Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40.
Hyperoxia arrests pulmonary development in newborn rats via disruption of endothelial tight junctions and downregulation of Cx40.
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高氧通过破坏内皮紧密连接和下调 Cx40 抑制新生大鼠的肺部发育
DOI：
10.3892/mmr.2014.2192
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发表时间：
2014-07
影响因子：
3.4
通讯作者：
Xue X
中科院分区：
文献类型：
--
作者：
Li C;Fu J;Liu H;Yang H;Yao L;You K;Xue X
本研究探讨了新生大鼠高氧诱导支气管肺发育不良（BPD）肺水肿早期血管内皮细胞紧密连接结构和连接蛋白40（Cx40）基因表达的变化。将96只新生大鼠随机分为高氧组（n = 48）和对照组（n = 48）。第一组建立高氧诱导的BPD模型，而对照组大鼠维持在常氧条件下。观察各组大鼠肺组织伊文思蓝（EB）渗出量、肺损伤程度、肺血管内皮细胞紧密连接结构、免疫组化、Western blotting和逆转录-聚合酶链反应（RT-PCR）检测Cx40 mRNA和蛋白表达。我们的研究结果表明，由于BPD的伤害是逐步加强在暴露于高氧条件下的时间过程中。高氧组肺血管通透性在第5天达到最高水平，与对照组相比显著升高。透射电镜观察显示内皮细胞之间的紧密连接非常紧密。在高氧组中，在第1天和第3天未发现紧密连接结构的明显变化;在第5天和第7天，内皮细胞之间可见细胞旁间隙。免疫组化染色显示Cx40蛋白主要表达于肺组织血管内皮细胞。蛋白质印迹和RT-PCR分析表明，Cx40的表达逐渐减少，这取决于暴露时间高氧条件。然而，Cx40 mRNA水平在第5天达到低谷。总之，我们的研究表明，暴露于高氧损伤血管内皮细胞之间的紧密连接结构和下调Cx40。因此，我们认为高氧可能参与了肺血管内皮细胞通透性的调节。
This study investigated changes in vascular endothelial cell tight junction structure and the expression of the gene encoding connexin 40 (Cx40) at the early pneumonedema stage of hyperoxia-induced bronchopulmonary dysplasia (BPD) in a newborn rat model. A total of 96 newborn rats were randomly assigned to one of the following two groups, the hyperoxia group (n=48) and the control group (n=48). A hyperoxia-induced BPD model was established for the first group, while rats in the control group were maintained under normoxic conditions. Extravasation of Evans Blue (EB) was measured; the severity of lung injury was assessed; a transmission electron microscope (TEM) was used to examine the vascular endothelial cell tight junction structures, and immunohistochemical assay, western blotting and reverse transcription-polymerase chain reaction (RT-PCR) were used to evaluate the expression of Cx40 at the mRNA and protein level. Our findings showed that injuries due to BPD are progressively intensified during the time-course of exposure to hyperoxic conditions. Pulmonary vascular permeability in the hyperoxia group reached the highest level at day 5, and was significantly higher compared to the control group. TEM observations demonstrated tight junctions between endothelial cells were extremely tight. In the hyperoxia group, no marked changes in the tight junction structure were found at days 1 and 3; paracellular gaps were visible between endothelial cells at days 5 and 7. Immunohistochemical staining revealed that the Cx40 protein is mainly expressed in the vascular endothelial cells of lung tissue. Western blotting and RT-PCR assays showed a gradual decrease in Cx40 expression, depending on the exposure time to hyperoxic conditions. However, the Cx40 mRNA level reached a trough at 5 days. Overall, our study demonstrated that exposure to hyperoxia damages the tight junction structures between vascular endothelial cells and downregulates Cx40. We therefore conclude that hyperoxia may participate in the regulation of pulmonary vascular endothelial permeability.
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影响因子：
3.9
作者：
Iles KE;Song W;Miller DW;Dickinson DA;Matalon S
通讯作者：
Matalon S
影响因子：
9.3
作者：
Elzarrad MK;Haroon A;Willecke K;Dobrowolski R;Gillespie MN;Al-Mehdi AB
通讯作者：
Al-Mehdi AB
影响因子：
1.7
作者：
Simon, AM;McWhorter, AR;Ouellette, Y
通讯作者：
Ouellette, Y
影响因子：
2.1
作者：
Trembath A;Laughon MM
通讯作者：
Laughon MM
影响因子：
3
作者：
Jobe, Alan H.;Kallapur, Suhas G.
通讯作者：
Kallapur, Suhas G.