Connexin40 Modulates Pulmonary Permeability Through Gap Junction Channel in Acute Lung Injury After Thoracic Gunshot Wounds
Connexin40 Modulates Pulmonary Permeability Through Gap Junction Channel in Acute Lung Injury After Thoracic Gunshot Wounds
复制标题
Connexin40 通过间隙连接通道调节胸部枪伤后急性肺损伤的肺通透性。
DOI：
10.1097/ta.0b013e3181bb80ea
复制
发表时间：
2010-04-01
影响因子：
--
通讯作者：
Yi, Dinghua
中科院分区：
文献类型：
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作者：
Li, Qiang;Zhang, Jinzhou;Yi, Dinghua
背景
急性肺损伤后，肺微血管内皮细胞的通透性通过细胞旁间隙增加。缝隙连接蛋白40是肺微血管内皮细胞缝隙连接通道的主要成分，介导细胞间的通讯。然而，连接蛋白40与肺微血管内皮细胞通透性的关系尚不清楚。因此，我们研究了连接蛋白40是否影响兔急性肺枪伤后肺微血管内皮细胞的通透性。
方法
我们采用新西兰兔胸部火器伤后急性肺损伤模型，并将火器伤肺组织中连接蛋白40免疫组化与伊文思蓝渗漏率进行相关性研究。培养的肺微血管内皮细胞分为对照组（G control）、损伤血清组（G serum）和阻断剂组（G blocker）。通过刮片加载和染料转移技术评估间隙连接通道功能。采用伊文思蓝白蛋白转移法测定肺微血管内皮细胞通透性。
结果
Cx40表达呈时间依赖性下降，而伊文思蓝渗漏率增加。Cx40表达与伊文思蓝渗漏率呈强负相关（γ =-0.934，p < 0.05）。损伤血清使缝隙连接通道功能降低，差距连接通道阻断剂加重了这种作用。同样，肺微血管内皮细胞的通透性增加显着G血清和G阻滞剂。
结论
火器伤致急性肺损伤后肺微血管内皮细胞缝隙连接蛋白40表达下调这与间隙连接通道功能受损和肺微血管内皮细胞通透性增加有关。
BACKGROUND
The permeability of pulmonary microvessel endothelial cells increases markedly after acute lung injury via paracellular gap. Connexin40 is a primary component of pulmonary microvessel endothelial cells gap junction channel and mediates intercellular communication. However, the relationship between connexin40 and the permeability of pulmonary microvessel endothelial cells is still unknown. Therefore, we determined whether connexin40 affected rabbits' pulmonary microvessel endothelial cells permeability after acute lung injury induced by gunshot trauma.
METHODS
We used an acute lung injury model in New Zealand rabbits following gunshot chest trauma and correlated connexin40 immunohistochemistry in gunshot lung tissue with Evans blue leak rate. Cultured pulmonary microvessel endothelial cells were divided into three groups, control (G control), injured serum (G serum), and blocker agent (G blocker). Gap junction channel function was assessed by scrape-loading and dye transfer techniques. Pulmonary microvessel endothelial cells permeability was measured by Evans blue-labeled albumin transfer.
RESULTS
Connexin40 expression decreased time dependently, whereas Evans blue leak rate increased. Connexin40 expression and Evans blue leak rate exhibited a strong inverse correlation (gamma = -0.934, p < 0.05). Injured serum decreased gap junction channel function, and the gap junction channel blocker aggravated this effect. Similarly, pulmonary microvessel endothelial cells permeability increased significantly in G serum and G blocker.
CONCLUSIONS
Connexin 40 expression in pulmonary microvasculature endothelial cells is downregulated after acute lung injury induced by gunshot trauma. This is associated with impaired gap junction channel function and increased pulmonary microvessel endothelial cells permeability.