抑制HDAC4对蛛网膜下腔出血早期脑损伤SD大鼠神经行为的影响

Effect of Inhibition of HDAC4 on the Neurological Behavior of SD Rats with Early Brain Injury Induced by Subarachnoid Hemorrhage

目的观察在SD大鼠蛛网膜下腔出血动物模型中,抑制HDAC4对其早期脑损伤的影响。方法40只SD大鼠随机分为空白注射组和药物注射组各20只,于SAH造模前24h分别行侧脑室立体定位注射给药HDAC4抑制剂LMK235,在术前12h、术后12h和术后24h进行神经生物学评分,在术后24~36h行灌注,取出脑组织的额叶和颞叶皮层,利用WesternBlot检测额颞叶组织中H3及Ac-H4K5的表达来反映脑组织的乙酰化水平。结果在14例成功SAH造模的SD大鼠动物模型中(对照组8只,给药组6只),行神经功能缺损评分后进行统计,给药组的分值低于对照组;额叶及颞叶的皮层蛋白经Western Blot检测及分析,给药组的Ac-H4K5较Vehicle组增高,提示组蛋白的乙酰化水平增高;相关性分析提示组蛋白的乙酰化水平与其神经缺损评分分值的大小呈负相关。结论在SD大鼠蛛网膜下腔出血的早期脑损伤动物模型中,抑制HDAC4可改善其神经行为。

Objective To observe the effect of inhibiting HDAC4 on the early brain injury in the animal model induced by SAH in SD rats. Methods 40 SD rats were randomly grouped as Control and Treat, solvent and HDAC4 inhibitor LMK235 were given by lateral-ventricular stereotaxic injection 24 h before the SAH model was conducted, 12 h and 24 h later, the neurological score were assessed. 24 h to 36 h later, the expression of H3 and Ac-H4K5 in frontal and lateral lobe was detected by Western Blot after perfusion and extraction. Results In 14 successful conducted SAH model (Control 8 and Treat 6), the mean score of Treat Group was lower than that of the Control Group;after Western Blot and statistic analysis, the expression of Ac-H4K5 in frontal and lateral lobe were higher in the Treat Group than that in the Control Group;correlation analysis indicated that the level of acetylation of Histone 4 was negatively correlated with the neurological score. Conclusions In the model of early brain injury induced by SAH, inhibiting HDAC4 can improve the neurological behavior.