Caspr敲除在蛛网膜下腔出血早期脑损伤机制的实验研究

Contactin-associated protein knockout activate early brain injury after subarachnoid hemorrhage via apoptosis

目的 探讨黏连蛋白相关蛋白(Caspr)敲除对小鼠蛛网膜下腔出血(SAH)后早期脑损伤(EBI)的影响及其可能的作用机制。方法 采用C57BL/6小鼠及Caspr敲除(Caspr^(+/-))小鼠,共分为4组:SAH模型组、假手术组、Caspr^(+/-)+SAH模型组和Caspr^(+/-)组,采用视交叉前池注血法建立SAH模型。SAH发生24 h后进行神经功能评分和脑水肿检测。采用Western Blot和ELISA法检测Caspr、B淋巴细胞瘤-2基因(Bcl-2)、Bax、Caspase-1、白细胞介素1β(IL-1β)和IL-18的表达;采用TUNEL染色法观察SAH后神经元的凋亡。结果 Caspr敲除导致Bcl-2表达下降,Bax、Caspase-1、IL-1β和IL-18表达升高,促进神经元凋亡。结论 Caspr敲除通过激活神经细胞凋亡加重SAH后的EBI。

Objective To explore the effect of contactin-associated protein(Caspr)knockout on early brain injury(EBI)after subarachnoid hemorrhage(SAH)in mice and its possible mechanism of action.Methods C57BL/7 and Caspr^(+/-)mice were randomly divided into four groups including sham group,SAH model group,Caspr^(+/-)group and Caspr^(+/-)+SAH group.SAH model was established by stereotactic injection of autologous blood into the optic chiasm cistern.Neurological score and brain edema was performed at 24 hours after SAH.The expressions of Caspr,B-cell lymphoma-2(Bcl-2),Bax,Caspase-1,interleukin-1β(IL-1β)and IL-18 were detected by Western blot and ELISA.Neuronal apoptosis after SAH was observed by TUNEL staining.Result Caspr knockout decreased Bcl-2 expression,increased the expression of Bax,Caspase-1,IL-1βand IL-18,and upregulated neuronal apoptosis.Conclusion Caspr Knockout can aggravate the EBI after SAH via activating neuronal apoptosis.