高原环境对大鼠肝脏糖异生的影响

Impact of high-altitude exposure on hepatic gluconeogenesis in rats

目的研究海拔4300 m高原环境对大鼠肝脏糖异生的影响及机制。方法健康成年大鼠36只,随机分为平原对照组(C组)、高原暴露1、3、7、15、30 d组(分别为H1、H3、H7、H15、H30组)。应用RT-PCR方法测定肝组织中葡萄糖-6-磷酸酶(G6Pase)、转录因子叉头框蛋白O1(Fox O1)的mRNA表达水平以及应用Western Blot法检测其蛋白表达水平,应用分光光度法测定肝糖原含量,使用自动生化分析仪检测血糖水平。多组间比较采用方差分析,进一步两两比较采用Tukey检验。结果与C组比较,(1)H1、H3和H7组肝组织中G6Pase的表达水平以及肝糖原含量显著增高(P值均<0.05);(2)Fox O1的表达水平在H3、H7、H15及H30组中明显降低(P值均<0.05);(3)各高原组血糖水平无明显变化。结论高原暴露急性期肝脏糖异生及糖原合成活跃,可能是高原习服的机制之一;腺苷酸活化蛋白激酶(AMPK)和Fox O1对高原暴露大鼠肝脏糖异生具有调节作用;糖原含量增加可能抑制了AMPK的活性。

Objective To study the effect of high altitude （HA） of 4300 m on the hepatic gluconeogenesis in rats and its underlying mechanism. Methods Thirty - six healthy aduh male Sprague - Dawley （SD） rats were randomly assigned to group H1 （ HA exposure for 1 day, n = 6）, group H3 （ HA exposure for 3 days, n = 6）, group H7 （ HA exposure for 7 days, n = 6）, group HI5 （ HA exposure for 15 days, n = 6）, group H30 （HA exposure for 30 days, n = 6）, and group C （no HA exposure, n = 6）. After the treatment, the mRNA and protein levels of glucose -6 -phosphatase （G6Pase）, and forkhead box transcription factor O1 （FoxO1） in the hepatic tissues were determined by RT - PCR and Western blot, respectively. The content of hepatic glycogen was determined by spectrophotometry, and the blood glucose level was measured using an automatic biochemical analyzer. The one - way analysis of variance （ ANOVA ） was used to analyze the differences between groups, and the Tukey test was further used to compare the differences between two groups. Results Compared with those in group C, the levels of G6Pase and glycogen in the hepatic tissues of rats increased significantly in groups H1, H3, and H7 （ P 〈 0.05 ）, and the expression level of FoxO1 decreased significantly in groups H3, H7, H15, and H30 （P 〈0.01 ）. No significant differences in the concentration of blood glucose were observed between the HA - treated groups. Conclusion Increased hepatic gluconeogenesis and glycogen synthesis in the early phase of HA exposure may be one of the important mechanisms of HA acclimatization. FoxO1 and AMPK are involved in the regulation of hepatic gluconeogenesis. The increased content of hepatic glycogen is associated with the decreased activity of AMPK.