Vijayalakshhmi Bodiga, Sesikeran Boindala, Udaykumar Putcha, Kalyanasundaram Subramaniam, Raghunath Manchala
Pathology Division, Naitonal Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania PO, Hyderabad 500007, Andhra Pradesh, India.
Free Radic Biol Med. 2005 Jun 15;38(12):1614-24. doi: 10.1016/j.freeradbiomed.2005.02.029. Epub 2005 Mar 30.
Diet influences intestinal growth and function and vitamins modulate intestinal cell turnover. We have assessed the effects of chronic, moderate (50% of control) vitamin restriction and supplementation on intestinal epithelial cell (IEC) apoptosis and the relevance of this to alterations in tissue oxidative stress and antioxidant status. Feeding a vitamin-restricted diet to male, weanling WNIN rats for 20 weeks significantly increased IEC apoptosis, but only in the villi region, as evident from increased annexin V staining, M30 positivity, histological observations, DNA ladder formation, and reduced expression of Bcl-2. This was associated with elevated levels of lipid peroxides and protein carbonyls in the intestinal mucosa despite the increased activities of superoxide dismutase, catalase, and glutathione peroxidase. Consistent with the increased oxidative stress and apoptosis, structural and functional integrity of the villi were compromised as evident from the lowered ratio of villus height:crypt depth and the decreased activities of the membrane marker enzymes alkaline phosphatase and Lys-Ala dipeptidyl aminopeptidase. These changes were reversed by supplementation with a vitamin mixture or vitamin E alone, whereas riboflavin or folic acid supplementation reduced the apoptotic rates, but only partially. Further, oxidative stress was the least in vitamin E- or vitamin mixture-supplemented rats and correlated well with their IEC apoptotic rates. Increased tissue oxidative stress seems to mediate the vitamin-restriction-induced apoptosis of the IECs in rats.
饮食会影响肠道生长和功能，而维生素可调节肠道细胞更新。我们评估了长期适度（对照的50%）维生素限制和补充对肠道上皮细胞（IEC）凋亡的影响，以及这与组织氧化应激和抗氧化状态改变的相关性。给雄性断乳WNIN大鼠喂食维生素限制饮食20周，显著增加了IEC凋亡，但仅在绒毛区域，这从膜联蛋白V染色增加、M30阳性、组织学观察、DNA梯状条带形成以及Bcl-2表达降低中明显可见。尽管超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性增加，但这与肠道黏膜中脂质过氧化物和蛋白质羰基水平升高有关。与氧化应激和凋亡增加一致，绒毛的结构和功能完整性受到损害，这从绒毛高度与隐窝深度比值降低以及膜标记酶碱性磷酸酶和赖氨酰丙氨酸二肽基氨基肽酶活性降低中明显可见。通过补充维生素混合物或单独补充维生素E可逆转这些变化，而补充核黄素或叶酸可降低凋亡率，但只是部分降低。此外，在补充维生素E或维生素混合物的大鼠中氧化应激最小，且与它们的IEC凋亡率密切相关。组织氧化应激增加似乎介导了维生素限制诱导的大鼠IEC凋亡。
