Harada N, Okajima K, Murakami K, Isobe H, Liu W
Department of Laboratory Medicine, Kumamoto University School of Medicine, Honjo, Japan.
Prostaglandins Other Lipid Mediat. 1999 Jul;57(5-6):291-303. doi: 10.1016/s0090-6980(98)00077-x.
We investigated whether, in rats, gastric prostacyclin (PGI2) prevented gastric mucosal injury that was induced by water-immersion restraint stress by inhibiting leukocyte activation. Gastric levels of 6-keto-PGF1alpha, a stable metabolite of PGI2, increased transiently 30 min after stress, followed by a decrease to below the baseline 6-8 h after stress. Gastric mucosal blood flow decreased to approximately 40% of the baseline level 8 h after stress. Myeloperoxidase activity was significantly increased 8 h after stress. Treatment with indomethacin before stress inhibited the increase in 6-keto-PGF1alpha levels and markedly reduced mucosal blood flow. It also markedly increased leukocyte accumulation and mucosal lesion formation. Iloprost, a stable PGI2 analog, inhibited the indomethacin-induced decrease in mucosal blood flow, mucosal lesion exacerbation, and increase in leukocyte accumulation. Nitrogen mustard-induced leukocytopenia inhibited the indomethacin-associated lesion exacerbation and the increase in leukocyte accumulation, but not the decreases in mucosal blood flow. These observations indicate that gastric PGI2 decreases gastric mucosal lesion formation primarily by inhibiting leukocyte accumulation.
我们研究了在大鼠中，胃前列腺素I2（PGI2）是否通过抑制白细胞活化来预防水浸束缚应激诱导的胃黏膜损伤。PGI2的稳定代谢产物6-酮-前列腺素F1α的胃内水平在应激后30分钟短暂升高，随后在应激后6 - 8小时降至基线以下。应激后8小时，胃黏膜血流量降至基线水平的约40%。应激后8小时，髓过氧化物酶活性显著增加。应激前用吲哚美辛治疗可抑制6-酮-前列腺素F1α水平的升高，并显著降低黏膜血流量。它还显著增加白细胞聚集和黏膜损伤形成。稳定的PGI2类似物伊洛前列素可抑制吲哚美辛诱导的黏膜血流量减少、黏膜损伤加重以及白细胞聚集增加。氮芥诱导的白细胞减少可抑制吲哚美辛相关的损伤加重和白细胞聚集增加，但不能抑制黏膜血流量的减少。这些观察结果表明，胃PGI2主要通过抑制白细胞聚集来减少胃黏膜损伤的形成。
