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[目的]探讨5-氨基乙酰丙酸(5-ALA)对内质网应激水平及肥胖小鼠糖代谢的影响及相关分子机制。[方法]将10只8周龄C57BL/6J小鼠适应性喂养1周后,高脂饲料喂养16周诱导造模肥胖小鼠,将肥胖小鼠随机分为5-ALA处理组[5-ALA灌胃5 mg/(kg·d)]和对照组[磷酸盐缓冲液(PBS)灌胃1mL/(kg·d)],连续9周,期间每周于空腹12 h后尾静脉取血检测小鼠的空腹血糖。9周后分离小鼠的肝脏和附睾脂肪组织提取RNA和蛋白,检测小鼠肝脏和脂肪组织中内质网应激相关基因C/EBP同源蛋白(CHOP)、X-盒结合蛋白1s(XBP-1s)、重链结合蛋白(Bi P)、内质网Dnaj同系物4(ERdj4)的表达水平。[结果]5-ALA处理小鼠空腹血糖于第5周[(6.40±0.35)mmol/L]开始下降,波动变小,第7周5-ALA处理组空腹血糖水平[(6.02±0.17)mmol/L]低于对照组[(6.54±0.05)mmol/L](P<0.05)。实时聚合酶链反应(real-time PCR)结果显示,5-ALA可抑制由于肥胖导致的脂肪组织中XBP-1s的高表达(5-ALA处理组2-△△CT为0.029±0.017,对照组为0.029±0.006),P<0.05;western blotting结果亦显示5-ALA处理组小鼠XBP-1s水平低于对照组。[结论]5-ALA可能通过抑制白色脂肪组织中内质网应激通路IRE1-XBP-1通路缓解内质网应激水平,改善小鼠的血糖代谢。
[Objective] To investigate the effect of 5-aminolevulinic acid (5-ALA) on the endoplasmic reticulum stress level and the glucose metabolism in obese mice and related molecular mechanisms. [Method] Ten 8-week-old C57BL / 6J mice were fed adaptively for 1 week, and the obese mice were induced by high-fat diet for 16 weeks. The obese mice were randomly divided into 5-ALA group [5-ALA (5 mg / (kg · d)) and control group (1 mL / (kg · d) for phosphate buffered saline) for 9 weeks. The tail vein blood was taken 12 h after fasting Fasting blood glucose in mice. After 9 weeks, the liver and epididymal adipose tissue were isolated from the mice to extract RNA and protein. The endoplasmic reticulum stress related genes C / EBP homologous protein (CHOP), X-box binding protein 1s (XBP -1s), heavy chain binding protein (Bi P), endoplasmic reticulum Dnaj homolog 4 (ERdj4). [Results] The fasting blood glucose of 5-ALA-treated mice began to decrease and fluctuated in the 5th week [(6.40 ± 0.35) mmol / L], and the fasting blood glucose level in the 5-ALA treatment group was (6.02 ± 0.17) mmol / L] was lower than that of the control group [(6.54 ± 0.05) mmol / L] (P <0.05). Real-time PCR results showed that 5-ALA inhibited the overexpression of XBP-1s in adipose tissue due to obesity (2- △△ CT was 0.029 ± 0.017 in 5-ALA group, 0.029 ± 0.006), P <0.05; western blotting also showed that the level of XBP-1s in 5-ALA-treated mice was lower than that in the control group. [Conclusion] 5-ALA may alleviate the endoplasmic reticulum stress level and improve blood glucose metabolism in mice by inhibiting the IRE1-XBP-1 pathway of ER stress pathway in white adipose tissue.