阻塞性睡眠呼吸暂停综合征致大鼠认知障碍及其机制研究

OSAS-induced cognitive impairment in rats and its mechanism

目的观察大鼠阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome,OSAS)造模后不同时间点空间认知功能和海马NF-κB及Bcl-2表达的变化。方法选择24只雄性SD大鼠,采取随机数字表法,将6只大鼠正常饲养作为正常组,另18只大鼠咽腔注射透明质酸钠凝胶的方法制备OSAS,大鼠造模成功后,根据继续饲养的时间,依次分为2周组、4周组和6周组,每组6只。采用水迷宫监测大鼠空间认知变化,苏木精-伊红染色观察大鼠海马区病理变化,TUNEL检测海马CA1区神经元凋亡,用Western blot检测NF-κB及Bcl-2蛋白表达。结果与正常组比较,2周组、4周组和6周组平均逃避潜伏时间明显延长,穿越平台次数明显减少[(3.8±1.5)次、(4.0±1.4)次和(2.8±0.8次)vs(4.7±1.8)次,P<0.05];海马CA1区凋亡细胞明显增多[(35.2±4.5)个/HP、(57.4±7.3)个/HP和(65.6±5.8)个/HP vs(5.3±0.8)个/HP,P<0.05];NF-κB蛋白表达增多(1.078±0.014、0.965±0.031和0.811±0.336 vs 0.074±0.022,P<0.05),而Bcl-2蛋白表达降低(0.525±0.020、0.716±0.005和0.914±0.031 vs 1.048±0.013,P<0.05),2周组、4周组和6周组两两比较差异均有统计学意义(P<0.05)。结论OSAS可以造成大鼠认知记忆能力下降,NF-κB表达上调及Bcl-2表达下调造成的OSAS大鼠海马神经元凋亡,可能是其认知损伤的重要机制。

Objective To study the spatial cognitive function and expressions of NF-κB and Bcl-2 in hippocampus at different time points after the obstructive sleep apnea syndrome(OSAS)model of rats was established.Methods Twenty-four male SD rats were divided into control group,2-week group,4-week group and 6-week group(6 in each group).The animals in control group were fed on normal forages.An OSAS model was induced by injecting sodium hyaluronate gel into the pharyngeal cavity of rats in 2-week group,4-week group and 6-week group.The spatial cognitive function of rats was monitored by water maze test.The pathological changes in hippocampus were observed with HE staining and the apoptosis of neurons in hippocampal CA1 area was detected with TUNEL staining.The NF-κB and NF-κB protein expressions were detected by Western blot.Results The average time of escape latency was significantly longer while the number of platform-crossing times was significantly smaller in 2-week group,4-week group and 6-week group than in control group(3.8±1.5,4.0±1.4,2.8±0.8 vs 4.7±1.8,P<0.05).The number of apoptic neurons in hippocampal CA1 area was significantly greter and the expression level of NF-κB protein was significantly higher while that of Bcl-2 protein was significantly lower in 2-week group,4-week group and 6-week group than in control group(35.2±4.5/HP,57.4±7.3/HP,65.6±5.8/HP vs 5.3±0.8/HP,P<0.05;1.078±0.014,0.965±0.031,0.811±0.336 vs 0.074±0.022,P<0.05;0.525±0.020,0.716±0.005,0.914±0.031 vs 1.048±0.013,P<0.05).Conclusion OSAS can reduce the spatial cognitive memory in rats.OSAS-induced opoptosis of neurons in hippocampal CA1 area by upregulating the NF-κB expression and downregulating the Bcl-2 expression is one of the important mechanisms underlying the cognitive impairment in rats.