短暂性脑缺血再灌注损伤对老年大鼠认知功能及海马神经元凋亡的影响

EFFECTS OF TRANSIENT CEREBRAL ISCHEMIA-REPERFUSION INJURY ON COGNITIVE FUNCTION AND APOPTOSIS OF HIPPOCAMPAL NEURONS IN AGED RATS

目的探讨短暂性脑缺血再灌注损伤对老年大鼠认知功能及海马神经元凋亡的影响。方法老年雄性Wistar大鼠60只,随机分为脑缺血1min组(A组)、脑缺血5min组(B组)和假手术组(C组),各20只。用Pulsineli方法建立全脑缺血模型。3组分别于再灌注12h和再灌注3d处死10只大鼠,应用TUNEL法检测海马神经元凋亡,Morris水迷宫实验评价认知功能。结果 A组及C组再灌注12h和再灌注3d有少量神经元凋亡,两组TUNEL阳性细胞计数比较差异无显著性(P>0.05);B组再灌注12h和再灌注3d神经元凋亡计数较A组、C组明显增加,差异有显著性(F=17.44,P<0.01);B组再灌注3d神经元凋亡明显增加,与再灌注12h比较差异有显著性(t=3.05,P<0.05)。水迷宫检测结果显示,与A组和C组比较,B组大鼠再灌注12h和再灌注3d逃避潜伏期和学习潜伏期明显延长(F=29.84、34.11,P<0.01)。B组再灌注12h和再灌注3d逃避潜伏期和学习潜伏期差异无统计学意义(P>0.05)。A组与C组比较,再灌注12h和再灌注3d逃避潜伏期和学习潜伏期差异无显著性(P>0.05)。结论短暂性脑缺血5min即可造成老年大鼠神经元凋亡增加、出现认知功能障碍。

Objective To investigate the effects of transient cerebral ischemia （TCI）-reperfusion injury on cognitive function and apoptosis of hippocampal neurons in aged rats. Methods Sixty aged healthy male Wistar rats were evenly radomized to three groups as group A （ischemia 1 min group）, group B （ischemia 5 min group） and group C （sham-operation group）. A model of global cerebral ischemia was created by using Pusinelli＇s method. The rats in the three groups were sacrificed after 12 h and three days of reperfusion, 10 rats in each time respectively. The apoptosis of neuroal cells in hippocampus was detec- ted by TUNEL. Morris water maze experiment was employed to assess the cognitive function. Results The number of apoptosis was much increased in group B, after reperfusion for 12 h and three days, as compared with that in groups A and C （F = 17.44, P〈0.01）. The difference of apoptosis between 12 h-reperfusion and 3 d-reperfusion in group B was significant. In groups A and C, apoptosis was noted in a few of neurons after reperfusion for 12 h and three days, and the difference of TUNEL-positive cells be- tween the two groups was not significant （P〉0.05）. Morris water maze detection displayed that compared with groups A and C, after reperfusion for 12 h and three days, the escape response latency and learning latency period of rats in group B were markedly extended （t = 3.05 ,P〈0.05）. In group B, the difference of escape response latency and learning latency period between 12 h reper- fusion and 3 d reperfusion was not significant （P〉0.05）, in groups A and C, the difference of that was also not significant （P〉 0.05）. Conclusion Transient cerebral ischemia of 5 minutes may increase the apoptosis of neurons in aged rats, leading to cogni- tive dysfunction.