脑卒中大鼠神经炎症反应和胶质细胞活化与认知功能的相关性研究

Correlation between neuroinflammatory response,glial cell activation and cognitive function in stroke rats

目的观察脑卒中大鼠神经炎症反应、胶质细胞活化与认知功能的相关性,探讨神经炎症反应、胶质细胞活化对脑卒中大鼠认知功能的影响。方法将60只健康雄性SD大鼠随机数字表法分为A组、B组和C组,各30只。A组大鼠采用线栓阻断大脑中动脉法制备缺血再灌注大鼠模型。B组大鼠仅操作到暴露分离颈总动脉、颈外动脉。C组大鼠不做任何处理。分别于处理前,处理后7、14、21 d测量3组大鼠神经功能缺损评分。处理后1个月时采用Morris水迷宫测量3组大鼠认知功能,随后处死大鼠取脑组织,采用蛋白质印迹法检测脑组织中白细胞介素(IL)-6、干扰素、胶质原纤维酸性蛋白(GFAP)、离子钙结合衔接分子1(Iba-1)表达情况。结果A组大鼠处理后7、14、21 d时的Longa评分和Bederson评分均显著高于建模前,差异均有统计学意义(P<0.05)。3组大鼠1-5 d的逃避潜伏期均呈显著减少趋势,不同时间点比较差异均有统计学意义(P<0.05)。B组和C组大鼠同一天逃避潜伏期均显著少于A组大鼠,差异均有统计学意义(P<0.05),但B组和C组比较差异无统计学意义(P>0.05)。A组、B组和C组大鼠平台穿越次数分别为(2.67±0.67)、(6.33±1.33)、(6.67±0.93)次,B组和C组大鼠平台穿越次数显著高于A组,差异均有统计学意义(P<0.05)。B组和C组大鼠脑组织IL-6、干扰素、GFAP和Iba-1相对吸光度均显著低于A组,差异均有统计学意义(P<0.05),但B组和C组比较差异均无统计学意义(P>0.05)。Perason相关性分析结果表明,第5天逃避潜伏期与大鼠脑组织IL-6、干扰素、GFAP和Iba-1相对吸光度均呈显著正相关性(r=0.604、0.585、0.691、0.725,P<0.05),平台穿越次数与大鼠脑组织IL-6、干扰素、GFAP和Iba-1相对吸光度均呈显著负相关性(r=-0.628、-0.591、-0.720、-0.753,P<0.05)。结论脑卒中大鼠认知功能显著降低,与神经炎症反应增强、胶质细胞活化密切相关。

Objective To observe the correlation between neuroinflammatory response,glial cell activation and cognitive function in stroke rats,and to explore the effects of neuroinflammatory response and glial cell activation on cognitive function in stroke rats.Methods Sixty healthy male SD rats were divided into group A,group B and group C according to the random number table method,with 30 rats in each group.In group A,the rat model of ischemia-reperfusion was established by blocking the middle cerebral artery with thread plug.Group B rats were only exposed to separate the common carotid artery and external carotid artery.Group C rats were not treated.The neurological deficit scores of the three groups were measured before treatment and 7,14 and 21 days after treatment.One month after treatment,the cognitive function of the three groups of rats was measured by Morris water maze.Then the rats were killed and the brain tissues were taken.The expressions of interleukin-6(IL-6),interferon(IFN),glial fibrillary acidic protein(GFAP)and ionic calcium binding adaptor molecule 1(Iba-1)in the brain tissues were detected by Western blotting technique.Results The Longa score and Bederson score of rats in group A at 7,14 and 21 days after treatment were significantly higher than those before modeling,the differences were statistically significant(P<0.05).The escape latency of rats in the three groups decreased significantly from 1 to 5 d,and the differences were statistically significant at different time points(P<0.05).The escape latency of rats in group B and group C on the same day was significantly shorter than that in group A,and the difference was statistically significant(P<0.05),but there was no statistically significant difference between group B and group C(P>0.05).The platform crossing times of rats in group A,group B and group C were(2.67±0.67),(6.33±1.33)and(6.67±0.93)times,respectively.The platform crossing times of rats in group B and group C were significantly higher than those in group A,and the differences were statistically significant(P<0.05).The relative absorbances of IL-6,interferon,GFAP and Iba-1 in the brain tissue of the rats in groups B and C were significantly lower than those in group A,and the differences were statistically significant(P<0.05),but there were no statistical significance differences between groups B and C(P>0.05).The results of perason correlation analysis showed that the escape latency on the 5th day was significantly positively correlated with the relative absorbance of IL-6,IFN,GFAP and Iba-1 in rat brain(r=0.604,0.585,0.691,0.725;P<0.05),and the number of platform crossings was significantly negatively correlated with the relative absorbance of IL-6,IFN,GFAP and Iba-1 in rat brain(r=-0.628,-0.591,-0.720,-0.753;P<0.05).Conclusion The cognitive function of stroke rats decreased significantly,which was closely related to the enhancement of neuroinflammatory response and glial cell activation.