LeDuc L E, Su K C, Guth E, Reedy T, Guth P H
Department of Medicine, Harbor UCLA Medical Center, Torrance.
Dig Dis Sci. 1993 Feb;38(2):289-94. doi: 10.1007/BF01307546.
Both cyclooxygenase products, such as prostaglandin (PG) E2, and lipoxygenase products, such as leukotriene (LT) B4, are increased in colitis and have potent proinflammatory actions. We studied effects of specific inhibitors of cyclooxygenase and 5-lipoxygenase on the healing of acetic acid colitis in rats. Acetic acid colitis was induced 24 hr before enzyme inhibition began. Four days after induction of colitis, the area of gross colonic mucosal damage was determined by image analysis. Eicosanoid content in the intestinal lumen was quantitated by radioimmunoassay following chromatographic purification. Under these conditions, indomethacin significantly retarded the healing of colonic lesions and inhibited PGE2 by > 90% compared to placebo-treated colitis rats. AA861 had no effect on the healing of lesions, although > 75% inhibition of leukotriene synthesis was demonstrated. These results suggest that inhibition of endogenous colonic prostaglandins can impair healing mechanisms in acute colitis even after inflammation has developed. In contrast, inhibition of leukotriene synthesis did not affect healing.
环氧化酶产物，如前列腺素（PG）E2，以及脂氧化酶产物，如白三烯（LT）B4，在结肠炎中均会增加，并具有强大的促炎作用。我们研究了环氧化酶和5-脂氧化酶的特异性抑制剂对大鼠乙酸结肠炎愈合的影响。在开始酶抑制作用前24小时诱发大鼠乙酸结肠炎。诱发结肠炎4天后，通过图像分析确定结肠大体黏膜损伤面积。在色谱纯化后，通过放射免疫分析法对肠腔中的类花生酸含量进行定量。在这些条件下，与安慰剂治疗的结肠炎大鼠相比，吲哚美辛显著延缓了结肠损伤的愈合，并抑制PGE2超过90%。尽管已证实AA861对白三烯合成的抑制率超过75%，但其对损伤的愈合没有影响。这些结果表明，即使在炎症已经发展之后，抑制内源性结肠前列腺素也会损害急性结肠炎的愈合机制。相比之下，抑制白三烯合成并不影响愈合。
