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目的探讨γ-氨基丁酸(GABA)对高脂膳食小鼠免疫功能的影响及其机制。方法 30只雄性C57BL/6小鼠被随机分为正常组(正常饲料),高脂组(高脂饲料),GABA干预组(高脂饲料,饮用水中加入2 mg/ml的GABA)饲喂20周后,测定小鼠体质量和胸腺、脾脏脏器指数,流式检测小鼠外周血中CD4+细胞、CD8+细胞和CD4+CD25+CD127-/low调节性T细胞(regulatory T cell,Treg)的比例,分选出外周血Treg并测其活性氧(reactive oxygen species,ROS)、线粒体膜电位水平及基因Nrf2、GSK-3βmRNA表达水平。结果高脂膳食小鼠胸腺、脾脏脏器指数、CD4+/CD8+比值、Treg比例的显著下降显示其免疫功能受到损伤。Treg中的ROS水平显著上升,线粒体膜电位下降。Nrf2 mRNA表达水平显著下调,GSK-3βmRNA表达水平显著上调,并且基因的表达水平与Treg的ROS水平和线粒体膜电位水平显著相关。通过添加GABA能够有效改善高脂膳食诱导的机体免疫功能损伤,并可能通过GSK-3β、Nrf2基因的作用来减少过量ROS导致的调节性T细胞线粒体膜电位降低。结论长期高脂膳食可导致免疫功能损伤,GABA能够改善免疫功能并通过清除自由基来减少调节性T细胞凋亡。
Objective To investigate the effect and mechanism of γ-aminobutyric acid (GABA) on immune function in high-fat diet mice. Methods Thirty male C57BL / 6 mice were randomly divided into normal group (fed with normal diet), high fat diet (fed with high fat diet), GABA intervention group (fed with high fat diet and 2 mg / ml GABA in drinking water) After 20 weeks, the body weight, thymus and spleen organ index of mice were determined, and the CD4 + cells, CD8 + cells and CD4 + CD25 + CD127- / low regulatory T cells (Tregs) (Treg). The levels of reactive oxygen species (ROS), mitochondrial membrane potential and Nrf2, GSK-3βmRNA were detected. Results The significant decrease of thymus and spleen organ index, CD4 + / CD8 + ratio and Treg ratio in high fat diet mice showed that the immune function was impaired. The levels of ROS in Tregs increased significantly and mitochondrial membrane potential decreased. Nrf2 mRNA expression was significantly down-regulated, GSK-3β mRNA expression was significantly up-regulated, and the gene expression level was significantly correlated with Treg ROS level and mitochondrial membrane potential. By adding GABA can effectively improve the high-fat diet-induced immune dysfunction and may reduce the excessive ROS-mediated regulatory T cell mitochondrial membrane potential by GSK-3β, Nrf2 gene role. CONCLUSIONS Long-term high-fat diet can cause damage to immune function. GABA can improve immune function and reduce apoptosis of regulatory T cells by eliminating free radicals.