4-苯基丁酸对高果糖喂养大鼠肝脏脂质沉积及氧化应激的影响

Effect of 4-phenyl Butyric Acid on Hepatic Lipid Deposition and Oxidative Stress Induced by High-fructose Feeding in Mice

目的观察内质网应激(ERS)抑制剂4-苯基丁酸(4-PBA)对高果糖饮食喂养大鼠肝脏氧化应激的影响,以探讨ERS在高果糖喂养诱导脂肪肝中的介导作用及其与氧化应激的关系。方法雄性Wistar大鼠分为对照组、高果糖组和4-PBA组[自高果糖喂养4周后给予4-PBA 0.35 g/(kg·d)],8周后处死大鼠并测定肝脏甘油三酯(TG)含量。PCR法检测ERS标志物葡萄糖调节蛋白78(GRP78)的基因表达。测定细胞中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性及细胞中丙二醛(MDA)的含量。Western blot法检测肝C/EBP同源蛋白(CHOP)。结果与对照组相比,高果糖组的肝脏TG含量、GRP78基因表达、CHOP蛋白表达显著增加(P<0.01),与高果糖组比较,4-PBA上述指标显著降低(P<0.01)。与对照组相比,高果糖组大鼠的SOD、GSH-Px、CAT活性下降,MDA含量升高(P均<0.01),而4-PBA组的SOD、GSH-Px、CAT活性高于高果糖组,MDA含量低于高果糖组(P均<0.01)。结论长期高果糖喂养可诱导肝脏ERS和氧化应激,ERS抑制剂4-PBA可改善高果糖饮食诱导的肝脏氧化应激。

Objective To observe the effect of 4-phenyl butyric acid [4-PBA,an endoplasmic reticulum stress（ ERS） inhibitor]on hepatic oxidative stress induced by high-fructose feeding in mice and to investigate the effect of ERS mediation and its relationship with oxidative stress. Methods A total of 46 male Wistar rats were divided into control group（ n = 15）,high-fructose feeding group（ n = 15） and 4-PBA intervention group（ n = 16） [0. 35 g /（ kgod） 4-PBA intervention was initiated in 4thweek of high-fructose feeding]. After 8 weeks of feeding,all rats were sacrificed,and hepatic triglyceride（ TG） contents were detected. The expression of glucose regulated protein 78（ GRP78） was detected with polymerase chain reaction（ PCR） method. Activities of superoxide dismutase（ SOD）,catalase（ CAT） and glutathione peroxidase（ GSH-Px） and malondialdehyde（ MDA） contents were detected. The expression of C / EBP homologous protein（ CHOP） was detected with Western blot method. Results In high-fructose feeding group,the values of TG content and GRP78 and CHOP expressions were significantly increased compared with those in control group（ P〈0. 01）;while the above values were significantly decreased in 4-PBA intervention group compared with those in high-fructose feeding group（ P〈0. 01）. In high-fructose feeding group,the values of SOD,GSH-Px and CAT activities were significantly decreased,while MDA content was increased more than those in the control group（ P〈0. 01）; in 4-PBA intervention group,the values of SOD,GSH-Px and CAT activities were significantly higher,while MDA content was lower than those in high-fructose feeding group（ P〈0. 01）. Conclusion Long-term high-fructose feeding can induce hepatic ERS and oxidative stress,and 4-phenyl butyric acid can improve hepatic oxidative stress induced by high-fructose feeding.