Hsueh W, Gonzalez-Crussi F, Arroyave J L
Am J Pathol. 1986 Feb;122(2):231-9.
The authors have previously reported a model of ischemic bowel necrosis produced in the rat by synthetic platelet-activating factor (PAF) or a combination of PAF and bacterial endotoxin. Because rat platelets are refractory to PAF and thromboemboli were not found in the mesenteric or intestinal microvasculature, they suspected that secondary mediators were involved in the pathogenesis of bowel necrosis. They have found the following lipoxygenase products of arachidonic acid, especially leukotrienes (LT), probably played an important role in the pathogenesis of bowel necrosis, because diethylcarbamazine (an inhibitor for LTA synthesis) and FPL55712 (LT antagonist) ameliorated, and at times completely prevented, the lesions. NDGA (a nonspecific lipoxygenase inhibitor) was less effective, probably because of its additional effect on cyclooxygenase inhibition. Verapamil, a calcium channel blocker, ameliorated the disease. Thromboxane A2, a potent vasoconstrictor, was probably not responsible for the ischemia of the gastrointestinal tract. This is suggested by the ineffectiveness of OKY-046 in preventing bowel necrosis. Prostaglandin (PG) E1 infusion often prevented the bowel necrosis, which suggested beneficial effects of vasodilating PGs, probably released as a defense mechanisms. Indomethacin aggravated the disease, probably by inhibiting PG release and shifting the metabolic pathway toward the lipoxygenase pathway. Antihistamine and antiserotonin had no effect, which suggested that these mediators were not involved in the pathogenesis of bowel necrosis. Shock produced by PAF was probably not the only cause of bowel necrosis, because reversal of the hypotension did not always prevent the development of bowel necrosis. Hemoconcentration (increased vasopermeability) and leukopenia induced by PAF did not correlate with the development or severity of bowel necrosis.
作者此前曾报道过一种通过合成血小板激活因子（PAF）或PAF与细菌内毒素联合作用在大鼠体内产生缺血性肠坏死的模型。由于大鼠血小板对PAF不敏感，且在肠系膜或肠道微血管中未发现血栓栓塞，他们怀疑继发性介质参与了肠坏死的发病机制。他们发现花生四烯酸的以下脂氧合酶产物，尤其是白三烯（LT），可能在肠坏死的发病机制中起重要作用，因为乙胺嗪（LTA合成抑制剂）和FPL55712（LT拮抗剂）可改善病变，有时甚至能完全预防病变。NDGA（一种非特异性脂氧合酶抑制剂）效果较差，可能是因为它对环氧化酶也有抑制作用。钙通道阻滞剂维拉帕米可改善病情。血栓素A2是一种强效血管收缩剂，可能与胃肠道缺血无关。OKY - 046预防肠坏死无效表明了这一点。输注前列腺素（PG）E1通常可预防肠坏死，这表明血管舒张性PG可能作为一种防御机制释放，具有有益作用。吲哚美辛会加重病情，可能是因为它抑制了PG释放，并使代谢途径转向脂氧合酶途径。抗组胺药和抗5 - 羟色胺药无效，这表明这些介质不参与肠坏死的发病机制。PAF引起的休克可能不是肠坏死的唯一原因，因为血压逆转并不总是能预防肠坏死的发生。PAF诱导的血液浓缩（血管通透性增加）和白细胞减少与肠坏死的发生或严重程度无关。
