Orth Teresa, Allen Julie A, Wood John G, Gonzalez Norberto C
Univ. of Kansas Medical Center, Kansas City, KS 66160, USA.
J Appl Physiol (1985). 2005 Jul;99(1):290-7. doi: 10.1152/japplphysiol.00932.2004. Epub 2005 Mar 3.
Systemic hypoxia results in rapid increases in leukocyte-endothelial adherence (LEA) and emigration, vascular permeability, and mast cell activation in several microcirculations. Observations in cremaster muscle suggest that this response is initiated by a mediator released from a distant site (Dix R, Orth T, Allen JA, Wood JG, and Gonzalez NC. J Appl Physiol 95: 2495-2502, 2003). The present experiments in rat cremaster muscle tested the hypothesis that, if a circulating mediator triggers hypoxia-induced inflammation, then plasma from hypoxic rats should elicit LEA in normoxic cremaster venules. Plasma from conscious donor rats breathing 10% O2-90% N2 for 5 min was applied topically to the cremaster of normoxic anesthetized rats. In this and all other groups described below, the donor plasma had attained normoxic PO2 when applied to the cremaster. LEA (leukocytes/100-microm venule) increased from 2.7 +/- 0.8 to 12.3 +/- 2.4, and venular shear rate and arteriolar diameter decreased to 79 +/- 9% (P < 0.05, n = 6) and 77 +/- 5% of control (P < 0.05, n = 5), respectively, 10 min after application of plasma from hypoxic donors. The decrease in venular shear rate was exclusively due to a reduction of venular blood flow, secondary to the upstream arteriolar vasoconstriction. Plasma from normoxic donors had no effects. Plasma from blood equilibrated in vitro for 5 min with 5% CO2-95% N2 did not alter LEA or shear rate of normoxic cremasters, suggesting that the putative mediator does not originate in blood cells. The effects of plasma from hypoxic rats persisted when the donors were pretreated with the mast cell stabilizer cromolyn, which prevents hypoxia-induced LEA. This suggests that the effects of hypoxic plasma are not due to inflammatory mediators released by adherent leukocytes in the donor rat. There was a positive correlation between LEA and mast cell degranulation observed histologically. These results support the idea that systemic hypoxia produces the release of a substance transported by the circulation that initiates the microvascular inflammation.
全身性缺氧会导致多种微循环中白细胞与内皮细胞的黏附（LEA）及移出、血管通透性和肥大细胞活化迅速增加。在提睾肌中的观察表明，这种反应是由远处部位释放的一种介质引发的（迪克斯R、奥思T、艾伦JA、伍德JG和冈萨雷斯NC。《应用生理学杂志》95：2495 - 2502，2003年）。本研究在大鼠提睾肌中进行实验，以验证以下假设：如果一种循环介质触发缺氧诱导的炎症，那么缺氧大鼠的血浆应能在常氧的提睾肌微静脉中引发LEA。将清醒的供体大鼠呼吸10% O₂ - 90% N₂ 5分钟后的血浆局部应用于常氧麻醉大鼠的提睾肌。在本实验以及下文所述的所有其他组中，当将供体血浆应用于提睾肌时，其已达到常氧的氧分压。应用缺氧供体的血浆10分钟后，LEA（白细胞数/100微米微静脉）从2.7±0.8增加到12.3±2.4，微静脉切变率和小动脉直径分别降至对照值的79±9%（P < 0.05，n = 6）和77±5%（P < 0.05，n = 5）。微静脉切变率的降低完全是由于上游小动脉血管收缩导致微静脉血流减少所致。常氧供体的血浆无此作用。在体外与5% CO₂ - 95% N₂平衡5分钟的血液的血浆不会改变常氧提睾肌的LEA或切变率，这表明假定的介质并非源自血细胞。当供体用肥大细胞稳定剂色甘酸预处理时，缺氧大鼠血浆的作用仍然存在，色甘酸可防止缺氧诱导的LEA。这表明缺氧血浆的作用并非由于供体大鼠中黏附白细胞释放的炎症介质所致。组织学观察发现LEA与肥大细胞脱颗粒之间存在正相关。这些结果支持了全身性缺氧会导致循环中运输的一种物质释放，从而引发微血管炎症这一观点。
