Ko J K, Ma J J, Chow J Y, Ma L, Cho C H
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, China.
Free Radic Biol Med. 1998 Apr;24(6):1007-14. doi: 10.1016/s0891-5849(97)00428-0.
The effects of 5-hydroxytryptamine (5-HT) on ethanol-induced gastric mucosal damage and on epithelial and vascular integrity were investigated. Male Sprague-Dawley rats were administered with 5-HT (5 or 10 mg/kg, IP) 30 min prior to the challenge with ethanol (40% v/v, 10 ml/kg, PO). 5-HT dose dependently aggravated ethanol-induced injury in the gastric mucosa. Both xanthine oxidase (XO) and myeloperoxidase (MPO) activities in the mucosa were significantly increased with the high dose of 5-HT, which also potentiated the elevation of these enzyme activities by ethanol. However, the mucosal superoxide dismutase activity was left unaltered. In neutropenic (antineutrophil serum-treated) animals, the ethanol-induced gastric mucosal injury was significantly ameliorated, with or without the pretreatment of 5-HT (10 mg/kg). In addition, the effect of 5-HT on the activity of MPO, but not of XO, was also attenuated in these animals. In the ex vivo gastric chamber study on pentobarbital-anesthetized animals, volume of gastric secretion was significantly decreased in the 5-HT-treated groups, with further reduction after ethanol incubation. Transmucosal potential difference (PD) was significantly reduced in 5-HT-treated rats, which also potentiated the ethanol-induced drop in PD. Nevertheless, 5-HT dose dependently increased mucosal vascular permeability and further enhanced during ethanol incubation. These findings suggest that 5-HT adversely affects the defense mechanisms of the gastric mucosa by reducing the secretory function of the mucosal cells and to weaken the epithelial and vascular integrity. Neutrophil activation appears to be responsible for the detrimental effects of 5-HT partly through the elevation in MPO activity. The increase in mucosal XO activity by 5-HT may induce free radical production and possibly modulate the ulcerogenic processes.
研究了5-羟色胺（5-HT）对乙醇诱导的胃黏膜损伤以及上皮和血管完整性的影响。在给雄性Sprague-Dawley大鼠灌胃乙醇（40% v/v，10 ml/kg）前30分钟，腹腔注射5-HT（5或10 mg/kg）。5-HT剂量依赖性地加重乙醇诱导的胃黏膜损伤。高剂量5-HT使黏膜中的黄嘌呤氧化酶（XO）和髓过氧化物酶（MPO）活性显著增加，同时也增强了乙醇对这些酶活性的升高作用。然而，黏膜超氧化物歧化酶活性未发生改变。在中性粒细胞减少（抗中性粒细胞血清处理）的动物中，无论是否进行5-HT（10 mg/kg）预处理，乙醇诱导的胃黏膜损伤均显著减轻。此外，在这些动物中，5-HT对MPO活性的影响减弱，但对XO活性的影响未减弱。在对戊巴比妥麻醉动物进行的离体胃腔研究中，5-HT处理组的胃分泌量显著减少，乙醇孵育后进一步降低。5-HT处理的大鼠跨黏膜电位差（PD）显著降低，同时也增强了乙醇诱导的PD下降。然而，5-HT剂量依赖性地增加黏膜血管通透性，乙醇孵育期间进一步增强。这些发现表明，5-HT通过降低黏膜细胞的分泌功能以及削弱上皮和血管完整性，对胃黏膜的防御机制产生不利影响。中性粒细胞激活似乎部分通过MPO活性升高导致5-HT的有害作用。5-HT使黏膜XO活性增加可能诱导自由基产生并可能调节溃疡形成过程。
