摘要
目的：观察有氧运动对老年大鼠额叶皮层突触密度及与突触丢失和重排密切相关的cofilin和RhoGTPase的影响。方法：1）动物模型的建立：2月龄成年（青年对照组）和24月龄老年雄性Wistar大鼠（随机分为老年安静组、老年低频运动组和老年高频运动组）为研究对象，老年运动组大鼠进行5d的适应性跑台训练（速度10in／rain，坡度0，10—20min／d）。随后按如下运动方案：跑台速度12m／rain，坡度0，60min／d。低频组3d／周，高频组5d／周，共进行12周跑台运动。最后一次训练48h后麻醉取额叶皮层进行相关指标测试。2）尾动脉测量的方法检测大鼠心率、血压；WesternBlot检测皮层RhoA、Racl、Cdc42和CO—filin的蛋白表达；pull—down检测皮层Rael、Cdc42活性；突触素作为突触特异性的标记物，免疫荧光技术检测大鼠皮层突触密度。结果：1）同青年组相比，老年大鼠安静心率、血压明显增加，心脏重量增加，但心脏体重比却下降；12周运动明显改善了老年大鼠上述指标的变化。2）老年大鼠皮层突触密度明显降低，同时cofilin聚集。12周运动显著增加了老年鼠皮层突触密度，降低cofilin的聚集，且高频运动组变化更明显。3）老年大鼠皮层RhoA蛋白表达明显上调，Racl和Cdc42蛋白无明显变化；运动明显下调老年鼠RhoA蛋白的表达，同时使Racl和Cdc42活性明显增强（P〈0．05）。结论：适量运动诱导机体产生良好的整体生物学适应，且运动调节皮层RhoGTPase家族酶活性，抑制皮层cofilin的过度聚集，延缓衰老过程中皮层神经元突触丢失。
Objective ： To investigate the effects of aerobic exercise on the cofilin aggregation and the activity of Rho GTPases associated with synaptic loss at aging prefrontal cortex in rats. Methods：Twenty-four months old male Wistar rats were randomly assigned to a sedentary, a high frequency and a low frequency treadmill exercise group after the familiarization to treadmill exercise for 5 days （ 10 -20min/d at 10m/rain on a 0 slope）. Then exercise groups ran 60 min/day at 12m/rain on a 0% slope for 12 weeks. The low frequency group is 3d/w, the high fre- quency group is 5d/w. Two months male Wistar rats are in control group. All rats were killed 48 h after the last exercise session. Heart rate （HR） and BP were measured with a noninvasive tail-cuff system. The protein expres- sion of eofilin, RhoA, Racl and Cdc42 were detected by Western Blotting and the synapse density with the IF as- sessment, the activity of Racl or Cdc42 with pull-down. Furthermore, Data were analyzed using one-way analysis of variance （ANOVA）. Results ： 1 ） Compared with young adult control group, the resting BP and HR in older a- dults group were significantly higher, the ratio of cardiac to body weight was lower in old sedentary group. These differences were ameliorated after 12 treadmill exercise. 2） The synaptic density was decreased and cofilin was ag- gregated at prefrontal cortex in old rats compared with those in young control group. After 12 weeks aerobic exer- cise, these changes were ameliorated. 3 ） The protein level of RhoA was increased and the activity of Racl or Cdc42 was decreased in aging prefrontal cortex compared to those in young control group. Twelve weeks treadmill exercise induced to a decrease of RhoA and an increase in the activity of Racl or Cdc42. Conclusion： Twelve weeks treadmill running in aging rats augmented the activity of Rho GTPase in prefrontal cortex, resulting in inhib- iting cofilin aggregation and synaptic loss, accompanied with better adaption including lower resting blood pres- sure, heart rate and higher cardiac index. This study provides important insight into mechanisms for explaining how chronic exercise beneficial to age-associated neurodegeneration.
出处
《北京体育大学学报》
CSSCI
北大核心
2013年第11期61-65,69,共6页
Journal of Beijing Sport University
基金
国家自然科学基金资助项目(No.31271278)
国家科技支撑计划课题资助项目(2012BAK21B03)
