Panobinostat改善SD大鼠蛛网膜下腔出血后早期脑损伤的观察

Observation of panobinostat alleviates early brain injury in subarachnoid hemorrhage model

目的观察在SD大鼠蛛网膜下腔出血动物模型中,Panobinostat抑制HDAC(LBH589)对早期脑损伤的作用。方法SD大鼠按随机数字表法分为假手术组(10只)、出血组(10只)、出血+Vehicle组(20只),出血+Panobinostat注射组和药物注射组(20只),于SAH造模前24 h分别行侧脑室立体定位注射给药,在术前12 h、术后12 h和24 h分别进行神经功能损伤评分,然后取半球脑组织测脑水含量,或者进行灌注,取出脑组织的额叶和颞叶皮层,利用免疫印迹(Western Blot)检测H3及Ac-H3K27的乙酰化水平。结果假手术组和出血组的神经功能损伤评分均高于对照组,差异有统计学意义(F=13.000,P=0.007);出血组脑水含量显著高于假手术组,差异有统计学意义(F=8.229,P=0.019)。在成功SAH造模的SD大鼠进行分组,给药组额叶及颞叶皮层组织中的Ac-H3K27水平较Vehicle组增高,差异有统计学意义(F=41.250,P=0.000);给药组脑水含量较Vehicle组下降,差异有统计学意义(F=8.211,P=0.020);给药组较Vehicle组的神经损伤评分下降,差异有统计学意义(F=9.560,P=0.011);相关性分析表明H3组蛋白的乙酰化水平(Ac-H3K27)与其神经缺损评分分值呈负相关(r=-0.585,P=0.046)。结论在SD大鼠蛛网膜下腔出血的早期脑损伤动物模型中,Panobinostat抑制HDAC可显著改善神经行为,缓解脑损伤。

Objective To observe the effect of panobinostat (LBH589) on the early brain injury (EBI) in the model of subarachnoid hemorrhage(SAH) in SD rats. Methods SD rats were randomly divided into 4 groups: sham(10 rats) and SAH(10 rats), SAH+ vehicle(20 rats) and SAH+ Panobinostat(20 rats). Drug or vehicle was given by lateral-ventricular stereotaxic injection 24h before the SAH model was introduced.Water contents and the neurological scores were determined at 24h post-SAH.The levels of Ac-H3K27 in frontal and lateral lobe were detected by Western blot. Results The mean neurological score of the SAH group was higher than that of the sham group(F=13.000, P=0.007). The water content of the SAH group was higher than that of the sham group (F=8.229, P=0.019). The level of Ac-H3K27 was higher in the SAH+ Panobinostat group than that in the SAH+ vehicle group(F=41.250, P=0.000). The mean neurological score of the SAH+ Panobinostat group was lower than that of the SAH+ vehicle group(F=9.560, P=0.011). The water content of the SAH+ Panobinostat group was lower than that of the SAH+ vehicle group(F=8.211, P=0.020). The correlation analysis indicated that the level of acetylation of H3 was negatively correlated with the neurological score(r=-0.585, P=0.046). Conclusion Panobinostat can improve the neurological behavior and alleviate early brain injury in the SAH model.