缺氧缺血性脑损伤新生大鼠松果体钟基因表达的变化

Changes of biological clock protein in neonatal rats with hypoxic-ischemic brain damage

摘要:

目的：观察缺氧缺血性脑损伤（hypoxic-ischemic brain damage, HIBD）新生大鼠松果体中CLOCK、BMAL1蛋白表达的变化，探讨钟基因表达异常在HIBD导致的昼夜节律紊乱中的作用。方法：72只7 日龄新生Sprague-Dawley大鼠随机分为假手术组与HIBD模型组，每组36只。采用改良Levine法建立HIBD模型，用Western blot方法测定两组新生大鼠术后0、2、12、24、36、48 h松果体中CLOCK、BMAL1蛋白水平。结果：HIBD模型组松果体的CLOCK及BMAL1蛋白表达水平在HIBD后48 h高于假手术组（P<0.05），在0、2、12、24、36 h CLOCK及BMAL1蛋白表达水平与假手术组相比差异均无统计学意义（P>0.05）。结论：HIBD新生大鼠松果体中CLOCK和BMAL1蛋白在损伤48 h后有显著升高，提示两者可能共同参与缺氧缺血时昼夜节律紊乱的发生。

Abstract:

OBJECTIVE: To study the effects of biological clock protein on circadian disorders in hypoxic-ischemic brain damage (HIBD) by examining levels of CLOCK and BMAL1 proteins in the pineal gland of neonatal rats. METHODS: Seventy-two 7-day-old Sprague-Dawley (SD) rats were randomly divided into sham-operated and HIBD groups. HIBD model was prepared according to the modified Levine method. Western blot analysis was used to measure the levels of CLOCK and BMAL1 in the pineal gland at 0, 2, 12, 24, 36 and 48 hours after operation. RESULTS: Both CLOCK and BMAL levels in the pineal gland increased significantly 48 hours after HIBD compared with the sham-operated group (P<0.05). There were no significant differences in levels of CLOCK and BMAL proteins between the two groups at 0, 2, 12, 24 and 36 hours after operation (P>0.05). CONCLUSIONS: Levels of CLOCK and BMAL1 proteins in the pineal gland of rats increase significantly 48 hours after HIBD, suggesting that both CLOCK and BMAL1 may be involved the regulatory mechanism of circadian disorders in rats with HIBD.