慢性间歇低氧-复氧对大鼠糖、脂代谢及AQP7表达的影响  

Impact of chronic intermittent hypoxia-reoxygenation on glucose and lipid metabolism and the expression of aquaporin 7 in rats

作　　者：高立 魏翠英[1] Gao Li;Wei Cuiying(Department of Geriatric Medicine,the First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014000,China)

机构地区：[1]内蒙古科技大学包头医学院第一附属医院老年医学科,包头014000

出　　处：《国际呼吸杂志》2024年第11期1241-1249,共9页International Journal of Respiration

基　　金：国家自然科学基金(81660020);内蒙古自治区科技计划(2021GG0219)。

摘　　要：目的观察慢性间歇低氧(CIH)及复氧状态下大鼠糖、脂代谢的变化及大鼠脂肪、肾脏、骨骼肌组织中水通道蛋白7(AQP7)的表达水平, 探讨AQP7在CIH致胰岛素抵抗(IR)中的作用。方法本研究为实验研究。按照随机数字表法, 将40只6周龄雄性SD大鼠分为对照组和实验组, 每组各20只。对照组置于常氧环境饲养12周;实验组连续8周每天8 h置于间歇低氧舱中, 模拟人类重度睡眠呼吸暂停(阻塞性睡眠呼吸暂停低通气综合征)状态, 然后常氧饲养4周, 模拟持续气道正压通气治疗状态。2组分别于0、8、12周取内眦静脉血检测空腹血糖(FBG)、空腹胰岛素(FINS)、甘油三酯、胆固醇, 并留取脂肪、肾脏、骨骼肌组织进行病理观察和AQP7检测。结果 (1)基线时, 2组大鼠各观察指标差异均无统计学意义(均P>0.05)。(2)8周时, 实验组大鼠FBG、稳态模型胰岛素抵抗指数(HOMA-IR)高于对照组, 甘油三酯水平低于对照组(均P<0.05), 胆固醇水平与对照组比较差异无统计学意义(P>0.05)。复氧4周后, 实验组大鼠FBG、HOMA-IR回落, 甘油三酯上升, 胆固醇水平无明显变化, 与对照组比较差异均无统计学意义(均P>0.05)。(3)8周时, 实验组大鼠脂肪、肾脏的AQP7表达低于对照组(均P<0.05), 骨骼肌的AQP7表达高于对照组(P<0.05)。复氧4周后, 实验组大鼠脂肪、肾脏AQP7表达与对照组比较差异均无统计学意义(均P>0.05), 骨骼肌AQP7表达低于对照组(P<0.05)。(4)蛋白质印迹结果显示, 8周时实验组大鼠骨骼肌AQP7表达高于对照组, 复氧4周后低于对照组(均P<0.01)。结论 (1)CIH是IR的原因之一;(2)CIH可能导致糖、脂代谢异常;(3)CIH状态下AQP7在脂肪、肾脏组织中表达下降, 复氧后恢复至对照组水平, 而在骨骼肌组织中表达的变化与脂肪和肾脏相反, AQP7在胰岛素敏感组织中的变化提示其可能介导了CIH所致IR的调节。Objective:To explore the changes in glucose and lipid metabolism in rats under conditions of chronic intermittent hypoxia(CIH)and reoxygenation,as well as the expression levels of aquaporin 7(AQP7)in rat adipose tissue,kidney,and skeletal muscle;and to explore its role in CIH-induced insulin resistance(IR).Methods:This study was an experimental study.Forty six-week-old male Sprague-Dawley(SD)rats were randomly divided into two groups according to a random number table method:the normal control group(NC group)and the test group(T group),with 20 rats in each group.Rats in the NC group were raised in a normoxic environment for 12 weeks;and those in the T group were placed in an intermittent hypoxia chamber for 8 hours per day and 8 consecutive weeks to simulate the state of severe obstructive sleep apnea-hypopnea syndrome(OSAHS),and then raised in a normoxic environment for 4 weeks to simulate ventilation treatment of continuous positive airway pressure(CPAP).Blood samples were taken from the tail veins of both groups at 0,8,and 12 weeks to measure fasting blood glucose(FBG),fasting insulin,triglycerides(TG),and cholesterol(CHO).Tissues of adipose,kidney,and skeletal muscle were also collected for pathological observation and detection of AQP7 expression.Results:(1)At baseline,there were no significant differences in the observed indicators between the two groups(all P>0.05);(2)At 8 weeks,the T group showed significantly higher FBG and homeostatic model assessment for insulin resistance(HOMA-IR),but lower TG levels than the NC group(all P<0.05).CHO was comparable between groups(P>0.05).After 4 weeks of reoxygenation,FBG and HOMA-IR levels returned to normal,TG levels increased,and CHO levels remained unchanged in the T group,with no significant differences compared to the NC group(all P>0.05).(3)At 8 weeks,the expression of AQP7 in adipose and kidney tissues of the T group was significantly downregulated compared to the NC group,but which significantly upregulated in skeletal muscle(all P<0.05).After 4 weeks of reox

关 键 词：慢性间歇低氧 复氧 胰岛素抵抗 水通道蛋白7 

分 类 号：R766[医药卫生—耳鼻咽喉科]