Yoshizawa Nao, Takenaka Yoshiharu, Yamaguchi Hirokazu, Tetsuya Tsukamoto, Tanaka Harunari, Tatematsu Masae, Nomura Sachiyo, Goldenring James R, Kaminishi Michio
Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Lab Invest. 2007 Dec;87(12):1265-76. doi: 10.1038/labinvest.3700682.
Spasmolytic polypeptide (TFF2)-expressing metaplasia (SPEM) is observed in mucosa adjacent to human gastric cancer and in fundic glands showing oxyntic atrophy in Helicobacter felis-infected mice. Mongolian gerbils infected with Helicobacter pylori (Hp) develop goblet cell intestinal metaplasia and adenocarcinoma, but the presence of SPEM has not been studied in gerbils. We therefore have sought to examine the development of metaplastic mucosal changes in Hp-infected Mongolian gerbils. Mongolian gerbils were assigned to either uninfected controls or infected with Hp at 17 weeks of age. The animals were killed at 17, 20, 26, 31, 41 and 56 weeks of age. Stomach sections were stained using antibodies for TFF2, intrinsic factor, H/K-ATPase, BrdU and MUC2. Dual immunofluorescence staining for TFF2 with intrinsic factor and for TFF2 with MUC2 was performed. In uninfected animals, no SPEM or intestinal metaplasia was observed. Infected gerbils developed SPEM initially in the intermediate zone along the lesser curvature and subsequently spread out towards the greater curvature. In the earlier stages of infection, SPEM glands demonstrated TFF2 and intrinsic factor double staining cells. However, after 35 weeks of infection, the number of double staining SPEM cells decreased. While early in infection SPEM organized in straight glands, in the later stages of infections, SPEM glands became distorted or dilated along with the development of gastritis cystica profunda that was TFF2 positive. Goblet cell intestinal metaplasia developed only late in the infection. Dual staining for TFF2 and MUC2 showed glands containing both SPEM- and MUC2-positive goblet cell intestinal metaplasia. SPEM develops early in Hp infection in Mongolian gerbils, and alterations in gland morphology arise from SPEM glands during the course of gastric infection with goblet cell intestinal metaplasia developing subsequent to SPEM.
在人类胃癌邻近的黏膜以及感染猫螺旋杆菌的小鼠中出现胃体萎缩的胃底腺中，可观察到表达解痉多肽（TFF2）的化生（SPEM）。感染幽门螺杆菌（Hp）的蒙古沙鼠会发生杯状细胞肠化生和腺癌，但尚未在沙鼠中研究过SPEM的存在情况。因此，我们试图研究感染Hp的蒙古沙鼠化生黏膜变化的发展情况。将蒙古沙鼠分为未感染对照组或在17周龄时感染Hp组。在17、20、26、31、41和56周龄时处死动物。胃切片用针对TFF2、内因子、H/K-ATP酶、BrdU和MUC2的抗体进行染色。对TFF2与内因子以及TFF2与MUC2进行双重免疫荧光染色。在未感染的动物中，未观察到SPEM或肠化生。感染的沙鼠最初在沿小弯的中间区域出现SPEM，随后向大弯扩散。在感染的早期阶段，SPEM腺显示TFF2和内因子双重染色细胞。然而，在感染35周后，双重染色的SPEM细胞数量减少。虽然在感染早期SPEM形成直的腺，但在感染后期，随着深部囊性胃炎（TFF2阳性）的发展，SPEM腺变得扭曲或扩张。杯状细胞肠化生仅在感染后期出现。TFF2和MUC2的双重染色显示腺体同时含有SPEM阳性和MUC2阳性的杯状细胞肠化生。SPEM在蒙古沙鼠Hp感染早期出现，在胃感染过程中，腺形态的改变源于SPEM腺，杯状细胞肠化生在SPEM之后出现。
