Verburg M, Renes I B, Meijer H P, Taminiau J A, Büller H A, Einerhand A W, Dekker J
Laboratory of Pediatric Gastroenterology and Nutrition, Erasmus University and Sophia Children's Hospital, 3015GE Rotterdam, The Netherlands.
Am J Physiol Gastrointest Liver Physiol. 2000 Nov;279(5):G1037-47. doi: 10.1152/ajpgi.2000.279.5.G1037.
Proliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths of small intestinal crypts in a proximal-to-distal decreasing gradient along the small intestine. The remaining crypt epithelium appeared flattened, except for Paneth cells, in which lysozyme protein and mRNA expression was increased. Regeneration through increased proliferation during days 3-4 coincided with villus atrophy, showing decreased numbers of villus enterocytes and decreased expression of the enterocyte-specific genes sucrase-isomaltase and carbamoyl phosphate synthase I. Remarkably, goblet cells were spared at villus tips and remained functional, displaying Muc2 and trefoil factor 3 expression. On days 8-10, all parameters had returned to normal in the whole small intestine. No methotrexate-induced changes were seen in epithelial morphology, proliferation, apoptosis, Muc2, and TFF3 immunostaining in the colon. The observed small intestinal sparing of Paneth cells and goblet cells following exposure to methotrexate is likely to contribute to epithelial defense during increased vulnerability of the intestinal epithelium.
在用甲氨蝶呤治疗后，对大鼠小肠和结肠上皮的增殖、分化及细胞死亡情况进行了研究。治疗后第1至2天的特征为增殖减少、凋亡增加，且小肠隐窝数量和深度沿小肠近端至远端呈递减梯度下降。除潘氏细胞外，其余隐窝上皮细胞显得扁平，而潘氏细胞中溶菌酶蛋白和mRNA表达增加。在第3至4天，通过增殖增加实现的再生与绒毛萎缩同时出现，表现为绒毛肠上皮细胞数量减少以及肠上皮细胞特异性基因蔗糖酶 - 异麦芽糖酶和氨甲酰磷酸合成酶I的表达降低。值得注意的是，杯状细胞在绒毛顶端得以保留并保持功能，表现出Muc2和三叶因子3的表达。在第8至10天，整个小肠的所有参数均恢复正常。在结肠中，未观察到甲氨蝶呤诱导的上皮形态、增殖、凋亡、Muc2和TFF3免疫染色的变化。甲氨蝶呤暴露后观察到的小肠中潘氏细胞和杯状细胞的保留，可能有助于在肠上皮易损性增加期间的上皮防御。
