摘要
目的:探讨选择性环氧合酶-2(COX-2)抑制剂塞来昔布(celecoxib)对大鼠实验性Barrett食管发生发展的影响。方法:60只8周龄雄性SD大鼠,50只行食管空肠吻合术2周后随机分为2组。术后4周,塞来昔布组大鼠塞来昔布10 mg/(kg.d-1)经食管灌入;对照组经食管灌入生理盐水1 ml;另外,10只大鼠为假手术组。术后20周处死动物,观察比较3组动物大体组织变化、食管炎、Barrett食管及食管腺癌的发生情况,免疫组织化学检测COX-2的表达,酶联免疫竞争法检测PGE2的水平。结果:术后20周,塞来昔布组轻、中、重度食管炎发生率分别为14/19(73.68%)、4/19(21.05%)、1/19(5.26%);对照组为4/17(23.53%)、5/17(29.41%)、8/17(47.06%),两组比较有显著差异(P<0.05)。Barrett食管发生率塞来昔布组为7/19(36.84%),对照组为13/17(76.47%),两组比较有显著差异(P<0.05)。Barrett食管不典型增生发生率塞来昔布组为2/19(10.53%),对照组为8/17(47.06%),两组比较有显著差异(P<0.05)。COX-2蛋白表达塞来昔布组为1/7(14.29%),对照组为10/13(76.92%),两组比较有显著差异(P<0.05)。塞来昔布组PGE2水平(1480.1±489.8)pg/mg.protein,显著低于对照组(2933.8±862.9)pg/mg.protein(P<0.001)。假手术组组织学未见异常。结论:塞来昔布对大鼠反流性食管炎、Barrett食管和食管腺癌的发生发展有化学预防作用。
Objective: To examine the chemopreventive effect of selective cyclooxygenase-2 (COX-2) inhibitor celeeoxib for Barrettes esophagus in rats. Methods: Fifty 8-week-old male Sprague Dawley rats underwent esophagojejunostomy to induce Barrett's esophagus model. Four weeks after operation the animals were given celecoxib 10 mg/(kg·d^-1) (celecoxib group),or saline 1 ml (control group). Another 10 rats were sham operation group. All animals were sacrificed at 20 week after surgery. The degree of inflammation, Barrett' s esophagus, adenocarcinoma,COX-2 expression and PGE2 of animals were assessed. Results: Among 60 rats, 6 rats died in celecoxib group, 8 rats died in control group, 1 rat died in sham operation group ,and 45(75%) rats completed the study. The incidence of mild,moderate and severe degree esophageal inflammation in celecoxib group and control group was 14/19(73.68%),4/19(21.05%),1/19 (5.26%) ;4/17(23.53%) ,5/17 (29.41%), 8/17(47.06%) (P〈0.05) ,respectively. The incidence of Barrett's esophagus was 7/19 (36.84%),13/17(76.47%) in two group respectively (P 〈 0.05) ;The incidence of Barrett's esophagus with dysplasia was 2/19(10.53%),8/17(47.06%) (P 〈 0.05), respectively. The expression of COX-2 was 1/7 (14.29%), 10/13 (76.92 %) (P 〈0.05) in two groups. PGE2 content was significantly lower in the celecoxib group than that in control group (P〈 0. 001). No esophageal pathological changes were found in sham operation group. Conclusion: Selective COX-2 inhibitors celecoxib can inhibit inflammations,development of Barrett's esophagus and esophagus adenocarcinoma.
出处
《浙江大学学报(医学版)》
CAS
CSCD
北大核心
2009年第5期498-504,共7页
Journal of Zhejiang University(Medical Sciences)