Lee Chung-Wei, Wang Xiang-Dong, Chien Kuo-Liong, Ge Zhongming, Rickman Barry H, Rogers Arlin B, Varro Andrea, Whary Mark T, Wang Timothy C, Fox James G
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Int J Cancer. 2008 Mar 1;122(5):1068-76. doi: 10.1002/ijc.23228.
In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C-deficient B6.129P2-Gulo(tm1Umc/mmcd) (gulo(-/-)) mice lacking L-gulono-gamma-lactone oxidase, we compared gastric lesions and Th1 immune responses in H. pylori-infected gulo(-/-) mice supplemented with low (33 mg/L) or high (3,300 mg/L) vitamin C in drinking water for 16 or 32 weeks. Vitamin C levels in plasma and gastric tissue correlated with the vitamin C supplementation levels in gulo(-/-) mice. H. pylori infection resulted in comparable gastritis and premalignant lesions in wildtype C57BL/6 and gulo(-/-) mice supplemented with high vitamin C, but lesions were less severe in gulo(-/-) mice supplemented with low vitamin C at 32 weeks post infection. The reduced gastric lesions in infected gulo(-/-) mice supplemented with low vitamin C correlated with reduced Th1-associated IgG2c, gastric IFN-gamma and TNF-alpha mRNA and higher H. pylori colonization levels. These results in the H. pylori-infected gulo(-/-) mouse model suggest that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect gulo(-/-) mice from H. pylori-induced premalignant gastric lesions. In addition, less severe gastric lesions in H.pylori infected gulo(-/-) mice supplemented with low vitamin C correlated with an attenuated Th1 inflammatory response.
在人体研究中，维生素C摄入量低与更严重的幽门螺杆菌胃炎以及更高的胃癌发病率相关。然而，补充维生素C尚未被明确证明可预防胃癌。我们使用缺乏L-古洛糖酸-γ-内酯氧化酶的维生素C缺乏型B6.129P2-Gulo(tm1Umc/mmcd)（gulo(-/-)）小鼠，比较了饮用水中补充低剂量（33毫克/升）或高剂量（3300毫克/升）维生素C 16周或32周的幽门螺杆菌感染gulo(-/-)小鼠的胃部病变和Th1免疫反应。血浆和胃组织中的维生素C水平与gulo(-/-)小鼠的维生素C补充水平相关。幽门螺杆菌感染在补充高剂量维生素C的野生型C57BL/6和gulo(-/-)小鼠中导致了相当的胃炎和癌前病变，但在感染后32周补充低剂量维生素C的gulo(-/-)小鼠中病变较轻。补充低剂量维生素C的感染gulo(-/-)小鼠胃部病变减少与Th1相关的IgG2c、胃IFN-γ和TNF-α mRNA减少以及更高的幽门螺杆菌定植水平相关。在幽门螺杆菌感染的gulo(-/-)小鼠模型中的这些结果表明，尽管补充高剂量维生素C在血浆和胃组织中达到了生理正常的维生素C水平，但该剂量的维生素C并未保护gulo(-/-)小鼠免受幽门螺杆菌诱导的癌前胃部病变。此外，补充低剂量维生素C的幽门螺杆菌感染gulo(-/-)小鼠中较轻的胃部病变与减弱的Th1炎症反应相关。
