萘丁美酮在混合反流模型干预治疗中的作用

The preventive effect of nabumetone in the model of reflux esophagitis

目的探讨萘丁美酮在混合反流模型干预治疗中的作用。方法健康SD大鼠100只,随机分为反流模型组(Y组,46只)、萘丁美酮组(R组,46只)和正常对照组(C组,8只)。分别观察Y组、R组术后5、17、28、40周及C组40周时食管黏膜的病理改变,检测环氧合酶-2(COX-2)、增殖细胞核抗原(PCNA)、细胞周期蛋白D1(CD1)的表达情况。结果①R组不同时段的损伤积分和Barrett食管(BE)的发生率均低于Y组。②Y组COX-2、PCNA及CD1从正常→反流性食管炎(RE)→BE→食管腺癌(EAC)的阳性表达率和表达程度逐渐增强。③R组不同时段COX-2、PCNA、CD1的表达均低于Y组,且COX-2表达程度和阳性表达率与Y组相比均有统计学意义(P<0.05);R组40周PCNA的表达程度及阳性表达率与Y组相比有统计学差异(P<0.05)。结论COX-2、PCNA和CD1基因的高表达参与了从RE→BE→EAC的发展过程,是BE、EAC发生、发展的早期分子事件。萘丁美酮可影响COX-2、PCNA和CD1的表达,减轻炎症的程度并减缓病程的进展,降低BE和重度不典型增生的发生率,抑制腺癌的发生。

Objective To investigate the preventive effect of nabumetone on the damaged esophageal mucosa in the model of reflux esophagitis, and the effect of expression of cyclooxygenase-2 （COX-2）, proliferating cell nuclear antigen（PCNA）, cyclin D1 （CD1） on the progress of reflux esophagitis. Methods A total of 100 SD rats were divided into three groups in random： group Y： operation ＋ saline as positive controls（46） ; group R： operation ＋ nabumetone（46） ; and group C： normal control（8）. The lesions of esophageal mucosa were observed in the 5th, 17th, 28th , 40th week in groups Y and R and 40th week in group C, respectively. The change of COX-2, PCNA, and CD1 by immunoperoxidase staining in the progress of reflux esophagitis（RE） and the effect of nabumetone were evaluated. Results ① The lesions of esophageal mucosa at different time and the incidence of Barrett＇s esophagus （BE） in group R were lower than those in group Y （P〈0.05）.② The expressions of COX-2, PCNA and CD1 increased gradually from normal→RE→BE→esophageal adenocacinoma （EAC） in group Y. ③ The expressions of COX-2, PCNA and CD1 in group R were lower than those in group Y at different time, and the expression of COX- 2 significantly differed between group Y and R（P〈0.05）. Conclusion In the progress of RE, COX-2, PCNA, and CD1 increase gradually. Nabumetone reduces mucosa injury in RE and inhibits the development of BE by affecting the expression of COX-2, PCNA, and CD1.