Sano Tomoya, Ozaki Kiyokazu, Kodama Yasushi, Matsuura Tetsuro, Narama Isao
Department of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
Exp Toxicol Pathol. 2009 Jul;61(4):371-80. doi: 10.1016/j.etp.2008.10.009. Epub 2008 Dec 9.
A single intravenous injection of alloxan, a non-genotoxic diabetogenic chemical, induces proliferative changes in forestomach mucosa of rats, and some lesions progress to squamous cell carcinoma accompanied with inflammatory change. The present study was conducted to examine the effects of a selective cyclooxygenase-2 (COX-2) inhibitor, etodolac, on the proliferative changes of forestomach mucosa in alloxan-induced diabetic rats. Alloxan-induced diabetic rats were fed a diet containing 0.01% etodolac (AL+Et group) and standard diet (AL group). They were sacrificed after 25 and 50 weeks of feeding, respectively. Squamous cell hyperplasia of forestomach was completely suppressed by etodolac after 25 weeks. After 50 weeks of treatment, the proliferative changes in forestomach developed in all rats of the AL+Et group, but in only 55.6% of the rats in the AL group. The severity of proliferative lesions was much enhanced in the AL+Et group compared to the AL group, and was parallel to the inflammatory changes in individual cases. Ulceration and erosion were more severe in the AL+Et group. These findings demonstrate that etodolac suppresses proliferative and inflammatory changes with COX-2 expression of forestomach in the early stage, but enhances them after 50 weeks.
单次静脉注射四氧嘧啶（一种非基因毒性致糖尿病化学物质）可诱导大鼠前胃黏膜发生增殖性改变，部分病变会进展为鳞状细胞癌并伴有炎症变化。本研究旨在探讨选择性环氧化酶-2（COX-2）抑制剂依托度酸对四氧嘧啶诱导的糖尿病大鼠前胃黏膜增殖性改变的影响。给四氧嘧啶诱导的糖尿病大鼠喂食含0.01%依托度酸的饲料（AL+Et组）和标准饲料（AL组）。分别在喂食25周和50周后将它们处死。25周后，依托度酸完全抑制了前胃的鳞状细胞增生。治疗50周后，AL+Et组所有大鼠的前胃均出现增殖性改变，而AL组只有55.6%的大鼠出现这种改变。与AL组相比，AL+Et组增殖性病变的严重程度明显增强，且在个别病例中与炎症变化平行。AL+Et组的溃疡和糜烂更为严重。这些发现表明，依托度酸在早期可抑制前胃的增殖性和炎症性改变以及COX-2表达，但在50周后会增强这些改变。
