Inhaled nitric oxide attenuates hyperoxic lung injury in lambs

Cytochrome P450 (CYP) inhibition with cimetidine reduces hyperoxic lung injury in young lambs. Nitric oxide (NO), also a CYP inhibitor, has been shown to either aggravate or protect against oxidant stress depending on experimental context. The objective of this study was to determine whether NO, like cimetidine, would protect young lambs against hyperoxic lung injury, and whether its effect was associated with CYP inhibition. Three groups of lambs were studied: 1) room air exposure, 2) >95% O2, and 3) >95% O2 plus inhaled NO. After 72 h, hyperoxia alone resulted in a significant increase in arterial P(CO2) and number of polymorphonuclear leukocytes in bronchoalveolar lavage (BAL), and a significant decrease in arterial/alveolar O2 tension (a/A). The addition of inhaled NO significantly decreased the hypercarbia and BAL polymorphonuclear cellular response associated with hyperoxia but had no beneficial effect on a/A ratio. There were no significant differences in F2-isoprostanes or isofurans (markers of lipid peroxidation) measured in BAL or lung tissue among study groups. No intergroup differences were detected in BAL epoxyeicosatrienoic acid levels (index of CYP activity). The results of this study indicate that hypercarbia and inflammation accompanying hyperoxic lung injury in young lambs can be attenuated by inhaled NO. However, this study provides no direct evidence that NO is inhibiting CYP-mediated oxidant lung injury.     

促红细胞生成素对新生大鼠高氧肺损伤细胞凋亡的影响

目的：探讨人重组促红细胞生成素（rhEPO）对新生大鼠高氧肺损伤细胞凋亡的影响。方法：96只新生Sprague-Dawley大鼠随机分为4组：空气+生理盐水（NS）组,空气+rhEPO组,高氧+NS组,高氧+rhEPO组。后两组暴露于95%氧气中,高氧+rhEPO组于高氧暴露后2 d、4 d、6 d给予rhEPO 800 U /kg皮下注射, 空气+rhEPO组于同样时间点给予等量rhEPO。各组氧暴露后第3、7、14天随机抽取8只大鼠处死并取肺组织,苏木精-伊红染色观察病理变化,蛋白印迹法测定p-JNK水平,TUNEL法测定细胞凋亡。结果：与空气+NS组比较,高氧+NS组3 d出现肺泡炎性反应渗出,7 d更为明显,14 d出现肺泡数量减少,大小不均,肺大泡形成,高氧+rhEPO组的病理改变减轻,炎性反应细胞浸润减少。高氧+rhEPO组肺组织p-JNK水平较高氧+NS组有所减少,细胞凋亡减轻。结论：促红细胞生成素能通过减少细胞凋亡对新生大鼠高氧肺损伤起保护作用,其作用可能是通过JNK途径所介导。［中国当代儿科杂志,2010,12（7）：576-579］     

肌成纤维细胞与高氧肺损伤

氧疗是改善新生儿尤其是早产儿缺氧状态的一项重要措施，但长时间吸入高氧却可导致氧中毒，其中最直接的损害器官是肺脏，高氧肺损伤（hyperoxic lung injury）已成为危重新生儿救治的主要并发症之一。由于新生儿，特别是早产儿肺表面活性物质系统和抗氧化酶系统发育不成熟，高氧进入肺部后，将产生氧自由基，导致肺部炎症反应，组织损伤和异常修复，产生以炎症和纤维化为主要特征的另一并发症：支气管肺发育不良（bronchopulmonary dysplasia，BPD）。     

维甲酸与正常肺发育及高氧肺损伤

支气管肺发育不良是继发于机械通气的一种慢性肺病变,常发生于早产儿严重呼吸窘迫综合征需要长期应用高浓度氧气者,还见于其他辅助机械通气治疗的新生儿.高浓度氧吸入致肺损伤的理论已被公认,长时间吸入高浓度氧可以导致肺泡及肺血管发育受阻,肺间质纤维化.而维甲酸参与正常肺发育过程,可以改善支气管肺发育不良的肺发育阻滞,修复高氧肺损伤肺纤维化.该文对维甲酸参与肺正常发育及高氧肺损伤修复作一概述.     

血管内皮生长因子与高氧肺损伤

高氧肺损伤主要表现为肺泡II型上皮细胞生长受到抑制 ,肺的发育和成熟受阻。血管内皮生长因子 (VEGF)主要作用于血管内皮细胞 ,具有促进内皮细胞增殖、分化 ,增加微血管的通透性及诱导血管发生的功能。该文就VEGF在高氧肺损伤中的作用及高氧对VEGF的影响作一简要综述     

Effects of erythropoietin on hyperoxic lung injury in neonatal rats

Pulmonary oxygen toxicity is believed to play a prominent role in the lung injury that leads to the development of bronchopulmonary dysplasia (BPD). To determine whether human recombinant erythropoietin (rhEPO) treatment reduces the risk of developing BPD, we investigated the effect of rhEPO treatment on the histopathologic changes seen in hyperoxia-induced lung injury of BPD. Twenty-five rat pups were divided into four groups: air-exposed control group (n = 5), hyperoxia-exposed placebo group (n = 7), hyperoxia-exposed rhEPO-treated group (n = 6), and air-exposed rhEPO-treated group (n = 7). Measurement of alveolar surface area, quantification of secondary crest formation, microvessel count, evaluation of alveolar septal fibrosis, and smooth muscle actin immunostaining were performed to assess hyperoxia-induced changes in lung morphology. Treatment of hyperoxia-exposed animals with rhEPO resulted in a significant increase in the mean alveolar area, number of secondary crests formed, and the microvessel count in comparison with hyperoxia-exposed placebo-treated animals. There was significantly less fibrosis in rhEPO-treated animals. However, treatment of hyperoxia-exposed animals with rhEPO did not result in a significant change in smooth muscle content compared with hyperoxia-exposed placebo treated animals. Our results suggest treatment with rhEPO during hyperoxia exposure is associated with improved alveolar structure, enhanced vascularity, and decreased fibrosis. Therefore, we conclude that treatment of preterm infants with EPO might reduce the risk of developing BPD.     

抗氧化剂在新生鼠高氧肺损伤治疗中的作用研究

目前,普遍认为:高氧肺损伤与氧自由基(oxygen free radical,OFR)的活性、炎性细胞的激活[1]以及细胞因子的释放有关.SOD抗氧化作用的安全性及疗效已得到了肯定[2].U74389G作为一种合成21-氨基类固醇的抗氧化剂,是甲基强的松龙提取物,没有激素活性,具有高亲脂性,易穿过细胞膜,是有效的铁离子螯合剂及有效的脂质过氧化物阻碍者.有报道[3],U74389G通过抑制高氧肺氧自由基、减轻炎症而减轻肺损伤,本研究观察了抗氧化剂U74389G及SOD对高氧暴露新生大鼠肺内组织氧自由基的产生、脂质过氧化物丙二醛(malondialdehyde,MDA)的产生、SOD的活性、肺的病理改变及对肺细胞凋亡的影响而阐述高氧肺损伤的机理,以探讨两者的抗氧化作用及两者的疗效比较.     

Up-regulation of trypsin and mesenchymal MMP-8 during development of hyperoxic lung injury in the rat

Acute lung injury is marked by damage to alveolar-capillary barrier. High pulmonary levels of matrix-degrading serine proteinase trypsin and matrix metalloproteinases (MMP)-2, -8, and -9 have been shown in preterm infants with respiratory distress syndrome (RDS). We studied expression of trypsin and MMP-2, -8, and -9 in rats exposed to >95% oxygen for 24, 48, or 60 h. As demonstrated by zymography and Western immunoblotting, levels of trypsin and MMP-2, -8, and -9 in bronchoalveolar lavage fluid (BALF) sharply increased after 48 h of hyperoxia relative to normoxia controls. This coincided with increase in alveolar-capillary permeability, as indicated by increased protein concentration in BALF. Both neutrophil-derived 80-kD and mesenchymal cell-derived 60-kD MMP-8 isoforms were detected in BALF. Of them, mesenchymal-type MMP-8 predominated. In immunohistochemistry, alveolar epithelium showed strong trypsin expression at 48 and 60 h of hyperoxia, whereas it was predominantly negative in controls. MMP-8 was mostly expressed in macrophages. Marked up-regulation of trypsin and MMP-8 early during hyperoxic lung injury suggests that these enzymes play a role in the pathogenesis of acute lung injury and may therefore be potential targets for therapy of lung injury.     

N-乙酰半胱氨酸对新生大鼠急性高氧性肺损伤的保护作用

目的评价N-乙酰半胱氨酸(N-acetylcysteine,NAC)对新生鼠高氧肺损伤的保护作用并探讨其机制。方法将出生3～5 d的SD大鼠随机分为4组:①高氧 NAC组(NAC治疗组);②高氧 生理盐水组(高氧组);③空气 NAC组(NAC对照组);④空气 生理盐水组(空气组)。分别于实验3、7 d检测肺组织匀浆液中丙二醛(MDA)、谷胱甘肽过氧化酶(GSH-Px)的含量;比较肺湿/干重(W/D)以及肺组织病理改变;用ELISA法检测血清中α-肿瘤坏死因子(TNF-α)的含量;用免疫组化法对肺组织细胞黏附分子-1(ICAM-1)的表达进行定量研究。结果实验3 d时,高氧组的MDA、TNF-α以及ICAM-1的表达与空气组相比有显著升高(P<0.05),而GSH-Px活性降低;NAC治疗组与高氧组相比GSH-Px活性升高,其余各项指标均有明显的下降(P<0.01)。7 d时,与空气组相比,高氧组的W/D、MDA、TNF-α、ICAM-1均显著增高,而GSH-Px活性继续下降,NAC治疗组中以上各项指标的改变明显减轻。病理切片显示,3 d时高氧组肺即有炎性改变,7 d时损伤进一步加重,NAC治疗组病理改变明显减轻。结论NAC用于新生鼠高氧肺损伤的治疗,可以减轻肺水肿,减轻炎症反应,起到有效的保护作用。     

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.     

高氧致新生大鼠肺损伤过程中T淋巴细胞动态变化的研究

目的探讨高氧致新生大鼠肺损伤过程中T淋巴细胞的动态变化。方法新生12 h内的SD大鼠随机分为对照组、高氧组,对照组置于正常空气中喂养,高氧组持续暴露于80%～85%氧浓度下。两组分别于第1、4、7、14、21天时提取肺脏、脾脏和胸腺,以常规组织学方法观察肺脏形态结构变化;运用常规计数法检测脾脏中淋巴细胞数量变化;采用流式细胞术检测脾脏中CD4+、CD8+T细胞的百分比变化;以混合淋巴细胞反应检测脾淋巴细胞对植物血凝素(PHA)和自身肺组织的增殖反应;用常规组织学和免疫组织化学法观察胸腺形态结构变化及增殖细胞核抗原表达和CD4+、CD8+细胞分布。结果实验4 d时,高氧组CD4+、CD8+淋巴细胞百分比较对照组明显增多(P<0.01),7 d时CD4+淋巴细胞百分比明显高于对照组(P<0.01),此后CD4+、CD8+淋巴细胞百分比逐渐下降,到实验21 d时接近对照组。淋巴细胞活检发现,实验4～7 d时,脾淋巴细胞对自身肺组织和对PHA刺激的增殖反应活性较对照组均明显增高(P均<0.01);14～21 d时,脾淋巴细胞对自身肺组织刺激的增殖反应活性逐渐下降,但均明显高于对照组(P均<0.01),而对PHA刺激后...     

一氧化碳释放分子3通过抑制肺泡上皮细胞凋亡减轻脂多糖诱导的新生鼠急性肺损伤

目的 探讨一氧化碳释放分子3(CORM3)对脂多糖(LPS)诱导的新生鼠急性肺损伤(ALI)肺泡上皮细胞凋亡的影响。 方法 32只新生SD大鼠均分为对照组、LPS组、CORM3组和失活CORM3（iCORM3）组;LPS组、CORM3组和iCORM3组采用LPS气管内滴注建立新生鼠ALI模型,分别腹腔注射生理盐水、CORM3和iCORM3;对照组不建立ALI模型,腹腔注射生理盐水。于建模后12 h取肺组织,苏木素 伊红染色观察肺组织病理改变,湿干(W/D)比值测定,肺泡灌洗液(BALF)细胞计数及蛋白含量测定。体外培养A549细胞,LPS诱导细胞凋亡。MTT检测细胞活性,Tunel染色观察组织、细胞凋亡变化。 结果 ①与对照组相比,LPS组肺组织形态结构明显紊乱,肺泡压缩,肺间质大量炎性细胞浸润;CORM3组肺组织形态结构基本正常,间质炎性细胞浸润少;iCORM3组见肺组织水肿及大量炎性细胞浸润。②与对照组相比,LPS组肺组织W/D比值、BALF细胞数及蛋白含量明显升高,肺泡上皮细胞凋亡率明显增多［(37.3±4.5)% vs (3.0±1.0)%］;A549细胞活力下降,凋亡率明显升高［(29.6±4.1)% vs (3.6±1.0)%］,差异均有统计学意义 （P<0.05）。CORM3组肺组织W/D比值、BALF细胞数和蛋白含量较LPS组显著下降,肺泡上皮细胞凋亡率减少［（19.3±4.6）%］;A549细胞活力回升,凋亡率［（15.3±4.5）%］明显降低,差异均有统计学意义 （P<0.05）。LPS组与iCORM3组间上述指标差异均无统计学意义。 结论 CO通过抑制肺泡上皮细胞凋亡减轻新生鼠ALI     

血管内皮生长因子对早产大鼠高氧肺损伤保护作用的研究

目的 研究血管内皮生长因子(VEGF)在早产儿高氧肺损伤中的保护作用,寻找防治新生儿慢性肺疾病的新途径.方法 建立高氧肺损伤动物模型,对早产大鼠随机分为3组:空气对照组、高氧组和高氧+VEGF组,高氧组和高氧+VEGF组的氧浓度控制在90%以上.分别于第4、14天处死动物,用实时PCR的方法 检测肺组织VEGF和血小板内皮细胞黏附分子1(PECAM-1)mRNA的表达水平,HE染色对肺组织进行形态学观察.结果肺组织VEGF和PECAM-1 mRNA的表达水平在高氧组降低(P<0.05),而高氧+VEGF组与空气对照组比较差异无统计学意义(P>0.05).高氧组在第4天可见肺间质增宽,成熟的肺泡数目减少,可见较多囊泡.第14天时上述变化更加明显,成熟的肺泡少见.通过加用VEGF干预后.上述病变减轻.结论 VEGF对高氧肺损伤具有保护作用.     

重组人促红细胞生成素对新生大鼠高体积分数氧肺损伤细胞炎症的影响

目的探讨人重组促红细胞生成素(rhEPO)对新生大鼠高体积分数氧(高氧)肺损伤炎症的影响。方法将72只新生SD大鼠按随机数字表法分为4组:对照组、支气管肺发育不良(BPD)组、高氧+低剂量促红细胞生成素[EPO(L)]组、高氧+高剂量促红细胞生成素[EPO(H)]组。BPD组、高氧+EPO(L)组和高氧+EPO(H)组新生大鼠暴露于850 mL/L氧气中,高氧+EPO(L)组和高氧+EPO(H)组分别于高氧暴露后1、3、7 d给予800 IU/kg、2000 IU/kg rhEPO皮下注射,对照组和BPD组注射等量9 g/L盐水。实验开始后3、7、14 d记录各组体质量。HE染色,光镜下观察其肺组织形态结构的改变,检测肺组织放射状肺泡计数(RAC)。免疫荧光染色法检测核因子-κB(NF-κB)的表达,Western blot技术检测肺组织磷酸化NF-κB(pNF-κB)、抑制蛋白(IκB)及Caspase-3的表达,酶联免疫吸附试验(ELISA)检测支气管肺泡灌洗液中白细胞介素-1β(IL-1β)的表达。结果1.BPD组新生大鼠14 d时体质量明显低于对照组[(18.97±3.21)g比(27.97±2.30)g],差异有统计学意义(P<0.05);14 d时,高氧+EPO(L)组和高氧+EPO(H)组新生大鼠体质量[(24.16±2.15)g、(26.04±1.97)g]均显著高于BPD组,差异均有统计学意义(均P<0.05)。2.HE染色观察肺组织形态学结构显示,与对照组比较,BPD组3 d肺泡间隔有少量炎性细胞渗出,7 d更为明显,肺泡腔有渗出,14 d出现肺泡数量减少,肺大疱形成,间隔增厚,RAC明显减少(5.50±1.29比14.33±2.80),差异均有统计学意义(P<0.01);高氧+EPO(L)组和高氧+EPO(H)组新生大鼠肺组织病理改变减轻,炎性细胞浸润减少,RAC值在14 d均明显高于BPD组,差异均有统计学意义(均P<0.05)。3.免疫荧光结果显示,BPD组NF-κB p65阳性细胞数目明显增多,荧光强度增强,给予EPO处理后可减少NF-κB p65阳性细胞数目,荧光强度减弱。4.Western blot结果显示,与对照组比较,BPD组pNF-κB p65及Cleaved Caspase-3显著增高,差异均有统计学意义(均P<0.05);IκB明显降低,差异有统计学意义(P<0.05);与BPD组比较,高氧+EPO(L)组和高氧+EPO(H)组pNF-κB p65及Cleaved Caspase-3显著降低,差异均有统计学意义(均P<0.05),IκB均明显升高,差异均有统计学意义(均P<0.05)。5.ELISA结果显示,与对照组比较,BPD组IL-1β表达明显增加,差异有统计学意义(P<0.05);高氧+EPO(L)组和高氧+EPO(H)组IL-1β表达则显著低于BPD组,差异均有统计学意义(均P<0.05)。结论EPO能通过NF-κB途径抑制细胞炎性反应,减轻高氧诱导的肺组织凋亡,对新生大鼠高氧肺损伤起保护作用。     

前列腺素 E-1 对新生大鼠高氧肺损伤的作用及机制

目的探讨前列腺素E1(PGE-1)皮下注射对新生大鼠高氧肺损伤的治疗及机制。方法 45只新生Wistar大鼠随机分为对照组、高氧肺损伤模型组、高氧肺损伤+PGE-1组,每组15只。高氧肺损伤模型组、高氧肺损伤+PDE-1组置于氧浓度85%的实验舱内制作高氧肺损伤模型,对照组置于同气压下的空气中。对照组、高氧肺损伤模型组从生后第1天起皮下注射0.9%的Na Cl溶液,高氧肺损伤PGE-1组注射2μg/(kg·d)的PGE-1,均连续注射7天。观察肺干湿质量比,计数肺泡灌洗液(BALF)白细胞总数,HE染色观察支气管及肺泡的形态改变,核染色结合TUNEL查看肺组织凋亡,Western blotting法检测肺组织GRP 78、CHOP蛋白表达。结果对照组、高氧肺损伤模型组和高氧肺损伤+PGE-1组之间肺干湿质量比,BALF白细胞总数,细胞凋亡指数,肺组织GRP78、CHOP蛋白表达的差异均有统计学意义(P0.001),其中高氧肺损伤模型组上述指标最高,高氧肺损伤+PGE-1组居中,对照组最低,两两比较差异均有统计学意义(P0.05)。肺组织病理切片观察见高氧肺损伤模型组肺泡腔增大、融合,间质细胞水肿,可见纤维渗出;高氧肺损伤+PGE-1组介于高氧肺损伤模型组和对照组之间。结论 PGE-1皮下注射对新生大鼠高氧肺损伤有治疗作用,其机制可能与抑制CHOP、GRP 78蛋白表达有关。     

多西环素对新生鼠高氧肺损伤影响的体视学研究

Objective To explore the influence and potential protective effects of non-specific panMetrix Metalloproteinases(MMPs) inhibitor Doxycycline on hyperoxic lung injury and lung development in neonatal rats.Methods Neonatal SD rats were divided into 4 groups randomly within 12 hours after birth:air with normal saline(AN),air with doxycycline(AD),hyperoxia with normal saline(ON),and hyperoxia with doxycycline group(OD).Hyperoxia groups(ON and OD) were exposed to ≥90% O2.Doxycycline 20 mg/kg or equal volume of 0.9% saline(Doxycycline concentration 2 mg/ml) was administered by gastric gavage,twice daily from day 1 to experimental day,but it didn't exceed 14 days.Stereological study was carried out at day 1,3,7,14 and 21 after birth.Results Enlarged mean alveolar area was noted both in hyperoxia and Doxycycline groups.OD group had larger star volume than ON group on day 14.Except ON group,all other groups had increased alveolar septum and the condition was worsened by hyperoxia with Doxycycline.The percentage of collagen in lung parenchymal tissue in ON group increased persistently.This increasing trend was stopped in OD group on day 14,and collagen percentage had no significantly difference between OD and AN groups on day 14 and 21.Conclusion Both hyperoxia and Doxycycline influence neonatal lung development,percentage of coUgen in lung parenchymai can be reduced by Doxycycline in hyperoxic lung injury.     

Exudative lung injury is associated with decreased levels of surfactant proteins in a rat model of meconium aspiration

OBJECTIVE: Meconium aspiration syndrome remains a common cause of respiratory failure in neonates. The acute effects of meconium aspiration are inactivation of lung surfactant in vivo and in vitro. This study investigated the delayed effects of meconium on alveolar surfactant phospholipids and protein levels in spontaneously breathing animals. METHODS: Twenty-two adult rats were given 4.3 mg of dry weight human meconium after endotracheal intubation. Rats were briefly mechanically ventilated in room air, extubated, then killed after 16 (n = 6), 24 (n = 6), 48 (n = 6), and 72 hours (n = 4). Control animals received the same volume of normal saline (n = 7) or no meconium (n = 7). Bronchoalveolar lavage and tissue specimens were evaluated for inflammatory cells, total proteins, surfactant phospholipids, and surfactant proteins. RESULTS: Meconium caused exudative lung injury that was reflected in increased cell counts and proteins in alveolar lavage fluid. The peak injury occurred at 16 hours after instillation, whereas recovery occurred by 72 hours. Although total lavage fluid phospholipids did not change over time, phospholipid and dipalmitoyl phosphatidylcholine in large aggregates tended to decrease at 24 hours. Western blot analysis demonstrated time-dependent qualitative decreases in surfactant proteins A and B (SP-A, SP-B) in meconium-instilled animals compared with the controls. ELISA for SP-B confirmed the Western blot findings with total SP-B in large aggregate decreasing from 25 +/- 4 microg in controls to 6.6 +/- 0.8 microg at 24 hours of injury. CONCLUSIONS: Our study suggests that the exudative lung injury with meconium instillation is associated with decreased levels of SP-A and SP-B in the large aggregate fraction of lung surfactant. We speculate that decreased secretion and/or increased degradation accounts for lower levels of SP-B in bronchoalveolar lavage fluid.     

多西环素对新生鼠高氧肺损伤影响的体视学研究

Objective To explore the influence and potential protective effects of non-specific panMetrix Metalloproteinases(MMPs) inhibitor Doxycycline on hyperoxic lung injury and lung development in neonatal rats.Methods Neonatal SD rats were divided into 4 groups randomly within 12 hours after birth:air with normal saline(AN),air with doxycycline(AD),hyperoxia with normal saline(ON),and hyperoxia with doxycycline group(OD).Hyperoxia groups(ON and OD) were exposed to ≥90% O2.Doxycycline 20 mg/kg or equal volume of 0.9% saline(Doxycycline concentration 2 mg/ml) was administered by gastric gavage,twice daily from day 1 to experimental day,but it didn't exceed 14 days.Stereological study was carried out at day 1,3,7,14 and 21 after birth.Results Enlarged mean alveolar area was noted both in hyperoxia and Doxycycline groups.OD group had larger star volume than ON group on day 14.Except ON group,all other groups had increased alveolar septum and the condition was worsened by hyperoxia with Doxycycline.The percentage of collagen in lung parenchymal tissue in ON group increased persistently.This increasing trend was stopped in OD group on day 14,and collagen percentage had no significantly difference between OD and AN groups on day 14 and 21.Conclusion Both hyperoxia and Doxycycline influence neonatal lung development,percentage of coUgen in lung parenchymai can be reduced by Doxycycline in hyperoxic lung injury.     

多西环素对新生鼠高氧肺损伤影响的体视学研究

Objective To explore the influence and potential protective effects of non-specific panMetrix Metalloproteinases(MMPs) inhibitor Doxycycline on hyperoxic lung injury and lung development in neonatal rats.Methods Neonatal SD rats were divided into 4 groups randomly within 12 hours after birth:air with normal saline(AN),air with doxycycline(AD),hyperoxia with normal saline(ON),and hyperoxia with doxycycline group(OD).Hyperoxia groups(ON and OD) were exposed to ≥90% O2.Doxycycline 20 mg/kg or equal volume of 0.9% saline(Doxycycline concentration 2 mg/ml) was administered by gastric gavage,twice daily from day 1 to experimental day,but it didn't exceed 14 days.Stereological study was carried out at day 1,3,7,14 and 21 after birth.Results Enlarged mean alveolar area was noted both in hyperoxia and Doxycycline groups.OD group had larger star volume than ON group on day 14.Except ON group,all other groups had increased alveolar septum and the condition was worsened by hyperoxia with Doxycycline.The percentage of collagen in lung parenchymal tissue in ON group increased persistently.This increasing trend was stopped in OD group on day 14,and collagen percentage had no significantly difference between OD and AN groups on day 14 and 21.Conclusion Both hyperoxia and Doxycycline influence neonatal lung development,percentage of coUgen in lung parenchymai can be reduced by Doxycycline in hyperoxic lung injury.