慢性间歇性低氧对老年大鼠血压和心肌线粒体氧化应激的影响

The effects of chronic intermittent hypoxia on blood pressure and myocardial mitochondrial oxidative stress in aged rats

目的探讨慢性间歇低氧对老年大鼠血压、交感神经活动、线粒体氧化应激状态的影响。方法建立慢性间歇低氧（CIH）大鼠模型，根据年龄不同以随机数字表法将84只雄性Wistar大鼠（3-4月龄和23-24月龄）分为4组。分别为青年对照组、青年CIH组、老年对照组和老年CIH组，CIH暴露3周，比较各组大鼠动脉压、颈动脉窦神经动作电位频率、肺功能差异，检测血浆中的儿茶酚胺、乌头酸酶／延胡索酸酶活性比值（A／F）、组织中的超氧化物歧化酶（SOD）水平。结果青年CIH组动脉血压比青年对照组增高[（150．4±25．6）mmHg（1mmHg=0．133kPa）比（102．2±7．4）mmHg，P〈0．01]，老年CIH组[（132．8±16．2）mmHg]与老年对照组动脉血压[（127．1±26．8）mmHg]比较差异无统计学意义；与青年对照组比较，老年对照组通气量下降[（331．7±53．5）ml·min^-1·kg^-1比（554．8±111．9）ml·min^-1·kg^-1，P〈0．05]，老年CIH组[（354．1±51．9）ml·min^-1·kg^-1]与老年对照组通气量[（331．7±53．5）ml·min^-1·kg^-1]比较差异无统计学意义；比较低氧刺激不同年龄组颈动脉窦神经动作电位频率变化，老年对照组小于青年对照组[（6．2±5．5）倍比（11．8±6．6）倍，P〈0．01]，老年CIH组小于青年CIH组[（22．2±13．5）倍比（44．2±12．1）倍，P〈0．01]；血浆上甲肾上腺素、肾上腺素水平青年CIH组较青年对照组更高[（39．0±8．9）nmol／L比（20．8±10．6）nmol／L、（48．1±13．6）nmol／L比（26．7±14．3）nmol／L,均P〈0．05]，老年对照组与青年对照组比较老年CIH组与老年对照组比较差异均无统计学意义；青年CIH组较青年对照组A／F降低[（0．26±0．13）比（0．58±0．04），P〈0．01]，老年对照组较青年对照组减少[（0．29±0．02）比（0．58±0．04）．P〈0．01]，老年对照组和老年CIH组比较差异无统计学意义；青年CIH组较青年对照组SOD下降[（5．30±0．90）NU／mgprot比（6．10±1．73）NU／mgprot，P〈0．05}，老年对照组和老年CIH组SOD比较差异无统计学意义。结论CIH对老年大鼠诱发高血压的影响与青年时期不同．表现为老年大鼠交感神经过度活动降低和线粒体氧化应激减轻，提示老化可能抑制了CIH影响血压的两个重要致病机制，降低了CIH对血压的不良影响。

Objective To investigate the effect of chronic intermittent hypoxia on blood pressure,sympathetic nerve activity and myocardial mitochondrial oxidative stress status in aged rats. Methods Chronic intermittent hypoxia（CIH）rat models were established. A total of 84 male Wistar rats（3-4 and 23-24 months old, respectively）were randomly and equally divided into four groups according to age： young control group, young CIH group, aged control group and aged C/H group. CIH exposure lasted for 3 weeks. The arterial blood pressure, the frequency of carotid sinus nerve action potential, the lung function, the levels of catecholamine, aconitase/fumarate ratio （A/F）, plasma superoxide dismutase（SOD）in the plasma were measured and compared between four groups. Results The arterial blood pressure was significantly higher in young CIH group than in the young control group[（150.4±25.6）mmHg vs. （102.2±7.4）mmHg,P〈0.01]. There was no significant difference in the arterial blood pressure between the aged CIH group[（132.8±16.2）mmHg]and the aged control group[（127. 1±26.8）mmHg）.The minute volume ventilation was significantly lower in the aged control group than in young control group[（331.7±53.5）ml·min^-1·kg^-1 vs. （554.8＋111.9）ml·min^-1·kg^-1 P〈0.05）. The min^-1·kg^-1 ventilation showed no significant difference between the aged CIH group[（354.1±51.9）ml - inin i . kg ＇land the aged control group[（331.7±53.5）ml - min J - kg t＇3. The rate of CSN frettuency change by hypoxia stimulation was lower in the aged control group than in young control group[（6.2±5.5）times us. （11.8±6.6）times,P%0.01] ,and was lower in the aged CIH group than in the young CIH group （（22.2±13.5） times vs. （44.2± 12. 1） times,P〈0. 011. The levels of plasma norepinephrine and epinephrine were higher in the young CIH group Ihan in the control group（（59.0±8.9）nmol/L vs. （20.8±10.6）nmol/L, （48. 1± 13.6）nmol/L us. （26.7 ±14.3）nmol/L, both P〈0.05]. The levels of plasma norepinephrine and epinephrine showed no significant difference between the aged control group and the young control group, also no significant difference was found between the aged CIH group and the aged control group. The A/F ratio was lower in the young CIH group than in the young control group（（0.26±0. 13） vs. （0.58±0.04） ,P〈0. 01）. The A/F ratio was lower in tile aged control group than in the young control group [（0.29±0.02）vs. （0.58±0.04）, P〈0.01],but there was no significant difference in the A/F ratio between the aged CIH group and the aged control group. The level of SOD was significantly lower in the young CIH group than in the young control group[（5.30±0.90） NU/mgprot vs. （6. 10±1.73） NU/mgprot P〈0.05）. There was no significant difference in SOD level between aged control group and aged CIH group. Conclusions The effect of CIH on blood pressure in aged rats is different from the youth rats. This study shows adeereasedsympathetic nervous over activity and a reducedmitochondrial oxidative stress in aged rats. Aging probably suppresses two important pathogenic mechanisms, by which CIH affects blood pressure, therefore releases CIH induced blood pressure abnormalily.