丹参酮Ⅱ_A对血管性痴呆大鼠的神经保护作用机制

Neuroprotective effects of tanshinone Ⅱ_A on vascular dementia in rats

目的:初步探讨丹参酮主要成分丹参酮ⅡA对血管性痴呆大鼠的神经保护作用机制。方法:大鼠血管性痴呆模型采用永久性结扎大鼠双侧颈总动脉制作而成。动物随机分为假手术组、缺血模型组、丹参酮ⅡA(2,4 mg.kg-1.d-1)治疗组。持续缺血30 d后开始观测各组的学习记忆功能,然后断头取脑,分离皮层和海马组织,分光光度法测定丙二醛(MDA)含量和超氧化物歧化酶(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:丹参酮IIA可以改善血管性痴呆大鼠的学习记忆功能;丹参酮IIA可减少MDA的生成,增加SOD,GPX活性;慢性缺血30 d后,大鼠皮层和海马组织谷氨酸和γ-氨基丁酸的含量减低,丹参酮ⅡA可增加血管性痴呆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ⅡA在血管性痴呆大鼠可发挥抗氧化作用并调节兴奋性氨基酸和抑制性氨基酸的含量。

Objective： To investigate the underlying neuroprotective mechanisms of Tanshinone ⅡA（TSA） on rat cerebral ischemia in vivo.Method： 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）.Chronic cerebral ischemmia after permanent bilateral carotid artery ligation was introduced as an in vivo ischemic model.After ischemia impairment,TSA（2,4 mg·kg-1·d-1） was administrated by ip for 30 days in treated group.We used morris water maze to investigate the learning and memory.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.Result： TSA can improve learning and memory deficits in vascular dementia.An elevation of SOD and GPX activity and decrease of MDA level were shown in TSA treated group after brain ischemia.Decreased glutamate and gamma-aminobutyric acid induced by chronic brain ischemia were markedly inhibited by TSA pretreatment.Conclusion： 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.