人血白蛋白对实验性蛛网膜下腔出血后认知功能的改善作用

摘要

Objective To investigate whether human serum albumin (ALB) can improve long-term cognitive function in SAH rats.Methods Eighty adult male SD rats weighing 270-320 g were randomly divided into sham operation group and normal saline,low ALB dose (0.63 g/kg) and high ALB dose (1.25 g/kg) treatment groups (20 in each group).Endovascular perforation model was used to induce SAH.Working and spatial memory of SAH rats were evaluated by novel object recognition (NOR) and Morris water maze (MWM) respectively.Spine density and synapserelated proteins levels were measured by immunoblotting with Golgi staining.Results The shortterm and long-term working memory were significantly better in both low and high ALB dose treatment groups (P=0.001).Compared with normal saline treatment group,the latency and swimming distance were significantly shorter (P=0.015,P=0.019;P=0.015,P=0.017),while the frequency to cross quadrant was significantly higher (P=0.018,P=0.027) in low and high ALB dose treatment groups.The spine density was significantly higher in hippocampal area in low dose treatment group (P=0.025),while both cortical and hippocampal spine densities were significantly higher in high dose group than in saline group (P=0.026,P=0.016).The expression levels of synapse-related proteins were significantly higher in both low and high ALB dose treatment groups.Conclusion ALB can significantly improve cognitive functions in SAH rats by upregulating spine density and synapse-related proteins levels.%目的 探讨静脉即刻给予人血白蛋白(ALB)是否对蛛网膜下腔出血(SAH)远期认知功能预后具有改善作用.方法 选取270～320 g成年SD 2月龄雄性大鼠80只,随机分为假手术组、生理盐水组、低剂量组(ALB 0.63g/kg)和高剂量组(ALB 1.25 g/kg),每组20只.采用血管刺破方法建立大鼠SAH模型.在建模后29d开始进行认知功能评估,采用新事物认知实验进行短时和长时工作记忆能力测试;Morris水迷宫实验进行空间记忆能力评价;高尔基染色和蛋白印迹实验检测树突棘密度及突触相关蛋白表达.结果 低、高剂量组大鼠短时和长时工作记忆能力都较生理盐水组大鼠明显提高(P=0.001).与生理盐水组比较,低、高剂量组大鼠第3天潜伏期(P=0.015,P=0.019)和第4、5天游泳距离(P=0.015,P=0.017)明显缩短,穿越原平台位置次数显著提高(P=0.018,P=0.027).与生理盐水组比较,低剂量组显著提高海马区树突刺密度(P=0.025);高剂量组显著提高皮质及海马区树突棘密度(P=0.026,P=0.016);低、高剂量组大鼠突触相关蛋白表达水平明显提高(P＜0.05).结论 ALB可能通过提高SAH大鼠树突棘密度和突触相关蛋白含量,促进认知功能恢复.