吲哚美辛对乙酸诱导大鼠胃溃疡形成和愈合的影响

Effects of Indomethacin on Formation and Healing of Acetic Acid-Induced Gastric Ulcer in Rats

目的 利用乙酸诱导大鼠胃溃疡模型研究吲哚美辛对化学诱导胃溃疡形成和愈合的影响 ,探讨其可能机制。方法 雄性SD大鼠 ,体重 16 0～ 180 g。分两组 ,即单纯乙酸诱导胃溃疡作为对照组和乙酸诱导胃溃疡加吲哚美辛处理组 ,各时间点每组均 8只。乙酸诱导胃溃疡后 1、3和 7d用RT PCR和Westernblotting分别检测胃黏膜中环氧合酶 (COX)和诱导型一氧化氮合酶 (iNOS)的表达。用ELISA测定胃黏膜中PGE2 量反映COX活性。同时研究吲哚美辛对iNOS表达、活性及胃黏膜损伤的影响 ,以溃疡面积来评估胃黏膜损伤程度。结果 RT PCR结果显示乙酸诱导大鼠胃溃疡后 ,COX2 mRNA表达明显升高 ;以溃疡基底部为明显 ,3d最高 ,7d下降。胃黏膜PGE2 合成也明显增高。吲哚美辛能抑制胃黏膜PGE2 合成 ,处理组溃疡面积 1d时为 (5 2 .6± 6 .1)mm2 ,小于对照组的 (71.8± 5 .8)mm2 (P <0 .0 5 ) ,且周围充血水肿较轻 ;3d时两组溃疡大小无差异 ,但吲哚美辛处理组溃疡基底部厚度为 (11± 0 .5 )mm ,薄于对照组的 (2 0± 0 .8)mm(P <0 .0 1) ;7d时吲哚美辛组溃疡面积为 (35 .4± 3.5 )mm2 ,大于对照组的 (2 4.8± 3.2 )mm2 (P <0 .0 5 )。此外吲哚美辛能降低胃黏膜iNOS的表达及活性。结论 吲哚美辛能减轻大鼠溃疡形成初期炎症反应 。

Purpose: To investigate the possible role of indomethacin in formation and healing of acetic acid-induced gastric ulcer in rats. Methods: Male Sprague Dawley rats weighing 160-180 g were used in the experiments. Rats were divided into two groups (n = 8 in each group), gastric ulcer induced by acetic acid as control group and acetic acid-induced ulcer with indomethacin as treatment group. The expression of cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS) mRNA and protein were determined at different time points (1,3 and 7 d) after acetic acid induced gastric ulcer in rats by RT-PCR and western blotting, respectively. Prostaglandin E2 (PGE2) was also determined in the gastric mucosa by ELISA. The severity of ulcer was assessed by ulcer area. The effect of indomethacin on the expression and activity of iNOS were also investigated. Results: COX2 gene expression was markedly increased and PGE2 production was elevated in gastric mucosa after ulcer induction. The increased PGE2 production was inhibited by indomethacin. The ulcer area in rats with indomethacin treatment group 1 day after ulcer induction was significantly lower than that of corresponding control, there was no significantly difference between indomethacin treatment group and control group in the ulcer area 3 days after ulceration. However, the ulcer area of indomethacin treatment group was significantly higher than control group in 7 days after ulcer induction. Along with the severity changes of mucosal lesion, the iNOS expression and activity decreased markedly in indomethacin group. Conclusions: The inhibition of COX activity by indomethacin may affect acetic acid induced gastric ulcer formation by decreasing inflammation pathologies, and impair the ulcer healing by inhibition of PGE2 production and iNOS expressions and activity in the ulcerated tissue.