Little T M, Butler B D
Department of Anesthesiology, University of Texas Medical School, Houston 77030, USA.
Undersea Hyperb Med. 1997 Sep;24(3):185-91.
Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.
减压诱导的静脉气泡形成与中性粒细胞计数增加、内皮细胞损伤、血管活性类二十烷酸的释放以及血管膜通透性增加有关。这些作用可能是炎症反应和水肿形成的原因。在各种肺损伤模型中，增加细胞内cAMP已被证明可减少类二十烷酸的产生和水肿形成。在用生理盐水（对照组）或二丁酰cAMP（DBcAMP，一种cAMP类似物）预处理的减压大鼠中，评估了减压诱导的炎症反应的减轻情况。预处理后，大鼠分别暴露于616 kPa 120分钟或683 kPa 60分钟。在生理盐水对照组（683 kPa）中观察到的血管外肺水比率（肺水肿）、支气管肺泡灌洗和胸膜蛋白的增加，在DBcAMP治疗组中并不明显。DBcAMP预处理对白细胞计数和支气管肺泡灌洗中中性粒细胞百分比也有影响。在683 kPa生理盐水对照减压暴露下，血栓素B2、11-脱氢血栓素B2和白三烯E4的尿水平显著增加。DBcAMP减少了减压诱导的尿中白三烯E4的产生。在683-kPa暴露组中，血浆血栓素B2、11-脱氢血栓素B2和白三烯E4水平升高。DBcAMP治疗并未影响这些变化。在683 kPa暴露下，支气管肺泡灌洗中的11-脱氢血栓素B2和白三烯E4水平升高，而DBcAMP治疗使其降低。我们的结果表明，DBcAMP有能力减少类二十烷酸的产生，并限制经历减压病的大鼠的膜通透性和随后的水肿形成。
