Hashimoto Naoki
Naoki Hashimoto, Department of Surgery, Kinki University, Osaka 589-8511, Japan.
World J Gastroenterol. 2014 Jun 7;20(21):6541-6. doi: 10.3748/wjg.v20.i21.6541.
To examine the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in rat esophageal lesions induced by reflux of duodenal contents.
Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy to elicit chronic esophagitis. In ten rats sham operations with only a midline laparotomy were performed (Control). The rats were sacrificed at the 40(th) week, their esophagi were taken for hematoxylin and eosin staining and for examination of expression of COX2, PGE2, and proliferating cell nuclear antigen (PCNA), and total bile acids in the esophageal lumen was measured.
After 40 wk of reflux, columnar dysplasia, squamous cell carcinoma and adenocarcinoma were observed. Total bile acids in the esophageal lumen were significantly increased in the EDA group compared with the sham operated rats. PCNA labelling index and esophageal tissue PGE2 levels were higher in dysplastic and cancer tissues than in control tissues. Overexpression of COX2 was observed in dysplastic and cancer tissues.
Reflux of duodenal contents induces COX2 expression and increases prostaglandin synthesis in dysplastic and cancer tissues. This result suggests a possible mechanism by which bile acids promote esophageal cancer.
检测十二指肠内容物反流诱导的大鼠食管病变中环氧化酶-2(COX-2)和前列腺素E2(PGE2)的表达。
将30只8周龄雄性Wistar大鼠暴露于十二指肠内容物食管反流。所有动物均接受食管十二指肠吻合术(EDA)并全胃切除术以引发慢性食管炎。对10只大鼠仅进行中线剖腹术作为假手术(对照组)。在第40周处死大鼠,取其食管进行苏木精-伊红染色,检测COX2、PGE2和增殖细胞核抗原(PCNA)的表达,并测量食管腔内总胆汁酸。
反流40周后,观察到柱状上皮发育异常、鳞状细胞癌和腺癌。与假手术大鼠相比,EDA组食管腔内总胆汁酸显著增加。发育异常和癌组织中的PCNA标记指数及食管组织PGE2水平高于对照组织。在发育异常和癌组织中观察到COX2过表达。
十二指肠内容物反流诱导COX2表达,并增加发育异常和癌组织中前列腺素的合成。该结果提示了胆汁酸促进食管癌发生的一种可能机制。