及酒精性肠粘膜损伤药物干预ppt课件.pptVIP

NSAID及酒精性肠粘膜损伤药物干预研究 技术目标 拟通过对塞来昔布和酒精对小肠粘膜的损伤及雷贝拉唑、瑞巴派特、米索前列醇、谷氨酰胺四种药物的干预效应进行研究，阐明NSAID引起肠道损伤的发病机制，探讨不同药物干预对NSAID相关小肠损伤的影响，达到在有效保护胃粘膜、预防胃溃疡的同时积极防治小肠疾病、减轻肠道炎症、减少NSAID相关胃肠不良事件的发生。 药物 吲哚美辛（INN名称：Indometacin 氟比洛芬 flurbiprofen; 双氯芬酸 diclofenac Celecoxib mucosa injury塞来昔布 alcohol酒精 rabeprazole雷贝拉唑 Rebamipide瑞巴派特 misoprostol米索前列醇 glutamine谷氨酰胺 The gastric ulcerogenic response was examined as described previously [25], with some modifications. Mice fasted for 18 h were intravenously administered indomethacin in PBS via the tail vein and 1 h later, orally administered celecoxib in 1% methylcel- lulose in a volume of 10 ml/kg. In some experiments, mice were orally administered rebamipide in 0.5% carboxymethylcellulose in a volume of 10 ml/kg 1 h before the administration of indometha- cin. Eight hours after the administration of celecoxib, the animals were sacrificed, after which their stomachs were removed and the areas of the gastric mucosal lesions were measured by an observer unaware of the treatment they had received. Calculation of the scores involved measuring the area of all the lesions in square millimetres and summing the values to give an overall gastric lesion index. The gastric PGE 2 level was determined by EIA according to the manufacturer’s instructions. celecoxib (10 mg/kg) The effective daily dose of celecoxib in rats is 5–30 mg/kg body weight (Herbenick et al., 2008). In a similar study design, other workers have shown that the lowest dose of celecoxib that could inhibit PGE 2 in gastric mucosa was 30 mg/kg body weight (Berenguer et al., 2004). Therefore, in the present study a dose of 30 mg/kg body weight of celecoxib was selected to evaluate its effect on gastric mucosa. Experimental time of 6 h was selected as it has been shown that damage induced by the assayed drugs peak 6 h after oral administration (Villegas et al., 2002; Sanchez et al., 2002). in 0.1% methylcellulose (MC) solution, and in 0.5% MC solution for rats. celecoxib (Pfizer), 30 and 100 mg