Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bnai Zion Medical Center, Haifa, Israel.
Br J Nutr. 2013 Jan 14;109(1):89-98. doi: 10.1017/S0007114512000542. Epub 2012 Mar 28.
Growing evidence suggests that n-3 PUFA and their specific lipid mediators can reduce the activity of inflammatory processes. In the present study, we evaluated the effects of oral n-3 PUFA supplementation on intestinal structural changes, enterocyte proliferation and apoptosis during methotrexate (MTX)-induced intestinal damage in the rat. A total of thirty-two male rats were divided into four experimental groups: control (CONTR) rats; CONTR-n-3 PUFA rats treated with oral administration of n-3 PUFA at a dose of 300 μg/kg once per d 72 h before and 72 h following vehicle injection; MTX rats treated with a single dose of MTX; MTX-n-3 PUFA rats treated with oral n-3 PUFA following the injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis determined 72 h following MTX injection. Real-time PCR was used to determine B-cell lymphoma 2 (Bcl2)-associated X protein (Bax) and Bcl2 mRNA expression. Western blotting was used to determine phosphorylated extracellular signal-related kinase, β-catenin, Bax and Bcl2 protein levels. MTX-n-3 PUFA rats demonstrated a greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in the jejunum and ileum and crypt depth in the ileum, compared with MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-n-3 PUFA rats (v. MTX) was accompanied by decreased Bax mRNA and protein expression and increased Bcl2 mRNA levels. Thus, the treatment with oral n-3 PUFA prevented mucosal injury and improved intestinal recovery following MTX-injury in rats.
越来越多的证据表明，n-3PUFA 及其特定的脂质介质可以降低炎症过程的活性。在本研究中，我们评估了口服 n-3PUFA 补充剂对大鼠甲氨蝶呤（MTX）诱导的肠损伤过程中肠结构变化、肠上皮细胞增殖和凋亡的影响。总共 32 只雄性大鼠分为四组：对照组（CONTR）大鼠；CONTR-n-3PUFA 大鼠，在 MTX 注射前 72 小时和后 72 小时，每日口服给予 n-3PUFA300μg/kg；MTX 大鼠，单次 MTX 注射；MTX-n-3PUFA 大鼠，在 MTX 注射后口服 n-3PUFA。MTX 注射后 72 小时，确定肠黏膜损伤、黏膜结构变化、肠上皮细胞增殖和肠上皮细胞凋亡。实时 PCR 用于确定 B 细胞淋巴瘤 2（Bcl2）相关 X 蛋白（Bax）和 Bcl2mRNA 表达。Western blot 用于确定磷酸化细胞外信号相关激酶、β-连环蛋白、Bax 和 Bcl2 蛋白水平。与 MTX 动物相比，MTX-n-3PUFA 大鼠的空肠和回肠肠重、回肠黏膜重、回肠黏膜 DNA 和蛋白水平、空肠和回肠绒毛高度以及回肠隐窝深度均增加。MTX-n-3PUFA 大鼠回肠上皮细胞凋亡明显减少（与 MTX 相比），同时 BaxmRNA 和蛋白表达减少，Bcl2mRNA 水平升高。因此，口服 n-3PUFA 治疗可预防 MTX 损伤后大鼠的黏膜损伤并改善肠恢复。
