丹参酮IIA对局灶性脑缺血大鼠的神经保护作用及其机制初探

Neuroprotective effects of tanshinone IIA on vascular dementia in rats

目的:探讨丹参酮II A对局灶性脑缺血大鼠的神经保护作用及其机制。方法:大鼠局灶性脑缺血模型采用持续性大脑中动脉线栓法制作而成。丹参酮II A剂量2mg/kg.d,4mg/kg.d ip。持续栓塞3 h后进行神经行为学评分,6 h后断头取脑,分离皮层和化海马组织,分光光度法测定丙二醛(malondialdehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)以及谷胱甘肽过氧物酶(GPX)活性的变化;运用高效液相色谱法测定不同组大鼠皮层和海马组织内谷氨酸和γ-氨基丁酸的含量。结果:①缺血组动物均有不同程度的神经功能缺损,评分均在3分以上,而丹参酮IIA治疗组动物检测提尾时不能伸展对侧前肢,评分均为为2分以下,与缺血组动物比较有显著差异;②丹参酮II A可减少MDA的生成,增加SOD、GPX活性;③持续栓塞6h后,大鼠皮层和海马组织谷氨酸和γ-氨基丁酸的含量增加,丹参酮II A可减少局灶性脑缺血大鼠皮层和海马组织内谷氨酸和γ-氨基丁酸的含量。结论:丹参酮II A在局灶性脑缺血大鼠可发挥神经保护作用,其可能的作用机制包括抗氧化作用以及对兴奋性氨基酸和抑制性氨基酸的调节作用。

Objective：To investigate the underlying neuroprotective mechanisms of Tanshinone IIA（TSA） on rat cerebral ischemia in vivo.Methods： Study of TSA on rat cerebral ischemia in vivo： Male SD rats were divided into four groups（sham-operated,ischemic and treated group（lower dose and higher dose））.Before ischemia impairment,TSA（2mg/kg.d,4mg/kg.d） was administrated by i.p.for one week in treated group.Permanent middle cerebral artery occlusion（pMCAO） was introduced as an in vivo ischemic model.A nylon suture was inserted into internal carotid artery to occlude the beginning of middle cerebral artery.After 3 h pMCAO,neurology deficit score was evaluated.At the point of 6 h,all animals were decapitated.Levels of malondialdehyde（MDA）,activity of superoxide dismetase（SOD） and glutathione peroxidase（GPX） in brain tissue were detected by spectrophotometer;High-performance liquid chromatography（HPLC） with fluorescence detection was applied to measure the contents of glutamate and gamma-aminobutyric acid（GABA） in cortex and hippocampus.Results： TSA can improve neurological deficit score in ischemic rats;An elevation of SOD and GPX activity and decrease of MDA level were shown in TSA treated group after brain ischemia;Increased glutamate and gamma-aminobutyric acid induced by brain ischemia were markedly inhibited by TSA pretreatment.Conclusions： The neuroprotective effect of TSA are partly due to its functions as follow： anti-free radical injury;regulating the content of glutamate and gamma-aminobutyric acid.