不同缺氧方式对大鼠缺氧诱导因子-1α及脑源性神经营养因子的表达和认知功能影响

发布时间：2018-10-22 17:00

【摘要】：目的阻塞性睡眠呼吸暂停低通气综合征常引起多系统损伤,特别是损伤中枢神经系统,引起认知功能障碍。文中旨在探讨不同缺氧方式下大鼠血清中缺氧诱导因子-1α(HIF-1α)、脑源性神经营养因子(BDNF)水平表达和认知功能的损害及可能相关机制。方法 24只大鼠随机数字表法分为3组:正常对照组,间歇性缺氧组和持续性缺氧组,每组8只。正常对照组大鼠不予任何处理。间歇性缺氧组缺氧舱内循环充入N_2和空气,使箱内氧浓度在(7.0±0.5)%和21%切换,各维持1.5 min,每个循环周期为4 min;持续性缺氧组放入氧浓度为(7.0±0.5)%的缺氧舱内。缺氧组大鼠每天均缺氧8 h,持续30d。记录大鼠体重,ELISA检测血清中HIF-1α、BDNF水平,Morris水迷宫和HE染色分别检测大鼠的行为学和形态学改变。结果正常对照组体重[(218.63±15.29)g]明显高于间歇性缺氧组[(195.75±6.50)g]和持续性缺氧组[(180.88±12.02)g],差异有统计学意义(P0.05)。定位航行实验结果提示间歇性缺氧组和持续性缺氧组逃避潜伏时间明显长于正常对照组(P0.05),间歇性缺氧组逃避潜伏时间较持续性缺氧组明显延长(P0.05)。空间探索实验可知正常对照组穿越平台次数[(4.97±0.47)次]显著多于间歇性缺氧组和持续性缺氧组[(2.63±1.45)次、(3.22±1.30)次],差异有统计学意义(P0.05)。与正常对照组HIF-1α水平、BDNF水平[(14.11±4.06,1 036.40±124.48)pg/mL]比较,间歇性缺氧组[(36.14±9.34)、1 625.34±332.44)pg/mL]、持续性缺氧组[(27.27±6.88,1 204.07±363.81)pg/mL]均明显升高(P0.05),而间歇性缺氧组较持续性缺氧组亦显著升高(P0.05)。HE染色可见持续性缺氧组和间歇性缺氧组CA1区神经元细胞排列分散、紊乱,核膜结构不清,细胞核固缩,细胞质深染,部分细胞破坏。间歇性缺氧组更可见部分细胞缺失和空泡样改变。结论慢性缺氧抑制大鼠生长发育,出现认知功能障碍;慢性间歇性缺氧下高水平的HIF-1α提示机体处于缺氧应激状态,血清BDNF水平代偿性增加可能参与神经元细胞的损伤调节。
[Abstract]:Objective obstructive sleep apnea hypopnea syndrome (OSAS) often causes multiple system damage, especially central nervous system damage and cognitive impairment. The purpose of this study was to investigate the expression of HIF-1 伪 and brain-derived neurotrophic factor (BDNF) in the serum of rats under different hypoxia modes, and to explore the possible mechanism of the impairment of cognitive function. Methods 24 rats were randomly divided into 3 groups: normal control group, intermittent hypoxia group and persistent hypoxia group with 8 rats in each group. Rats in the normal control group were not treated with any treatment. In the intermittent hypoxia group, N _ 2 and air were filled into the hypoxia chamber, and the oxygen concentration was switched between (7.0 卤0.5)% and 21%. The oxygen concentration was (7.0 卤0.5)% in the hypoxia chamber with 4 min; continuous hypoxia for each 1.5 min, cycle. Rats in hypoxia group were exposed to hypoxia for 8 hours per day for 30 days. The body weight of rats was recorded, the levels of HIF-1 伪 and BDNF in serum were detected by ELISA, and the behavioral and morphological changes of rats were detected by Morris water maze and HE staining, respectively. Results the body weight of normal control group [(218.63 卤15.29) g] was significantly higher than that of intermittent hypoxia group [(195.75 卤6.50) g] and persistent hypoxia group [(180.88 卤12.02) g] (P0.05). The results showed that the escape latency time of intermittent hypoxia group and persistent hypoxia group was significantly longer than that of normal control group (P0.05), and the escape latency time of intermittent hypoxia group was significantly longer than that of persistent hypoxia group (P0.05). Space exploration experiment showed that the number of crossing platform in normal control group [(4.97 卤0.47) times] was significantly higher than that in intermittent hypoxia group and persistent hypoxia group [(2.63 卤1.45) times, (3.22 卤1.30) times], the difference was statistically significant (P0.05). Compared with the normal control group, the levels of HIF-1 伪 and BDNF [(14.11 卤4.06) 1 036.40 卤124.48 pg/mL] were compared. Intermittent hypoxia group [(36.14 卤9.34), 1 625.34 卤332.44) pg/mL] and persistent hypoxia group [(27.27 卤6.88) 1 204.07 卤363.81) pg/mL] were significantly increased (P0.05), while intermittent hypoxia group was significantly higher than that of persistent hypoxia group (P0.05). HE staining showed that the neurons in CA1 area of persistent hypoxia group and intermittent hypoxia group were disordered, respectively. The structure of the nuclear membrane is unclear, the nucleus is pyknotic, the cytoplasm is deep stained and some cells are destroyed. Partial cell deletion and vacuolar changes were observed in intermittent hypoxia group. Conclusion chronic hypoxia inhibits the growth and development of rats and leads to cognitive impairment, and the high level of HIF-1 伪 under chronic intermittent hypoxia suggests that the body is in a state of hypoxia stress, and the compensatory increase of serum BDNF level may be involved in the regulation of neuronal cell damage.
【作者单位】：广州中医药大学研究生院;广州军区广州总医院耳鼻喉科;
【基金】：国家自然科学基金(81470702)
【分类号】：R766

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