2019 年第 6 期 第 14 卷

慢性间歇低氧作用下小鼠肝脏组织中缺氧诱导因子2α的表达及其对脂质代谢的影响

Effect of chronic intermittent hypoxia on expression of gypoxia inducible factor-2α and lipid metabolism

作者：王越王悦蒋宏峰刘倍倍陈蕾蕾吴小凡

英文作者：

单位：100029首都医科大学附属北京安贞医院心内科北京市心肺血管疾病研究所（王越、王悦、刘倍倍、陈蕾蕾、吴小凡），心血管生物学研究室（蒋宏峰）

英文单位：

关键词：脂质代谢；慢性间歇低氧；缺氧诱导因子2α

英文关键词：

• 摘要：

• 【摘要】目的    探讨慢性间歇低氧（CIH）环境下小鼠肝脏组织中缺氧诱导因子（HIF）2α的表达变化及对肝脏脂质代谢的影响。方法    选择无特定病原体级载脂蛋白E基因敲除雄性小鼠24只，适应性喂养1周后随机分为3组，各8只。对照组普通饲料喂养；高脂组给予高脂饲料喂养12周；高脂+低氧组于高脂饲料喂养4周后，将小鼠放入低氧舱内8 h/d，持续8周。12周后取小鼠肝脏组织，通过油红O染色法计算油滴面积占总面积的百分比，酶法检测肝脏组织中三酰甘油和总胆固醇含量，免疫组织化学染色法检测HIF-2α的表达，应用超氧化物阴离子探针检测活性氧含量。结果    高脂+低氧组肝脏组织中脂滴面积占总面积的百分比高于高脂组和对照组［（35.52±12.77）%比（11.65±7.43）%、（0.45±0.26）%］，总胆固醇和三酰甘油含量高于高脂组和对照组，HIF-2α表达水平和活性氧含量高于高脂组和对照组［（45.0±6.3）%比（17.7±2.5）%、（5.2±2.4）%，（23.74±5.19）%比（4.33±2.11）%、（0.25±0.11）%］,差异均有统计学意义（均P<0.05）。结论    HIF-2α在CIH诱导的肝脏脂质代谢紊乱中发挥重要作用，其对氧化应激反应的调控作用可能是引起肝脏脂质蓄积的重要通路，HIF-2α有望成为防治肝脏脂质代谢异常的重要靶点。

• 【Abstract】Objective    To observe the expression of hypoxia inducible factor(HIF)-2α in liver tissue under chronic intermittent hypoxia(CIH) and explore the influence of CIH on liver lipid metabolism. Methods    Twenty-four specific-pathogen-free apolipoprotein-E-/- mice were randomly divided into control group (n=8), high-fat diet group(n=8) and high-fat diet+CIH group(n=8). The control group was fed with normal diet; the high-fat diet group had high-fat feed for 12 weeks; the high-fat diet+CIH group was fed with high-fat diet for 4 weeks and placed in hypoxic chamber 8 h/d for 8 weeks. Liver tissue was separated after 12 weeks treatment; lipid area was determined by oil red O staining; contents of triglyceride and total cholesterol were tested by enzymatic method; expression of HIF-2α was detected by immunohistochemistry and active oxygen was detected by dihydroethidium fluorescent staining. Results    Percentage of oil area in high-fat diet+CIH group was greater than that in high-fat diet group and control group［（35.52±12.77）% vs （11.65±7.43）%,（0.45±0.26）%］; contents of triglyceride and total cholesterol in high-fat diet+CIH group were higher than those in high-fat diet group and control group; expression of HIF-2α and content of active oxygen in high-fat diet+CIH group were higher than those in high-fat diet group and control group［（45.0±6.3）% vs （17.7±2.5）%,（5.2±2.4）%; （23.74±5.19）% vs （4.33±2.11）%,（0.25±0.11）%］; the differences were significant(all P<0.05). Conclusions    HIF-2α plays an important role in CIH-induced hepatic lipid metabolism disorder, its regulation on oxidative stress may be a pathway for lipid accumulation. HIF-2α is expected to be an important target in preventing and treating liver lipid metabolism disorder.