摘要
目的 探讨胆碱酯酶抑制剂———石杉碱甲对新生大鼠缺氧缺血性脑损伤 (hypoxia ischemiabraindamage ,HIBD)智能缺陷的改善和保护作用。方法 将HIBD模型鼠随机分为安慰剂组(n =11)、小剂量石杉碱甲组 ( 0 0 5mg/kg ,n =12 )、大剂量石杉碱甲组 ( 0 1mg/kg,n =12 )和对照组(n =10 ,为假手术组动物 )。以Morris水迷宫成绩判断大鼠学习、记忆功能变化 ;以结扎侧纹状体、皮层、海马损失面积和海马CA1区锥体细胞密度变化及乙酰胆碱酯酶组化染色判定脑组织损伤程度。结果 HIBD后 5周安慰剂组大鼠的学习、记忆功能受损严重 ,水迷宫实验潜伏期 (找到平台时间 )较对照组延长 ( 44s与 3 0s,P <0 0 5 ) ,平台撤除象限搜索时间缩短 ( 14s与 40s,P <0 0 1) ,脑组织损失面积最重 ;而与安慰剂组相比大剂量石杉碱甲治疗明显减轻大鼠的学习、记忆功能障碍 (潜伏期 :3 4s与 44s ,P <0 0 5 ;搜索时间 :3 5s与 14s,P <0 0 1) ,脑组织损失面积较轻 ,小剂量石杉碱甲治疗组大鼠学习、记忆功能改善不明显 (潜伏期 :45s与 44s,P >0 0 5 ;空间搜索时间 :17s与 14s,P >0 0 5 ) ,脑组织损失面积也较重 ;大鼠学习、记忆功能缺陷与海马CA1区锥体细胞密度呈显著相关 (r=0 777,P <0 0 1)。
Objective To investigate the protective effects of Huperzine A, a potent acetylcholinesterase inhibitor, against the hypoxic ischemic brain damage (HIBD) of the cognitive and morphology in the neonatal rats. Methods Postnatal 7 days old rats were given vehicle or Huperzine A (0.05 mg/kg or 0.1 mg/kg, i.p.) following HIBD (unilateral carotid artery ligation followed by hypoxia) or sham operation, and then tested the learning ability and memory in the Morris water maze (MWM) from 36 to 40 postnatal days. The performance in MWM (escape latency, probe time) were recorded to evaluate the learning and memory dysfunction. At the end of MWM trials, the rats were decapitated and their brains were histologically analyzed. The tissue loss in different brain regions including striatum, cortex, and hippocampus were analyzed by image analysis system. The CA 1 subfield neurons numbers were counted to evaluate the brain damage. The acetylcholinesterase histochemistry staining was used to determine the activity of acetylcholinesterase in different brain regions. Results Compared with sham-operated group, HIBD rats with the vehicle treatment displayed significant tissue losses in the hippocampus (including CA 1 neurons), cortex, and striatum, as well as severe spatial memory deficits (escape latency: 44 s vs 30 s, P<0.05, probe time: 14 s vs 40 s, P<0.01). Huperzine A treatment (0.1 mg/kg) resulted in significant protection against both HI-induced brain tissue losses and spatial memory impairments (mean escape latency: 34 s vs 44 s, P<0.05, probe time: 35 s vs 14 s,P<0.01). However, Huperzine A treatment (0.05 mg/kg) did not show any significant improvement of spatial memory impairments (mean escape latency: 45 s vs 44 s, P>0.05, probe time:17 s vs 14 s,P>0.05),but moderate to severe brain tissue losses. There was a pronounced reduction of CA 1 neuron density in ipsilateral hemisphere of vehicle-treated group and 0.05 mg/kg Huperzine A group compared with contralateral hemisphere or ipsilateral hemisphere of sham-operated group and 0.1 mg/kg Huperzine A group ( 72 vs 232, P<0.01, 72 vs 229, P<0.01, respectively). There was a close linear correlation between the CA 1 neurons cell number and the mean escape latency for 5 d acquisition trials (r=0.777, P<0.01). Conclusion The unilateral HI brain injury in a neonatal rat model was associated with cognitive deficits, and that Huperzine A treatment may be protective against both brain injury and spatial memory impairment. Huperzine A showed a therapeutic potential for the treatment of hypoxic-ischemic encephalopathy (HIE) caused by the perinatal asphyxia.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2003年第1期42-45,共4页
Chinese Journal of Pediatrics
基金
国家"九五"医学科技公关项目 ( 96 90 4 0 6 0 4)
