摘要
目的:研究L-丝氨酸对大鼠永久性脑梗死的神经保护作用、治疗剂量及有效治疗时间窗,并探讨相关作用机制。方法:制作大鼠永久性大脑中动脉栓塞(pMCAO)模型,腹腔注射L-丝氨酸,通过神经行为学评分、脑梗死体积测定和尼氏染色法,观察L-丝氨酸的治疗剂量效应(56 mg/kg、168 mg/kg和504 mg/kg治疗组)和治疗时间窗(1 h、3 h、6 h、12 h和24 h治疗组);并测定丝氨酸消旋酶抑制剂对L-丝氨酸疗效的影响。利用激光多普勒血流监测仪观察缺血区血供及L-丝氨酸对缺血区局部脑血流量的影响。结果:与pMCAO组相比,L-丝氨酸于pMCAO后3 h使用,168 mg/kg和504 mg/kg两个剂量都能较好地降低神经行为学评分,减少脑梗死体积,抑制海马CA1区神经细胞的丢失。在治疗时间窗的研究中,L-丝氨酸在pMCAO后6 h内治疗具有明显的神经保护作用,12 h及以后使用,神经保护作用不明显。丝氨酸消旋酶抑制剂不改变L-丝氨酸的疗效。脑缺血30 min时注射L-丝氨酸可明显增加缺血区局部脑血流量,并且这一作用不受甘氨酸受体阻断剂士的宁的影响。结论:L-丝氨酸对永久性脑梗死具有神经保护作用,其机制可能部分与增加缺血区皮质的血供有关。
AIM：To investigate the neuroprotective effect,therapeutic dosage and time window of L-serine against permanent cerebral injury in rats.METHODS：Permanent middle cerebral artery occlusion（pMCAO） was induced in the rats to determine the efficacy of L-serine（ip） by neurological evaluation,TTC staining and Nissl staining. L-serine was used at different doses（56 mg/kg,168 mg/kg and 504 mg/kg） and for different time periods（1 h,3 h,6 h,12 h and 24 h after pMCAO）.Aminooxyacetic acid（AOAA ）,an inhibitor of serine racemase,was used to alter the efficacy of L-serine.Laser Doppler perfusion monitor was used to observe the regional cerebral blood flow（rCBF） in the ischemic cerebral cortex under the condition with or without L-serine treatment.RESULTS：Treatment with L-serine at doses of 168 mg/kg and 504 mg/kg at time point of 3 h after pMCAO greatly decreased the neurological deficit score and infarct volume,and attenuated the loss of hippocampal CA1 neuronal cells.In the observation of therapeutic time window, L-serine displayed a significant neuroprotective effect if used within 6 h after pMCAO,but did not exert any notable effect if used over 12 h after pMCAO.AOAA hardly changed the effect of L-serine.L-serine treatment notably raised rCBF in the area of ischemic cerebral cortex when it was injected 30 min after pMCAO.However,strychnine,an antagonist of strychnine-sensitive glycine receptor,did not alter this effect of L-serine.CONCLUSION;L-serine has neuroprotective effect on permanent ischemic brain injury in rats if administered early and sufficiently by augmentation of rCBF in the ischemic cerebral cortex.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2012年第3期470-477,共8页
Chinese Journal of Pathophysiology
基金
国家自然科学基金青年基金资助项目(No.8100497)
关键词
L-丝氨酸
永久性大脑中动脉栓塞
脑血流
L-serine
Permanent middle cerebral artery occlusion
Brain blood flow
