Halushka P V, Wise W C, Cook J A
Am J Med. 1983 Jun 14;74(6A):91-6. doi: 10.1016/0002-9343(83)90535-1.
Endotoxic shock is associated with increased metabolism of arachidonic acid into thromboxanes and prostaglandins. This study assessed the effects of varied doses of aspirin, an inhibitor of arachidonic acid metabolism, on Salmonella enteritidis endotoxin-induced mortality, plasma levels of arachidonate metabolites, and other pathophysiologic sequelae in Long-Evans rats. Aspirin in doses of 3.75, 15, and 30 mg/kg given 30 minutes prior to endotoxin challenge significantly (p less than 0.01) improved 24-hour survival rates from 11 percent to approximately 65 percent, but 100 mg/kg afforded no protection. Pretreatment with aspirin (15 or 100 mg/kg) 30 minutes prior to endotoxin also significantly (p less than 0.001) decreased the endotoxin-induced elevations in plasma levels of immunoreactive thromboxane B2, a stable metabolite of thromboxane A2, and immunoreactive 6-keto prostaglandin F1 alpha, a stable metabolite of prostacyclin. Aspirin doses of 15 or 100 mg/kg given 24 hours prior to challenge with endotoxin significantly improved 24-hour survival rates from 17 percent to 42 percent (p less than 0.01) and 44 percent (p less than 0.005), respectively. Pretreatment with an aspirin dose of 15 mg/kg 24 hours prior to challenge with endotoxin significantly (p less than 0.05) inhibited thrombin-induced immunoreactive thromboxane B2 synthesis in platelet-rich plasma (in vitro) and endotoxin-induced immunoreactive 6-keto-prostaglandin F1 alpha and immunoreactive thromboxane B2 synthesis by rat peritoneal macrophages. Although 24-hour pretreatment with aspirin (15 or 100 mg/kg) significantly (p less than 0.001) reduced endotoxin-induced elevations in immunoreactive thromboxane B2, only the 100 mg/kg dose significantly lowered plasma levels of immunoreactive 6-keto prostaglandin F1 alpha. These observations are consistent with the notion that the beneficial effects of aspirin seen in experimental endotoxic shock may be mediated, in part, via inhibition of arachidonic acid metabolism.
内毒素休克与花生四烯酸代谢为血栓素和前列腺素的增加有关。本研究评估了不同剂量的阿司匹林（一种花生四烯酸代谢抑制剂）对肠炎沙门氏菌内毒素诱导的死亡率、花生四烯酸代谢产物的血浆水平以及长-伊文斯大鼠其他病理生理后遗症的影响。在内毒素攻击前30分钟给予3.75、15和30mg/kg剂量的阿司匹林显著（p小于0.01）提高了24小时生存率，从11%提高到约65%，但100mg/kg剂量没有提供保护作用。在内毒素攻击前30分钟用阿司匹林（15或100mg/kg）预处理也显著（p小于0.001）降低了内毒素诱导的血浆中免疫反应性血栓素B2（血栓素A2的稳定代谢产物）和免疫反应性6-酮-前列腺素F1α（前列环素的稳定代谢产物）水平的升高。在内毒素攻击前24小时给予15或100mg/kg剂量的阿司匹林显著提高了24小时生存率，分别从17%提高到42%（p小于0.01）和44%（p小于0.005）。在内毒素攻击前24小时用15mg/kg剂量的阿司匹林预处理显著（p小于0.05）抑制了凝血酶诱导的富含血小板血浆中免疫反应性血栓素B2的合成（体外）以及内毒素诱导的大鼠腹腔巨噬细胞中免疫反应性6-酮-前列腺素F1α和免疫反应性血栓素B2的合成。尽管用阿司匹林（15或100mg/kg）进行24小时预处理显著（p小于0.001）降低了内毒素诱导的免疫反应性血栓素B2水平的升高，但只有100mg/kg剂量显著降低了血浆中免疫反应性6-酮-前列腺素F1α的水平。这些观察结果与以下观点一致，即在实验性内毒素休克中看到的阿司匹林的有益作用可能部分是通过抑制花生四烯酸代谢介导的。
