γ-氨基丁酸改善高脂膳食小鼠的骨性能

Effect of γ-Aminobutyric Acid on Bone Performance in High-Fat-Diet-Fed Mice

摘要:

探讨了高脂膳食小鼠补充γ-氨基丁酸(GABA)对骨性能的影响。40只6周龄C57BL/6雄性小鼠,随机分成4组:正常日粮组(control),高脂日粮组(HFD),高脂日粮小鼠饮水补充0.06、0.12 g/dL GABA组。试验结束前一周收集各组小鼠尿液,测定钙及羟脯氨酸含量;第20周结束试验,测定小鼠股骨、胫骨参数,以及股骨氧化还原指标,荧光定量PCR检测相关基因表达。结果显示,与对照组相比,HFD组股骨出现氧化应激,股骨GAD65显著下调、GABAbR显著上调(P＜0.05),GSK3β显著上调而Nrf2显著下调(P＜0.05);股骨和胫骨钙含量、骨强度等相关性能指标显著降低,尿钙及羟脯氨酸含量显著增高,且成骨细胞分化标志基因BGLAP2、col1a1显著下调,破骨细胞分化标志基因RANKL/OPG、CTSK、TRAP显著上调(P＜0.05)。补充0.06、0.12 g/dL GABA可恢复GABAbR、GSK3β、Nrf2表达(P＜0.05),减轻股骨氧化损伤,同时平衡骨细胞分化及代谢,提高股骨和胫骨性能。结果表明,GABA可调节股骨氧化还原状态,平衡骨代谢,改善股骨及胫骨性能;0.12 g/dL GABA改善股骨氧化应激和股骨性能的作用优于0.06 g/dL的。

Abstract:

This manuscript was aimed to investigate the effect of γ-aminobutyric acid on bone performace in high-fat-diet-fed mice. For this,6-week-old C57BL/6 male mice(40) were randomly divided into four groups:normal diet group(C),high-fat diet group(HFD),mice in HFD supplemented with 0.06%,0.12% GABA by drinking water. A week prior to sacrifice,mice were placed in metabolism cages to collect urine for measuring urinary calcium and hydroxyproline content. Mice were sacrificed by 20th,femur,tibia were collected for measuring parameters,femoral oxidative stress and relative genes expression by RT-PCR. The results demonstrated compared with the control group,HFD showed femoral oxidative stress,down-regulated GAD65 and increased GABAbR1 expression as well as dramatically significantly up-regulated GSK3β and down-regulated Nrf2;In addition,mice in HFD showed significantly reduced femoral and tibial performance,while dramatically increased urinary calcium and hydroxyproline content. At the same time,osteoblast-specific genes Col1a1,BGLAP2 significantly down-regulated while osteoclast-specific genes expression RANKL/OPG,TRAP,CTSK increased significantly in HFD. 0.06%,0.12%GABA supplement can significantly recovered GSK3β,Nrf2,GABAbR1 expression,alleviated femoral oxidative stress,and thus improved femur and tibia performance accompanied by balanced bone metabolism. Conclusion:GABA can balance bone metabolism and partially recover bone performance by alleviating oxidative stress. 0.12% GABA showed a better effect than 0.06% in adjusting femoral redox state and improving bone performance.