Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats
Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats
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DOI：
10.1007/s00383-011-3023-0
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发表时间：
2012-03-01
影响因子：
1.8
通讯作者：
Fukuzawa, Masahiro
中科院分区：
文献类型：
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作者：
Owari, Mitsugu;Wasa, Masafumi;Fukuzawa, Masahiro
高剂量的抗癌药物往往会损害肠粘膜。本研究旨在观察谷氨酰胺对环磷酰胺所致大鼠胃粘膜损伤的影响，并探讨其保护作用的机制。A组（对照组）（n = 8）：腹腔注射生理盐水，B组（n = 8）：腹腔注射环磷酰胺（300 mg/kg），C组（n = 8）：腹腔注射环磷酰胺（300 mg/kg）并口服谷氨酰胺（1.0 g/kg）。3天后，取出回肠段进行形态学和生化分析。TUNEL法检测肠粘膜细胞凋亡，BrdU法检测肠上皮细胞增殖，B组肠粘膜萎缩，A、C组无肠粘膜萎缩。与A组相比，B组黏膜湿重、蛋白质和谷胱甘肽水平显著降低，与B组相比，C组黏膜湿重、蛋白质和谷胱甘肽水平显著升高。与A组相比，B组肠上皮细胞增殖明显减少，凋亡指数明显增加，而C组肠上皮细胞增殖明显增加，凋亡指数明显减少。谷氨酰胺通过增加谷胱甘肽、减少凋亡和增加肠上皮细胞增殖来预防环磷酰胺诱导的肠粘膜损伤。
High doses of anticancer drugs often damage the intestinal mucosa. The purpose of the present study was to examine the effect of glutamine on mucosal damage induced by cyclophosphamide in a rat model, and to elucidate the mechanisms responsible for its protective effects.Rats were randomly assigned to one of the three experimental groups. Group A (control) (n = 8): intraperitoneal injection of saline, group B (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg), group C (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg) and oral glutamine (1.0 g/kg). After 3 days, the ileal segment was removed for morphological and the biochemical analyses. We also evaluated the level of mucosal apoptosis by the TUNEL method and enterocyte proliferation using bromodeoxyuridine (BrdU).Mucosal atrophy was observed in group B but not in groups A or C. The mucosal wet weight, protein and glutathione levels were significantly decreased in group B compared with group A, and were increased significantly in group C compared with group B. While enterocyte proliferation significantly decreased and the apoptotic index significantly increased in group B compared with group A, a significant increase in the enterocyte proliferation and a significant decrease in apoptosis were observed in group C compared with group B.Glutamine prevented intestinal mucosal injury induced by cyclophosphamide via increased glutathione, decreased apoptosis and increased proliferation of intestinal epithelial cells.