慢性脑低灌注大鼠海马Arc低表达与其认知功能障碍的相关性研究

目的 探讨慢性脑低灌注大鼠海马活性调节的细胞骨架相关蛋白(activity-regulated cytoskeletal-associated protein,Arc)的低表达与其认知功能障碍的相关性。方法 大鼠慢性脑低灌注模型使用持久性双颈总动脉结扎术(2-vessel occlusion,2-VO); 大鼠随机分成假手术组和2-VO组,每组各6只。术后第8周行Morris水迷宫评价其认知功能; 实时定量聚合酶链式反应(Real time quantitative polymerase chain reaction,RT-qPCR)及蛋白免疫印迹法检测大鼠海马Arc mRNA及蛋白表达水平。结果(1)2-VO组大鼠第2～5 d的逃逸潜伏期比假手术组明显延长(P<0.01)及其在原平台区域游泳时间明显比假手术组短(P<0.01);(2)2-VO组大鼠海马Arc mRNA水平及免疫反应条带相对灰度值分别比假手术组明显降低(P均<0.01);(3)空间探索实验中2-VO大鼠在原平台区域游泳时间与海马Arc免疫反应条带相对灰度值呈正相关(r=0.7085,P<0.05)。结论 慢性脑低灌注大鼠的认知功能障碍可能与海马Arc的低表达相关。

The correlation between hippocampal Arc expression and cognitive impairment in rats with chronic cerebral hypoperfusion

ObjectiveTo explore the correlation between the decreased expression of the hippocampal activity-regulated cytoskeletal-associated protein(Arc)and cognitive impairment in rats with chronic cerebral hypoperfusion.Methods The chronic cerebral hypoperfusion rat model was established by permanent 2-vessel occlusion(2-VO, ligation of bilateral common carotid arteries). Rats were randomly divided into sham operation group and 2-VO group(n=6). The cognitive function was evaluated by Morris water maze at 8 weeks after operation. RT-qPCR and Western blot were used to detect the expression of Arc mRNA and protein in hippocampal.Results(1)Compared with the sham operation group, the escape latency from day2 to day 5 was significantly longer(P<0.01), and the swimming time in the original platform area was markedly shorter in rats of 2-VO group(P<0.01).(2)The mRNA and protein levels of Arc in the hippocampus of rats in 2-VO group were dramatically lower than those in the sham operation group, respectively(P<0.01 for all comparisons).(3)The swimming time of rats in the 2-VO group in the original platform area in the spatial probe trial was positively correlated with the expression of Arc.Conclusion The cognitive impairment in rats with chronic cerebral hypoperfusion may be related to the decreased expression of Arc in the hippocampus.