低氧和复氧对大鼠糖脂代谢的影响及其作用靶点的研究

Effect of hypoxia on glycolipid metabolism and the exploration of target genes at tissue level in rat model

目的探讨慢性持续性低氧和复氧对大鼠糖脂代谢和不同组织中低氧诱导因子1α(HIF-1α)、核转录因子κB(NF-κB)和腺苷酸活化蛋白激酶(AMPK)mRNA表达的影响。方法建立慢性低氧大鼠模型,随机分为7组:常氧3周、6周、12周对照组,低氧3周、6周组和复氧6周、12周组,每组各8只。比较各组血糖、血脂水平和不同组织中HIF-1α、NF-κB和AMPK的表达情况。结果 (1)低氧6周组FPG低于常氧6周组[(3.52±0.59)vs(8.80±1.64)mmol/L,P<0.01];复氧6周组FPG高于低氧6周组[(7.20±2.2)vs(3.52±0.59)mmol/L,P<0.05],与常氧6周组比较,差异无统计学意义。(2)低氧组TC、TG、HDL-C水平低于常氧组(P<0.01),复氧后TC和HDL-C可恢复至常氧水平。低氧组LDL-C、FFA水平高于常氧组(P<0.01),且在复氧后可完全恢复至常氧水平。(3)低氧组皮下脂肪组织中HIF-1α、NF-κB和AMPK mRNA表达水平高于常氧组[(276.87±2.77)vs(100±4.03),(184.41±2.17)vs(100±1.56),(259.88±3.03)vs(100±2.95),P<0.05]。结论慢性持续性低氧可导致大鼠血糖、血脂的改变,复氧可使其恢复至正常水平。大鼠皮下脂肪组织中HIF-1α、NF-κB和AMPK等基因的表达可能在上述过程中发挥了一定的作用。

Objective To investigate the effect of long-term and chronic hypoxia on glycolipid metabolism and the exploration of target genes at tissue level in rats. Methods 56 male wistar rats were randomly divided into seven groups：normoxia-3 weeks group,hypoxia-3 weeks group,normoxia-6 weeks group,hypoxia-6 weeks group,reoxygenation-3 weeks group,normoxia-12 weeks group,reoxygenation-12 weeks group,8 in each group.After hypoxia treatment,fasting blood glucose and blood lipid were measured.The expression of hypoxia induced factor-1α（HIF-1α）、nuclear factor-kappa B（NF-κB）and Adenosine 5‘-monophosphate-activated protein kinase（AMPK）mRNA in rat liver、subcutaneous fat、brown fat、visceral fat and skeletal muscle were detected. Results（1）The fasting plasma glucose（FPG）level in hypoxia-6 group significantly decreased compared with that in normoxia-6 group[（3.52±0.59）vs（8.80±1.64）mmol/L,P〈0.01],the index significantly increased in reoxygenation-6 group compared to that in hypoxia-6 group[（7.20±2.2）vs（3.52±0.59）mmol/L,P〈0.05]and showed no significant difference compared with normoxia-6 group,indicating that it returned completely to the normoxia level.（2）The blood cholesterol（TC）、triglyceride（TG）and high-density lipoprotein（HDL-C）level in hypoxia group significantly decreased compared with normoxia group（P〈0.01）,the level of TC and HDL-C significantly increased in reoxygenation-6 group compared to that in hypoxia-6 group（P〈0.01）and showed no significant difference compared with normoxia-6 group,indicating that it returned completely to the normoxia level.The low-density lipoprotein（LDL-C）level and free fatty acid（FFA）level significantly increased compared with normoxia-6 group（P 0.01）and returned completely to normoxia level in reoxygenetion-6 group.（3）The expressions of HIF-1α、NF-κB and AMPK mRNA in subcutaneous fat in hypoxia group was significantly increased compared with normoxia group [（276.87±2.77）vs（100±4.03）,（184.41±2.17）vs（100±1.56）,（259.88±3.03）vs（100±2.95）,P〈0.05]. Conclusion Long-term and chronic hypoxia may influence the fasting blood glucose and lipid level,and reoxygenation could recover the changes.The expressions of HIF-1α、NF-κB and AMPK mRNA may be involed in this process.