Schneidkraut M J, Carlson R W
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan.
J Pharmacol Exp Ther. 1990 Jun;253(3):1171-6.
This study determined whether a sepsis-associated increase in cyclooxygenase products altered the pulmonary vascular response to the thromboxane A2 mimic, 9,11-dideoxy-11a,9a-epoxymethano-prostaglandin F2 alpha (U46619). Rats were anesthetized (50 mg/kg of sodium pentobarbital i.p.), and sepsis was induced by cecal ligation and puncture. Four hours later, pulmonary effluent immunoreactive thromboxane (iTXB2) levels were significantly increased (156.8%) and pulmonary vascular reactivity to U46619 (50-200 ng) was significantly (P less than .05) decreased compared to lungs from nonseptic controls. This decreased vascular reactivity was not seen in lungs from cecally ligated rats challenged with angiotensin II (5-200 ng). Sham surgery did not alter pulmonary iTXB2 synthesis nor did it result in a depressed vascular response to U46619. Rats pretreated with ibuprofen (15 mg/kg i.v.) did not show the sepsis-associated increase in iTXB2 levels nor was a decrease in pulmonary vascular reactivity to U46619 observed. These data indicate that a sepsis-associated increase in TXA2 and/or other cyclooxygenase products can alter the pulmonary vascular response to the TXA2 mimic, U46619.
本研究确定了脓毒症相关的环氧化酶产物增加是否会改变肺血管对血栓素A2类似物9,11-二脱氧-11α,9α-环氧甲撑-前列腺素F2α（U46619）的反应。大鼠经腹腔注射50mg/kg戊巴比妥钠麻醉，通过盲肠结扎和穿刺诱导脓毒症。4小时后，与非脓毒症对照大鼠的肺相比，肺流出液中免疫反应性血栓素（iTXB2）水平显著升高（156.8%），而肺血管对U46619（50-200ng）的反应性显著降低（P<0.05）。在用血管紧张素II（5-200ng）刺激的盲肠结扎大鼠的肺中未观察到这种血管反应性降低。假手术未改变肺iTXB2合成，也未导致对U46619的血管反应性降低。用布洛芬（15mg/kg静脉注射）预处理的大鼠未表现出脓毒症相关的iTXB2水平升高，也未观察到肺血管对U46619的反应性降低。这些数据表明，脓毒症相关的TXA2和/或其他环氧化酶产物增加可改变肺血管对TXA2类似物U46619的反应。
