人血清白蛋白对大鼠蛛网膜下腔出血后血脑屏障及神经功能的影响

Effects of human albumin on the blood-brain barrier and behavior changes in subarachnoid hemorrhage rats

目的:探讨人血清白蛋白对于蛛网膜下腔出血(SAH)后血脑屏障及行为学的影响。方法:将雄性大鼠随机分为假手术组、生理盐水组、低剂量人血清白蛋白治疗组(0.63g/kg)和高剂量白蛋白治疗组(1.25g/kg)。采用刺破法制造大鼠SAH模型,利用改良Garcia评分系统及平衡木实验评估SAH后24 h及14 d行为学的变化,利用伊文思蓝外渗和Ig G染色评估血脑屏障破坏情况,以蛋白免疫印迹法观察基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶-9(MMP-9)的表达情况。结果:与生理盐水组相比较,低剂量和高剂量白蛋白治疗组大鼠SAH后24 h及14 d神经功能缺损评分及平衡木评分均明显降低(P<0.05),伊文思蓝渗出均减少(P<0.05),血管周围lg G渗出均减少,患侧组织中MMP-2及MMP-9的表达均明显减少(P<0.05),且低剂量和高剂量白蛋白治疗效果无明显差异(P>0.05%)。结论:SAH后给予白蛋白治疗,可以降低MMP-2及MMP-9的表达,减轻出血继发的血脑屏障的破坏,改善神经功能缺损。

Objective： To investigate the effect of albumin therapy on blood-brain barrier and behavior. Methods：Male rats were divided into four groups： sham operation group, saline group, low dose of albumin therapy group （0.63 g/kg） and high dose of albumin therapy group（ 1.25 g/kg）. SAH was induced by the endovascular perforation rat model. Neu- rological outcomes were assessed by a blinded observer at 24 h and 14 d post SAH using the modified garcia score and beam balance test. The blood-brain barrier disruption was assessed by evans blue content analysis and IgG staining. Western blot was used to determine the expression of MMP-2 and MMP-9. Results：Compared with saline group, the neu- rological outcomes of SAH rats were improved upon both low and high dose of albumin therapy at 24 h and 14 d post SAH. Both the content of Evans blue and the IgG staining were decreased. Western bolt showed the reduced expression of MMP-2 and MMP-9 in low and high dose of albumin group. There are not significant difference between low dose of albu- min group and high dose of albumin group. Conclusion： Albumin therapy can decrease the expression of MMP-2 and MMP-9, reduce BBB disruption, and thereby improve neurological outcomes in subarachnoid hemorrhage rats.