利鲁唑对大鼠蛛网膜下腔出血后早期脑损伤的保护作用

Neuroprotective effect of riluzole against early brain injury after subarachnoid hemorrhage in rats

目的研究利鲁唑对蛛网膜下腔出血(SAH)大鼠早期脑损伤的保护作用。方法 91只大鼠分为假手术组24只、安慰剂组34只和治疗组33只。假手术组仅切断颈外动脉并结扎;安慰剂组和治疗组建立大鼠颈内动脉穿刺SAH模型,治疗组术后2 h经腹腔注射0.5 ml利鲁唑(6 mg/kg),安慰剂组注射等量生理盐水。采用改良Garcia评分系统评估大鼠神经功能,伊文思蓝渗出法评估血-脑脊液屏障通透性,干湿重法测定脑含水量,Western印迹法及免疫荧光染色检测皮质谷氨酸转运体1(GLT-1)表达,试剂盒测定脑脊液谷氨酸含量及皮质中丙二醛(MDA)、谷胱甘肽水平,TUNEL法检测神经元凋亡。结果与安慰剂组比较,治疗组大鼠SAH后神经功能评分显著提高(P<0.05),伊文思蓝含量、脑含水量、脑脊液中高浓度谷氨酸及皮质中MDA含量均明显降低(P<0.05),皮质中GLT-1表达及还原型谷胱甘肽水平显著升高(P<0.05), TUNEL/NeuN复染阳性细胞显著减少(P<0.05)。结论利鲁唑可减轻SAH后早期脑损伤,其机制可能与抗谷氨酸兴奋性和抑制神经元凋亡有关。

Objective To study the protective effect of riluzole against early brain injury after subarachnoid hemorrhage(SAH).Methods Ninety-one rats were randomly divided into the sham group with 24 rats, the placebo group with 34 and the treatment group with 33. External carotid artery was cut and ligated in the sham group, SAH models of internal carotid artery puncture were established in the placebo group and treatment group. Riluzole( 0. 5 ml) was used via intraperitoneal injection 2 h after surgery in the treatment group and saline(0.5 ml) in the placebo group. The neurological function was assessed by modified Garcia score. The permeability of blood brain barrier( BBB) was assessed by Evans blue extravasation method. The brain water content was determined by the wet-dry method. Glial glutamate transporter 1( GLT-1) expression was detected by Western blotting and immunofluorescence. The glutamate level in the cerebrospinal fluid(CSF) and malondialdehyde(MDA) and glutathione(GSH) in the cortex were measured with Kit, and the neuronal apoptosis was detected by TUNEL staining. Results Compared with the placebo group, the neurological function was significantly improved(P<0.05), the Evens blue content, brain water content, glutamate in the CSF and MDA expression in the cortex reduced obviously, GLT-1 and GSH content in the cortex significantly increased( P<0. 05), and the positive cell of TUNEL/NeuN counterstaining decreased significantly(P<0.05). Conclusion Riluzole can alleviate early brain injury after SAH, and the potential mechanism may relate with anti-glutamate and anti-apoptosis effects.