塞来昔布对糖尿病胃轻瘫大鼠胃排空的影响

Effects of celecoxib on gastric emptying in diabetic gastroparesis rat

摘要:

目的：探讨塞来昔布（celecoxib）对糖尿病胃轻瘫（diabetic gastroparesis，DGP）大鼠胃排空的影响。方法：雄性SD 大鼠随机分为实验组和正常对照组。采用一次性腹腔注射链脲佐菌素（streptozocin，STZ）并喂食高糖高脂饲料建立糖尿病胃轻瘫模型；正常对照组（normal control，NC，n=7）腹腔注射等量磷酸盐缓冲液并标准饲料喂养。8周后将实验组大鼠随机分为糖尿病胃轻瘫组（DGP组，n=7）、塞来昔布处理组（CE组，n=7）；CE组灌胃塞来昔布 40 mg/（kg·d）共3周。半固体糊残留率法检测大鼠胃排空；荧光定量PCR检测胃窦平滑肌中环氧合酶-2（cyclooxygenase-2，COX-2）mRNA表达；Western blot检测胃窦平滑肌中COX-2蛋白表达；ELISA法检测前列腺素E2（prostaglandin E2，PGE2）表达；电镜观察胃窦平滑肌细胞超微结构。结果：塞来昔布显著改善DGP大鼠胃排空率（F=64.123，P=0.000）；可使大鼠胃窦平滑肌细胞COX-2 mRNA表达（F=9.928，P=0.005）、COX-2蛋白表达（F=28.543，P=0.001）及PGE2表达（F=55.378，P=0.000）下调；DGP大鼠胃窦平滑肌细胞线粒体肿胀、空泡化，CE组仅见少量髓鞘样结构。结论：塞来昔布可能通过COX-2/PGE2通路改DGP大鼠胃排空。

Abstract:

Objective：To investigate the effects of celecoxib on gastric emptying in diabetic gastroparesis rat. Methods：Male SD rats were divided into normal control group，experimental group. Diabetes was induced by intraperitoneal injection of streptozotocin（STZ，50 mg/kg） and diabetic gastroparesis（DGP） was induced by feeding with a high-carbohydrate/high-fat diet. The normal control group（NC group，n=7） was injected with equivalent phosphate buffer solution and fed with standard diet. After 8 weeks，the diabetic rats were randomly divided into two groups ，namely diabetic gastroparesis group（DGP group，n=7） and celecoxib-treated group（CE group，n=7）. The diabetic rats were orally administered with celecoxib [40 mg/（kg·d）] for 3 weeks. Gastric emptying was detected through semisolid method. The mRNA expression of COX-2 was measured by quantitative reverse transcription-PCR. COX-2 protein level was assessed by Western blot. Moreover，prostaglandin E2（PGE2） was quantified by ELISA. The ultrastructural of gastric muscle was evaluated by transmission electron microscopy. Results：Celecoxib significantly improved the gastric emptying of DGP rat（F=64.123，P=0.000）. Meanwhile，celecoxib decreased the expression of COX-2 mRNA（F=9.928，P=0.005） and COX-2 protein（F=28.543，P=0.001） and PGE2（F=55.378，P=0.000） of gastric antral smooth muscle. There were swollen mitochondria and vacuolation in the gastric muscle of DGP rats. Only several myelin figures emerged in celecoxib-treated group. Conclusion：Celecoxib may ame－liorate gastric emptying of DGP rat through inhibition of the COX-2/PGE2 pathway.