酸枣仁汤对REM睡眠剥夺老年大鼠脑神经细胞凋亡及c-fos基因表达水平的影响

Effect of Suanzao-Rentang on Neuronal Apoptosis and c-fos Gene Expression of Aged Rats with Rapid Eye Movement Sleep Deprivation

目的观察酸枣仁汤对快动眼(REM)睡眠剥夺导致的老年大鼠脑皮层和海马部位神经细胞凋亡及cfos基因表达Fos蛋白水平变化的影响。方法将自然衰老24月龄Wistar大鼠随机分成空白对照组(等容生理盐水),老年REM睡眠剥夺组(等容生理盐水),阳性对照组(舒乐安定0.18 mg/(kg·d)),酸枣仁汤低、高剂量组(12.96,25.92 g/(kg·d))。各组灌胃给药2周后,除空白对照组外其余各组用自制改良多平台法剥夺大鼠睡眠48 h制作老年大鼠REM睡眠剥夺模型。通过原位末端标记法(TUNEL)测定各组大鼠大脑皮层和海马部位神经细胞凋亡水平,用免疫组化法检测c-fos基因表达Fos蛋白的水平变化,探讨酸枣仁汤对老年失眠引起的脑神经损害及c-fos基因表达变化的影响。结果与空白对照组比较,老年REM睡眠剥夺组大鼠脑皮层和海马部位神经凋亡细胞增多,Fos蛋白表达明显增高。与老年REM睡眠剥夺组比较,酸枣仁汤组脑神经凋亡细胞及Fos蛋白表达明显下降,但仍高于正常对照组。结论c-fos基因很可能参与了老年大鼠REM睡眠剥夺后的细胞凋亡过程,酸枣仁汤可能是通过抑制脑组织c-fos基因表达上调,抑制神经细胞凋亡而发挥脑保护作用。

Objective To observe the effect of Suanzao-Rentang on neuronal apoptosis and c-fos gene expression in Fos protein levels in cortex and hippocampus of aged rats with rapid eye movement （REM） sleep deprivation. Methods Natural aging 24 months old Wistar rats were randomly divided into control group （isovolumetric saline） ,REM sleep deprivation elderly group （ isovolumetric saline）, positive control group estazolam 0.18mg/（ kg · d）, Suanzao-Rentang low and high dose group 12.96,25.92 g/（ kg · d）. Each group was given intragastfic administration for two weeks, then each group except the control group is made REM sleep deprivation for 48h to produce model of old rats with homemade improved multi-platform. The nerve cells apoptosis of cortex and hippocampus in the rats from each group are determined by situ end labeling （TUNEL） and level changes in c-fos gene expression to Fos protein are detected by using immunohistochemistry and explore the effect of suanzao- Rentang on the nerve damage and c-fos gene expression change in elder, which caused by insomnia. Results Compared with the control group, the cerebral cortex and hippocampus nerve cells apoptosis of rats, which are from REM sleep deprivation group, increased, and their Fos protein expression was significantly. Compared with REM sleep deprivation older group, Suanzao-Rentang groups nerve cells apoptosis and Fos protein expression in brain significantly decreased,but still higher than the normal control group. Conclusion C-fos gene is likely involved in the process of apoptosis in old REM sleep deprivation rats and Suanzao- Rentang inhibit neuronal apoptosis and play a protective role in the brain possibly by inhibiting brain upregulation of c-fos gene.