Laboratory Animal Research Center, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
J Toxicol Sci. 2012;37(6):1261-5. doi: 10.2131/jts.37.1261.
Metallothionein (MT), a low-molecular-weight protein with a high affinity for divalent heavy metal ions, is involved in many pathophysiological processes, including metal homeostasis, detoxification, cell proliferation and protection against oxidative damage. We previously found that MT in gastric mucosa plays a role in protecting against Helicobacter pylori (H. pylori)-induced gastritis at the early stage of infection. H. pylori-induced chronic gastric inflammation is shown to be associated with gastric carcinogenesis. Thus, to examine whether gastric MT contributes to protection against H. pylori-induced chronic inflammation, we compared histological changes in the gastric mucosa of MT-null and the wild-type mice at 53 weeks after inoculation three times with H. pylori SS1. As a result, we observed disruption of the gastric mucosa in MT-null mice, but not in the wild-type mice, even at the late stage of H. pylori-infection. Evaluation of pathological changes in gastric specimens by the updated Sydney grading system revealed that scores related to chronic inflammation and polymorphonuclear cell activity were higher in infected MT-null mice than those in the wild-type mice. Furthermore, a higher score for metaplasia was also observed in the MT-null stomach. These results suggested that MT might be involved in protecting against H. pylori-induced gastric chronic inflammation associated with carcinogenesis.
金属硫蛋白（MT）是一种与二价重金属离子具有高亲和力的低分子量蛋白质，参与许多病理生理过程，包括金属内稳态、解毒、细胞增殖和防止氧化损伤。我们之前发现胃黏膜中的 MT 在感染早期对幽门螺杆菌（H. pylori）引起的胃炎起保护作用。H. pylori 引起的慢性胃炎症与胃癌的发生有关。因此，为了研究胃 MT 是否有助于防止 H. pylori 引起的慢性炎症，我们比较了在 H. pylori SS1 接种三次后 53 周时 MT 缺失和野生型小鼠胃黏膜的组织学变化。结果，我们观察到 MT 缺失小鼠的胃黏膜紊乱，但野生型小鼠没有，即使在 H. pylori 感染的晚期也是如此。使用更新的悉尼分级系统对胃标本的病理变化进行评估显示，感染 MT 缺失小鼠的慢性炎症和多形核细胞活性相关评分高于野生型小鼠。此外，MT 缺失胃中还观察到更高的化生评分。这些结果表明 MT 可能参与防止与致癌有关的 H. pylori 诱导的胃慢性炎症。
