摘要
目的 环氧合酶 (COX)是合成前列腺素 (PGs)的关键酶 ,传统的非甾体抗炎药 (NSAIDs)抑制COX 1和COX 2活性 ,引起严重的胃肠道不良反应。特异性COX 2抑制剂有望成为不引起胃损伤的新型NSAIDs。本研究探讨特异性和非特异性COX 2抑制剂对盐酸诱导大鼠胃黏膜损伤愈合的影响。方法 雄性SD大鼠胃内给予 0 .6mol/LHCl1ml,Westernblot和免疫组化法分析胃黏膜COX 1和COX 2表达。盐酸灌胃后 10min ,实验组胃内给予NS 3980 .4、4、4 0mg/kg和吲哚美辛 4 0mg/kg ,对照组胃内给予 1%阿拉伯树胶 (AG) 5ml/kg。盐酸灌胃前和灌胃后 1、3、6、12、2 4及 4 8h分别处死大鼠 ,剖腹取胃 ,观察各组动物损伤指数 (LI)及光镜下的胃黏膜病理学改变。结果 盐酸灌胃后COX 2在表层上皮细胞和颈黏液细胞表达显著增加 ,NS 398和吲哚美辛均延迟胃黏膜损伤的愈合。盐酸灌胃后 12h ,NS 398组 (4和 4 0mg/kg)及吲哚美辛组的LI分别为 (1.4 2± 0 .2 3) % ,(1.4 2± 0 .2 9) %和 (1.6 2± 0 .4 4 ) % ,明显高于对照组的 (0 .5 8± 0 .2 4 ) % (P <0 .0 5 )。结论 特异性和非特异性COX 2抑制剂延迟大鼠胃损伤后的愈合 ,提示COX
Objective Cyclooxygenase (COX), the key enzyme for synthesis of prostaglandins (PGs), exists in two isoforms (COX 1 and COX 2). Conventional non steroidal anti inflammatory drugs (NSAIDs) inhibit both COX 1 and COX 2 activities and induce serious gastrointestinal side effects. Specific COX 2 inhibitors are expected to cause fewer gastric side effects. The aim of this study was to investigate the effects of specific and non specific COX 2 inhibitors on gastric wound healing following acid induced injury. Methods Male Sprague Dawley rats were given 1 ml of 0.6 mol/L hydrochloric acid (HCl) into the stomach. Levels of COX 1 and COX 2 in gastric mucosa were analyzed using western blotting and immunohistochemical staining. At 10 minutes after the administration of the acid, the animals were given 0.4, 4 and 40 mg/kg of NS 398 (NS) or 40 mg/kg of indomethacin (IM). Control group was given 1% arabic gum (AG) in a volume of 5 ml/kg. The rats were sacrificed and laparotomized before and at 1, 3, 6, 12, 24, 48 h after acid administration. Lesion index (LI) was measured and morphological changes of gastric mucosa were assessed under light microscopy. Results Expression of COX 2 was enhanced mainly in surface epithelial cells and neck cells after HCl administration. NS and IM delayed the healing of gastric injury. At 12 h after acid administration, LI was (1.42 ± 0.23)% and (1.42 ± 0.29)% in the groups treated with 4 and 40 mg/kg of NS respectively, and (1.62 ± 0.44)% in the group treated with 40 mg/kg of IM, which was significantly higher than that in control group [(0.58±0.24)%, P <0.05 ]. Conclusions Both specific and non specific COX 2 inhibitors delay gastric wound healing and the expression of COX 2 plays an important role in gastric mucosal regeneration.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2003年第2期84-87,共4页
Chinese Journal of Digestion
