低氧训练时心肌组织细胞低氧诱导因子1α与凋亡相关蛋白的表达

Association between hypoxia inducible factor-1 alpha and apoptosis-related proteins in the myocardial tissues under hypoxic training

背景:运动对心肌细胞凋亡的影响有了比较多的研究,但低氧训练对心肌细胞凋亡的研究不多见。低氧诱导因子1α是否控制了Bcl-2家族的表达而影响凋亡发生,尚未明确。目的:分析低氧训练时心肌组织低氧诱导因子1α蛋白表达情况与凋亡蛋白的相互关系。方法:将健康雄性SD大鼠60只,随机分为6组:(1)对照组常温常氧下喂养,不运动。(2)低氧组在低氧环境下喂养,不运动。(3)运动组常温常氧下运动。(4)低住高练组常氧下居住,低氧、常氧训练交替进行。(5)高住低练组低氧下居住,常氧下训练。(6)高住高练低练组低氧下居住,低氧、常氧训练交替进行。运动组大鼠负荷跑台训练8周,训练每周6 d,运动速度和运动时间连续递增,运动速度从开始的10 m/min、持续时间为15 min递增至第8周的25 m/min、持续时间为50 min。低氧程度由开始从海拔1 500 m增加到第8周达到海拔3 600 m。训练结束后,运用苏木精-伊红染色、TUNEL法和蛋白免疫组织化学方法检测大鼠心肌组织细胞低氧诱导因子1α、Bcl-2、Bax的表达变化。结果与结论:(1)常氧时低氧诱导因子1α几乎不表达,低氧可增加低氧诱导因子1α的蛋白表达,低氧复合运动,表达更多。(2)低氧组和低氧运动组大鼠心肌组织Bax表达变化不是很明显,但Bcl-2表达就远远低于常氧不运动组。(3)低氧组、运动组与低氧运动组心肌组织细胞凋亡较明显,但三者相互之间比较差别较小,说明低氧结合运动不会使细胞凋亡更加严重。结果表明各实验组Bcl-2表达显著低于对照组,Bax表达变化不明显。但低氧可增加低氧诱导因子1α的蛋白表达,低氧复合运动,表达更多。说明低氧诱导因子1α有可能调节Bcl-2、Bax的表达,从而控制细胞凋亡的发生与否。

BACKGROUND： There are many comparative studies addressing the effect of exercise on apoptosis of cardiomyocytes, but few of them are reported on myocardial apoptosis after hypoxic training. It is unclear whether hypoxia-inducible factor 1α has some effects on cell apoptosis through controlling the expression of Bcl-2 family. OBJECTIVE： To investigate the relationship between the hypoxia-inducible factor 1α and apoptosis-related protein in the cardiomyocytes during hypoxic training. METHODS： Sixty male healthy Sprague-Dawley rats were randomly divided into six groups： feeding at room temperature under normoxia and no training（control group）; feeding at room temperature under hypoxia and no training（hypoxia group）; normoxic training at room temperature（training group）; feeding under normoxia＋hypoxic training alternating with normoxic training; feeding under hypoxia and normoxic training; feeding under hypoxia＋hypoxic training alternating with normoxic training. Rats in the exercise group were subjected totreadmill training under loading for 8 weeks, 6 days a week. The moving speed and time were increased from 10 m/min and 15 minutes to 25 m/min and 50 minutes at the 8th week, respectively. Hypoxia degree was increased from 1 500 meters above sea level to 3 600 meters above sea leave at the 8th week. After training, hematoxylin-eosin staining, TUNEL method and western blot assay were used to detect the expressions of hypoxia-inducible factor 1α, Bcl-2 and Bax in the myocardial tissues of rats. RESULTS AND CONCLUSION： Under normoxia, hypoxia-inducible factor 1α rarely expressed; while the expression of hypoxia-inducible factor 1α increased under hypoxia, especially under hypoxic training. Compared with the control group, Bax expression in the myocardial tissues had no changes in the hypoxia group and hypoxic training group, but Bcl-2 expression in these two groups was significantly lowered. Apoptosis in the myocardial tissues was obvious in the hypoxia, training and hypoxic training groups, but no significant difference was found among the three groups. These findings indicate that hypoxic training is unable to increase cell apoptosis and hypoxia-inducible factor 1α can control the cell apoptosis by regulating Bcl-2 and Bax expression.