Lee H C, Hardman J M, Lum B K
Department of Pharmacology, John A. Burns School of Medicine, University of Hawaii, Honolulu 96822.
Life Sci. 1989;45(10):877-83. doi: 10.1016/0024-3205(89)90201-4.
We previously reported that calcium entry blockers (CEBs) protected against endotoxin-induced mortality in rats. In this investigation, the i.v. injection of endotoxin (ETX) in control awake male Wistar rats was found to produce pathophysiological changes indicative of disseminated intravascular coagulation (DIC). The latter included increased serum fibrin (ogen) degradation products (FDP), decreased plasma fibrinogen, reduced blood platelet count as well as microscopic findings of fibrin microthrombi in small blood vessels of visceral organs. Gross pathological examination revealed pronounced hemorrhagic congestion of the gastrointestinal tract and petechial and ecchymotic hemorrhages in other visceral organs. Pretreatment with the CEBs, nilvadipine (FR 34235) and nitrendipine, inhibited the elevation in serum FDP and decrease in plasma fibrinogen but did not prevent the thrombocytopenia produced by ETX. The gross pathological manifestations of DIC were also inhibited by pretreatment with the CEBs. The results suggest that the protective effect of CEBs against endotoxin-induced mortality in rats may be related to inhibition of DIC caused by the lipopolysaccharide.
我们之前报道过，钙通道阻滞剂（CEBs）可保护大鼠免受内毒素诱导的死亡。在本研究中，发现给清醒的雄性Wistar对照大鼠静脉注射内毒素（ETX）会产生提示弥散性血管内凝血（DIC）的病理生理变化。后者包括血清纤维蛋白（原）降解产物（FDP）增加、血浆纤维蛋白原降低、血小板计数减少以及在内脏器官小血管中出现纤维蛋白微血栓的微观表现。大体病理检查显示胃肠道有明显的出血性充血，其他内脏器官有瘀点和瘀斑出血。用CEBs尼伐地平（FR 34235）和尼群地平预处理可抑制血清FDP升高和血浆纤维蛋白原降低，但不能预防ETX所致的血小板减少。用CEBs预处理也可抑制DIC的大体病理表现。结果表明，CEBs对大鼠内毒素诱导死亡的保护作用可能与抑制脂多糖引起的DIC有关。
