环氧合酶-2在反流性食管炎大鼠食管组织中表达的实验研究

Cyclooxygenase-2 Expression in Esophageal Tissues of Rats with Experimental Reflux Esophagitis

背景:环氧合酶(COX)-2在炎症、肿瘤等的发生、发展过程中发挥重要作用,但其在反流性食管炎(RE)中的作用尚未明确。目的:研究COX-2在混合性RE大鼠食管组织中的表达,探讨COX-2的表达与RE的关系。方法:采用贲门肌切开术加十二指肠半结扎术建立混合性RE大鼠模型。22只健康Sprague-Dawley大鼠随机分为RE模型组(n=12)和假手术组(n=10),于术前和术后1周测定食管下段和胃液pH值。处死大鼠,分别应用放射免疫测定和免疫组化方法检测食管组织中前列腺素(PG)E2的含量和COX-2的表达,光镜观察食管组织的形态学改变。结果:RE模型组术后食管下段pH值显著低于假手术组(P<0.05),胃液pH值则显著高于假手术组(P<0.05);食管组织PGE2含量亦较假手术组显著增高(P<0.001),COX-2表达均为阳性,假手术组食管组织中无COX-2表达。光镜观察显示RE模型组食管黏膜病理损害明显。结论:COX-2高表达和PGE2含量增高参与了混合性RE的发生、发展过程,COX-2可能通过升高PGE2含量而在RE的发病中起重要作用。

Background： Cyclooxygenase （COX）-2 plays an important role in the progression of inflammation and development of tumors, but its role in reflux esophagitis （RE） has not been clarified yet. Aims： To observe the COX-2 expression in esophageal tissues of rat model with mixed RE and to appraise the relationship between COX-2 expression and RE. Methods： The mixed RE model was constructed by cardiomyotomy （1 cm longitudinally across the gastroesophageal junction） and partial ligation of duodenum in healthy Sprague-Dawley rats. Twenty-two rats were randomly divided into two groups： RE model group （n=12） and sham operation group （n=10）. The lower esophageal and gastric juice pH values were measured before and one week after operation. Then the animals were sacrificed, the prostaglandin （PG） E2 content in the esophageal tissues was detected by radioimmunoassay, and the expression of COX-2 studied immunohistochemically. The morphological changes of esophageal tissues were observed by light microscopy. Results： The postoperative lower esophageal pH value was significantly lower, and both the gastric juice pH value and the PGE2 content in the esophageal tissues were significantly higher in RE model group than those in the sham operation group （P〈0.05, P〈0.05, and P〈0.001, respectively）. Positive expression of COX-2 in esophageal tissues was observed in RE model group, but not in sham operation group. The inflammation of esophageal mucosa in RE model group was more severe. Conclusions： The expression of COX-2 and the content of PGE2 are up-regulated markedly in rat model with mixed RE, and these are likely to contribute to the development of RE. It is suggested that COX-2 might play an important role in the pathogenesis of RE with increased PGE2 content.