谷氨酰胺对甲氨蝶呤所致大鼠肠黏膜炎症的保护作用  

The protective effect of glutamine on methotrexate- induced rat intestinal inflammation

作　　者：何秋颖[1] 孙梅[1] 

机构地区：[1]中国医科大学附属盛京医院儿科,辽宁沈阳110020

出　　处：《现代肿瘤医学》2015年第4期457-460,共4页Journal of Modern Oncology

摘　　要：目的:通过研究甲氨蝶呤(methotrexate,MTX)模型鼠小肠炎症,观察谷氨酰胺(glutamine,GLN)对MTX所致大鼠肠黏膜的保护作用及肠黏膜炎时紧密连接蛋白的变化,探讨GLN保护作用的可能机制。方法:SD大鼠随机分为三组,每组8只。CON组(control group):腹腔注射生理盐水(normal saline,NS)1ml连续2天,每日口服灌胃NS 1ml。MTX组:腹腔注射MTX 1ml(20mg/kg)连续2天,每日口服灌胃NS 1ml。GLN组:腹腔注射MTX 1ml(20mg/kg)连续2天,每日口服灌胃GLN 1ml[2g/(kg·d)]。各组大鼠于注射MTX后第8天处死,观察MTX模型鼠小肠炎症时一般状态、免疫组化、荧光实时定量PCR检测紧密连接蛋白的表达。结果:GLN组、MTX组与对照组比较Occludin和Claudin-1的基因表达水平均有减低,较对照组有显著差异(P<0.05)。MTX组的基因表达均较GLN组有所下调,差异显著(P<0.05),GLN组表达相对增加,提示肠黏膜炎时对紧密连接蛋白表达有保护作用。结论:MTX可诱导鼠发生小肠炎症,GLN对肠黏膜炎症有保护作用,其作用机制可能与肠上皮细胞间紧密连接蛋白调节有关。Objective：Chemotherapy often leads to gastrointestinal mucosa injury and increased intestinal permea- bility. In the article we studied the intestinal inflammation of MTX - treated rats, which further revealed tight junction protein of intestinal mucositis changed, and whether glutamine had protected affection. Methods ： SD rats were randomly divided into three groups each group with eight. Control group （CON group） ：Daily intraperitoneal injection of saline 1 ml for 2 days and intragastric administration of saline 1 ml every day. MTX group：Intraperitoneal injection of MTX 1 ml （20mg/kg） for 2 consecutive days and intragastric administration of saline 1 ml every day. GLN group：Intra- peritoneal injection of MTX lml（20mg/kg） for 2 consecutive days while daily oral gavage administration of GLN lml [ 2g/（ kg · d） ]. All rats were executed on 8 days after injection of MTX, observing the general status of intestinal in- flammation, using immunohistochemistry, Real time quantitative Polymerase chain reaction to detect the expression of tight junction proteins. Results： Occludin, Claudin- 1 protein expression was decreased in the MTX group and GLN group compared with the control group （ P 〈 0.05 ）, the GLN group and the MTX group were different in protein ex- pression（P 〈 0.05 ）. GLN group relative increased, suggesting that it had protective effect on tight junction proteins when the intestinal inflammation. Conclusion：MTX can induce murine intestinal inflammation, glutamine has a pro- tective effect on intestinal inflammation,and its mechanism may be related to the regulation of the tight junction pro- tein in intestinal epithelial cells.

关 键 词：甲氨蝶呤 谷氨酰胺 肠黏膜炎 OCCLUDIN CLAUDIN-1 

分 类 号：R730.53[医药卫生—肿瘤]