ASYMMETRICAL EFFECTS OF INCREASES IN HYDROSTATIC-PRESSURE ON MACROMOLECULAR MOVEMENT ACROSS THE AIRWAY MUCOSA - A STUDY IN GUINEA-PIG TRACHEAL TUBE PREPARATIONS
ASYMMETRICAL EFFECTS OF INCREASES IN HYDROSTATIC-PRESSURE ON MACROMOLECULAR MOVEMENT ACROSS THE AIRWAY MUCOSA - A STUDY IN GUINEA-PIG TRACHEAL TUBE PREPARATIONS
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DOI：
10.1111/j.1365-2222.1991.tb00813.x
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发表时间：
1991-01-01
影响因子：
6.1
通讯作者：
PERSSON, CGA
中科院分区：
文献类型：
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作者：
GUSTAFSSON, BG;PERSSON, CGA
本研究采用离体豚鼠气管导管标本，研究静水压力的增加对大分子溶质(荧光素异硫氰酸酯偶联葡聚糖；FITC-D，分子量70kD；保存在浆膜或粘膜洗涤液中)跨粘膜移动的影响。发现在基线零压差条件下，浆膜FITC-D的腔内进入大于腔内FITC-D的浆膜进入，这证明了粘膜屏障的不对称性。此外，浆膜压力的增加(5 Cm H2O)将大量的浆膜FITC-D移入管腔，而施加于管腔一侧的相应压力仅略微增加了管腔内FITC-D的粘膜交叉点。通过将管腔压力提高到10和20 cm H2O(在患者体内可用作呼气末正压(PEEP))，腔内FITC-D的粘膜渗透与低(5 Cm H2O)浆膜压升高所引起的相反方向的粘膜渗透一样显著。从检测浆膜压力增加对腔内FITC-D粘膜穿透的影响的实验中，可以明显看出呼吸道粘膜屏障不对称的另一个方面。无论是在浆膜压力持续升高期间还是之后，腔内FITC-D穿过粘膜的程度都比基线零压条件下更大。这一发现与体内数据一致，表明血浆渗入气道腔可能与腔内溶质吸收增加无关。目前的结果支持血浆渗出物本身通过以下机制为其管腔进入创造通道的可能性：通过略微增加上皮下流体静压，实现了对上皮细胞的横向压缩效应，从而使顶端紧密连接也分离，以允许不同大小的血浆溶质的大量流动；这是上皮细胞向外通透性的明显增加，当压力降低时，紧密连接重新聚集；因此，在渗出过程中和之后，粘膜保持其完整性，作为管腔溶质的屏障。
This study employed isolated guinea-pig tracheal tube preparations in order to examine effects of increases in hydrostatic pressure on the movement of macromolecular solutes (fluorescein isothiocyanate-conjugated dextran; FITC-D, MW 70 kD; kept either in serosal or mucosal bathing fluids) across the mucosa. An asymmetry of the mucosal barrier was demonstrated by the finding that under baseline zero-pressure difference conditions luminal entry of serosal FITC-D was greater than serosal entry of luminal FITC-D. Furthermore, an increased serosal pressure (5 cm H2O) moved significant amounts of serosal FITC-D into the lumen, whereas a corresponding pressure applied on the luminal side only marginally increased mucosal crossing of luminal FITC-D. By raising the luminal pressure to 10 and 20 cm H2O (which may be used as positive end-expiratory pressures (PEEP) in vivo in patients) mucosal penetration of luminal FITC-D was as marked as that induced in the opposite direction by the low (5 cm H2O) serosal pressure increase. Another aspect of the asymmetry of the airway mucosal barrier was evident from experiments examining the effect of a serosal pressure increase on mucosal penetration of luminal FITC-D. Neither during nor after the period of sustained serosal pressure increase was luminal FITC-D crossing the mucosa to a greater extent than under baseline zero-pressure conditions. This finding agrees with in-vivo data demonstrating that plasma exudation into the airway lumen may not be associated with an increased absorption of luminal solutes. The present results support the possibility that a plasma exudate itself creates pathways for its luminal entry by the following mechanism: by increasing the subepithelial hydrostatic pressure slightly a lateral compressive effect on epithelial cells is achieved, whereby apical tight junctions also separate to let through a bulk flow of different-sized plasma solutes; this is a distinct increase in outward permeability on the epithelium and when the pressure is reduced the tight junctions reassemble; hence, both during and after the exudation process the mucosa maintains its integrity as a barrier to luminal solutes.