盐酸法舒地尔对慢性脑低灌注损伤大鼠海马细胞的保护作用

Neuroprotective effects of hydroxy fasudil on brain hippocampal neurons damage of chronic cerebral hypoperfusion rat model

目的观察Rho激酶抑制剂盐酸法舒地尔(hydroxy fasudil,HF)对慢性低灌注脑缺血所致大鼠海马神经细胞损伤的保护作用。方法采用永久性结扎大鼠双侧颈总动脉(permanent occlusion of the bilateral CCA,2VO)制备大鼠慢性不完全性全脑缺血模型,将SD大鼠随机分为假手术组、脑缺血模型组和HF治疗组,运用Morris水迷宫行为学方法检测大鼠空间学习记忆能力;用HE染色观察海马组织形态学改变。结果 Morris水迷宫检测发现模型组大鼠学习记忆能力受损,与假手术组比较逃避潜伏期延长、空间辨别能力下降;组织学观察模型组大鼠海马CA1细胞发生丢失,组织结构异常。连续给予盐酸法舒地尔30 d能改善大鼠学习记忆功能,减少脑缺血所致的大鼠海马神经细胞丢失。结论盐酸法舒地尔可减少慢性脑缺血所致的大鼠海马神经元的丢失,改善学习记忆功能。

Objective To observe the neuroprotective effects of hydroxy fasudil （HF）, a Rho-kinase inhibitor, on hippocampal neurons damage after chronic cerebral hypoperfusion in a rat model. Methods Chronic cerebral hypoperfusion in rats was performed by permanent occlusion of the bilateral common carotid artery （2VO）. SD rats were divided into three groups., sham-operated group, ischemic group and HF treated group （10 mg/kg）. Morris water maze wasused to measure spatial learning and memory performance. HE stain was used to observe morphology change. Results Compare with sham-operation group, 2V0 rats resulted in spatial learning and memory impairments shown by longer escape latency and shorter time spent in the target quadrant. Morphological observe of 2V0 rats hippocampal show CA1 neurons lost. Administration of hydroxy fasudil （10 mg/kg, once per day for 30days） can improve 2V0 rats learning and reduce the neuron lost. Conclusions Long-term administration of hydroxy fasudil markedly attenuated chronic cerebral hypoperfusion induced neuronal damage.