辛醇对大鼠脑缺血再灌注后星形胶质细胞和胶质原纤维酸性蛋白的影响

摘要

目的 观察辛醇对大鼠脑缺血再灌注后星形胶质细胞及胶质原纤维酸性蛋白(GFAP) 表达的影响,探讨辛醇脑保护的可能机制.方法 取48只健康成年雄性SD大鼠,随机分为假手术组、模型组、溶剂对照组和辛醇干预组,每组12只.假手术组不造模,其余3组采用线栓法制作大鼠大脑中动脉缺血再灌注损伤模型,缺血时间为2 h,再灌注时间为24 h.辛醇干预组于缺血前30 min按5 mmol /kg体质量腹腔注射辛醇溶液,溶剂对照组于缺血前30 min腹腔注射等容积5％ 二甲基亚砜溶液,假手术组及模型组于同时腹腔注射等容积0.9％氯化钠注射液.各组大鼠处死前均进行神经功能缺损评分; 尼氏染色法观察神经细胞损伤情况; 免疫组织化学及蛋白质印迹法检测缺血半暗带GFAP的表达.结果 缺血再灌注24 h后,模型组神经功能缺损评分明显高于假手术组[(2.8 ± 0.4) 分比0分](P < 0.05); 溶剂对照组神经功能缺损评分[(2.8 ± 0.4) 分]与模型组比较差异无统计学意义(P > 0.05); 辛醇干预组神经功能缺损评分[(1.1 ± 0.4) 分]明显低于模型组(P < 0.05) .缺血再灌注24 h后,模型组缺血半暗带GFAP阳性细胞数明显多于假手术组(P < 0.05); 溶剂对照组缺血半暗带GFAP阳性细胞数与模型组比较差异无统计学意义(P > 0.05) .辛醇干预组缺血半暗带GFAP阳性细胞数明显少于模型组(P < 0.05) .缺血再灌注24 h后,假手术组缺血半暗带GFAP蛋白表达较少,模型组GFAP蛋白表达量明显增多,溶剂对照组与模型组相比无明显差异,而辛醇干预组GFAP蛋白表达量明显少于模型组.结论 抑制星形胶质细胞活化可能是辛醇发挥脑保护作用的机制之一.%Objective To observe the effect of octanol on astrocytes and the expression of glial fibrillary acidic protein (GFAP ) after cerebral ischemia-reperfusion in rats and to explore the possible protective mechanisms of octanol. Methods Forty-eight healthy adult male SD rats were randomly divided into sham operation group,model group,solvent control group and octanol group,with 12 rats in each group. Model group, solvent control group and octanol group were made models of middle cerebral artery ischemia(2 h) -reperfusion (24 h) injury by thread embolization. At 30 minutes before ischemia,octanol group was intraperitoneally injected 5 mmol /kg octanol solution; solvent control group was injected the same volume of 5％ dimethyl sulfoxide solution; sham operation group and model group had 0.9％ sodium chloride injection. Neurological deficit score was assessed before execution. Neuronal damage was observed by Nessler staining. GFAP expression in ischemic penumbra was detected by immunohistochemistry and western blotting. Results After reperfusion(24 h) ,neurological deficit score in model group was significantly higher than that in sham operation group[(2.8 ± 0.4) vs 0](P <0.05); there was no significant difference between solvent control group[(2.8 ± 0.4) ] and model group(P >0.05); the score in octanol group[(1.1 ± 0.4) ] was significantly lower than that in model group(P < 0.05). After reperfusion(24 h) ,the number of GFAP-positive cells in model group was significantly more than that in sham operation group (P < 0.05 ). There was no significant difference of the number of GFAP-positive cells between solvent control group and model group (P > 0.05). The number of GFAP-positive cells in octanol group was significantly less than that in model group (P < 0.05). After reperfusion(24 h) ,expression of GFAP protein decreased in sham operation group and increased in model group; there was no significant difference between solvent control group and model group; expression of GFAP protein in octanol group was significantly lower than that in model group. Conclusion Octanol can inhibit the activation of astrocytes and protect brain against ischemia-reperfusion injury.