Miller T A, Gum E T, Guinn E J, Henagan J M
Dig Dis Sci. 1982 Sep;27(9):776-81. doi: 10.1007/BF01391369.
Fasted rats were given either 16,16-dimethyl-PGE2 (dmPGE2) (1 microgram/kg) or normal saline subcutaneously followed by the oral administration of 1 ml of 100% ethanol or saline 30 min later. At 1, 3, 6, and 24 hr later, animals were sacrificed, their stomachs examined for necrotic ulcerations, and the incorporation of [3H]thymidine into DNA as well as tissue levels of DNA, RNA, and protein content of glandular mucosa determined. Compared with control animals, severe ulcerations of 70-80% of the glandular mucosa were observed in rats given 100% ethanol at all time periods. Accompanying these ulcerations were marked depressions in tissue levels of DNA and RNA at 1, 3, 6, and 24 hr after exposure to ethanol, and protein at 1, 3, and 6 hr following ethanol. In rats pretreated with dmPGE2 before ethanol administration, these alterations in tissue levels of DNA, RNA, and protein were prevented as were ulcerations of the glandular stomach at each time period. Synthesis of mucosal DNA was not significantly different from control rats in any of the groups studied. It is concluded that (1) gastric mucosal damage by alcohol is associated with a decrease in tissue levels of DNA, RNA, and protein; (2) dmPGE2 maintains normal tissue levels of DNA, RNA, and protein by preventing the shedding of mucosal cells by alcohol; and (3) the ability of dmPGE2 to prevent gastric damage by alcohol is not mediated through stimulation of DNA synthesis.
禁食的大鼠皮下注射16,16 - 二甲基前列腺素E2(dmPGE2)(1微克/千克)或生理盐水,30分钟后口服1毫升100%乙醇或生理盐水。1、3、6和24小时后,处死动物,检查其胃部有无坏死性溃疡,并测定[3H]胸腺嘧啶核苷掺入DNA的情况以及腺黏膜的DNA、RNA组织水平和蛋白质含量。与对照动物相比,在所有时间段给予100%乙醇的大鼠中,观察到70 - 80%的腺黏膜出现严重溃疡。伴随这些溃疡,在接触乙醇后1、3、6和24小时,DNA和RNA的组织水平显著降低,在乙醇处理后1、3和6小时蛋白质水平降低。在乙醇给药前用dmPGE2预处理的大鼠中,DNA、RNA和蛋白质的组织水平变化以及腺胃在每个时间段的溃疡均得到预防。在所研究的任何组中,黏膜DNA的合成与对照大鼠无显著差异。得出以下结论:(1)酒精对胃黏膜的损伤与DNA、RNA和蛋白质的组织水平降低有关;(2)dmPGE2通过防止酒精导致的黏膜细胞脱落来维持DNA、RNA和蛋白质的正常组织水平;(3)dmPGE2预防酒精所致胃损伤的能力不是通过刺激DNA合成介导的。