产儿肺炎患儿的适宜体位。

吸入一氧化氮在早产儿的临床应用及实验研究

近年来吸入一氧化氮(NO)的新应用指征研究集中在早产儿慢性肺病(CLD)防治的有效性方面。临床大样本单中心或多中心研究揭示其对降低CLD发生,甚至减少颅内损害也有潜在影响,在出生体重>1000g的早产儿相对更明显。在多数研究中所采用的吸入NO剂量为5×10-6容量体积以下,1～2周连续吸入治疗。更多的安全性研究将依据长期随访结果,目前临床尚不作为常规治疗,但是对于比较难治愈的CLD,或有呼吸机相关性肺炎风险时,可以考虑将该治疗方法作为研究性使用。

早产大鼠高氧暴露下肺组织TNF-αCaspase-3表达时相研究

目的探讨肿瘤坏死因子α(TNFα)及半胱氨酸蛋FB白酶3(Caspase3)在早产大鼠高氧肺损伤中的动态表达及其意义。方法孕21d的SD早产大鼠生后第2天,随机分为空气组和高氧组(均n=40)。高氧组大鼠予以85%高氧持续暴露,空气组大鼠置于空气中。于高氧暴露1d、4d、7d、14d和21d每组各处死8只大鼠,收集肺组织标本,苏木精-伊红染色观察肺组织病理形态学变化,双抗夹心ELISA法检测TNFα含量,免疫组化和Westernblot检测Caspase3表达。结果高氧暴露4d、7d和14d肺组织TNFα和Caspase3含量明显增高(均P<0.01),且两者之间具有显著相关性(r=0.93,P<0.01)。结论TNFα诱导Caspase3过度表达导致细胞凋亡可能是早产大鼠高氧肺损伤的发病机制之一。

动态肺部超声监测早产儿机械通气治疗拔管期中的临床价值

目的探讨采用动态肺部超声监测早产儿(<34孕周)机械通气治疗围拔管期中的作用和临床价值。方法纳入2014年1月~2017年7月125例需行机械通气治疗的<34孕周的早产儿进入本研究,随机分为超声指导组57例和非超声指导组68例,分析比较两组间机械通气拔管的成功率、安全性及拔管后不良反应发生率。结果超声指导组机械通气拔管成功率明显高于非超声指导组(93.0%vs.76.5%,P=0.014),其中超声指导组机械通气拔管显效明显高于非超声指导组(56.1%vs.32.4%,P=0.011),非超声指导组机械通气拔管无效率高于超声指导组(22.0%vs.7.0%,P=0.024)。拔管后不良反应比较,超声指导组拔管后心动过速、烦躁不安、喂养不耐受明显低于非超声指导组(分别为5.3%vs.16.2%,P=0.048,3.5%vs.14.7%,P=0.032和19.1%vs.7.0%,P=0.042),电解质紊乱、高血糖发生率在两组间无统计学差异(P>0.05)。结论连续动态肺部超声监测能评估<34孕周早产儿肺部病变的进程,可辅助机械通气量和拔管时机的选择、指导不同剂量枸橼酸咖啡因药物剂量应用于拔管,并能提高拔管成功率,降低拔管中和拔管后出现的不良反应。

慢性肺疾病患儿外周血17个免疫细胞因子的研究

目的通过研究早产儿慢性肺疾病外周血17个细胞因子的改变,探讨早产儿慢性肺疾病的部分免疫发病机制。方法将26例住院满28d的早产儿分为慢性肺疾病组(14例)和对照组(12例),用multi-plex技术检测外周血中17个细胞因子(IL-1b,IL-2,IL-4,IL-5,IL-6,IL-7,IL-8,IL-10,IL-12,IL-13,IL-17,GM-CSF,IFN-γ,TNF-α,G-CSF,MCP-1,MIP-1b)的表达水平。结果慢性肺疾病组外周血中的17个细胞因子与对照组相比均无统计学差异(P>0.05)。结论早产儿慢性肺疾病发病后期的发病机制主要不是免疫因素造成的。

谷氨酰胺抑制早产高氧肺损伤大鼠肺组织的炎症反应及其机制

目的研究谷氨酰胺对早产高氧肺损伤大鼠肺部炎症反应的影响及机制。方法制备早产高氧肺损伤大鼠模型,给予谷氨酰胺处理。利用Diff-Quik染色检测大鼠支气管肺泡灌洗液中炎症细胞聚集情况,HE染色观察早产高氧肺损伤大鼠肺组织的炎症变化,TUNEL染色观察早产高氧肺损伤大鼠肺组织的细胞凋亡情况,ELISA检测支气管肺泡灌洗液(BALF)中白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)水平,Western blot法检测肺组织中丝裂原活化蛋白激酶磷酸酶1(MKP-1)、丝裂原活化蛋白激酶(MAPK)及胞质磷脂酶A2(cPLA2)的磷酸化水平。结果谷氨酰胺处理可以抑制肺部炎症反应和细胞凋亡,减少IL-1β和TNF-α的表达,促进MKP-1的磷酸化,抑制MAPK的激活和cPLA2磷酸化,减轻肺部炎症,缓解早产高氧大鼠肺组织肺炎症损伤。结论谷氨酰胺通过调节MKP-1/MAPK信号通路抑制早产高氧肺损伤大鼠肺部炎症反应。

新生儿期潮气呼吸参数、功能残气量及肺清除指数的动态研究

目的探讨不同孕周新生儿潮气呼吸参数、功能残气量及肺清除指数参数值随日龄变化的规律,探讨新生儿期肺功能变化与肺发育的关系。方法深圳市儿童医院新生儿科2010年2月至2014年11月住院新生儿中,选取足月儿55名,晚期新生儿30名和胎龄小于34周的早产儿25名,剔除标准为肺部感染、氧依赖、先天性心脏病、隔疝等影响肺功能的疾病。在生后第1、7、14、28日龄时,检测肺功能参数。结果三组新生儿RR值均随日龄增长而逐渐下降,VT/kg、MV/kg、TEF75值均随日龄增长而逐渐上升(均P<0.05);FRC/kg值随日龄增长而上升,LCI值随日龄增长而下降(均P>0.05);TPTEF/TE、VPEF/VE值则无明显的趋势变化(均P>0.05)。结论足月儿及早产儿在新生儿期肺功能指标变化基本一致,均随日龄增长而逐步改善。肺容量指标变化较快,通气功能指标则改变较慢,提示肺发育在新生儿期以容量增长为首选。证明新生儿肺功能检测是评价肺发育的重要手段。