摘要
目的 探讨人尿激肽原酶(HUK)对大鼠局部脑缺血再灌注后缺血侧皮质巢蛋白的表达及空间学习记忆能力障碍的作用。方法60只大鼠按随机数字表法分为5组:假手术组、脑缺血组、HUK低剂量组(3.5×100PNAU/kg)、HUK中剂量组(8.75×100PNAU/kg)和HUK高剂量组(17.5×10^3PNAU/kg),线栓法制作大鼠大脑中动脉阻塞再灌注模型,HUK治疗组于术后2周内腹腔注射HUK。第15天开始各组大鼠采用Morris水迷宫装置评价大鼠的空间学习记忆能力,免疫组化染色检测缺血侧皮质巢蛋白的表达。结果脑缺血组大鼠在定向航行试验和空间探索试验中均表现出明显的空间认知功能障碍。在定向航行试验中.HUK中、高剂量治疗组大鼠平均逃避潜伏期与缺血组比较明显缩短,差异有统计学意义(P〈0.05)。在空间探索试验中,HUK中、高剂量治疗组大鼠原平台象限停留时间百分比以及穿过原平台位置次数均大于脑缺血组.比较差异有统计学意义(P〈0.05)。缺血侧皮质巢蛋白免疫组化染色结果显示,HUK中、高剂量治疗组大鼠缺血侧皮质巢蛋白的吸光度值明显高于脑缺血组,比较差异有统计学意义(P〈0.05)。结论HUK可以明显改善大鼠局部脑缺血再灌注后的空间学习记忆能力.其机制可能与HUK增加缺血侧皮质巢蛋白的表达,促进神经再生有关。
Objective To investigate the effects of human urinary kallidinogenase (HUK) on the abilities of spatial learning and memory and the expression of nestin in the peri-infarction cortex of rats after focal cerebral ischemia-reperfusion. Methods Sixty rats were equally randomized into 5 groups: sham-operated group, model group, low dose HUK treatment group (3.5 ×10^-3 PNAU/kg), median dose HUK treatment group (8.75×10^-3 PNAU/kg) and high dose HUK treatment group (17.5×10^-3 PNAU/kg). The focal cerebral ischemia-reperfusion models in the model group and HUK treatment groups were established by introducing an intraluminal filament into the right middle cerebral artery of the rats. HUK was administered intraperitoneally right after the operation and afterward once daily for 2 weeks. The spatial learning and memory functions were studied by Morris water maze test, and the nestin expression in the peri-infarction cortex was measured by immunohistochemistry on the 15th d. Results The model group exhibited seriously spatial learning and memory deficits in both place navigation trail and spatial probe trial. In the place navigation trial, the mean values of escape latency in the median dose and high dose HUK treatment groups were shorter than those in the model group (P〈0.05). In the spatial probe trial, significant differences in the percentages of time spending in the former platform quadrant and frequency of crossing the former platform site were noted between the model group and both median dose and high dose HUK treatment groups (P〈0.05). Immunohistochemical analysis showed that the nestin expression in the peri-infarction cortex of median dose and high dose HUK treatment groups increased significantly as compared with that in the model group (P〈0.05). Conclusion Treatment with HUK improves the spatial learning and memory abilities in rats after focal cerebral ischemia-reperfusion, which may result from the increasing expression ofnestin and the proliferation of neural stem cells.
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2010年第10期1001-1004,共4页
Chinese Journal of Neuromedicine
关键词
人尿激肽原酶
脑缺血再灌注
空间学习记忆
Human urinary kallidinogenase
Cerebral ischemia-reperfusion
Spatial learning and memory