丹参酮IIA对血管性痴呆小鼠神经保护作用机制浅谈.docVIP

丹参酮IIA对血管性痴呆小鼠神经保护作用机制浅谈 　【摘要】 目的初步探讨丹参酮主要成分丹参酮IIA对血管性痴呆小鼠的神经保护作用机制。方法双侧颈总动脉反复缺血/再灌注合并尾部放血降压方法建立血管性痴呆小鼠模型。动物随机分为假手术组、缺血模型组、丹参酮IIA低、高剂量（4 mg/kg.d，8 mg/kg.d ）治疗组。手术20 d后开始运用Morris水迷宫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(malondialdehyde, MDA) 含量和超氧化物歧化酶(superoxide dismutase, SOD)以及谷胱甘肽过氧化物酶（GSH-Px）活性的变化；运用高效液相色谱法测定不同组小鼠皮层和海马组织内谷氨酸和γ-氨基丁酸的含量。结果①丹参酮IIA可以改善血管性痴呆小鼠的学习记忆功能； ②丹参酮IIA可减少MDA的生成, 增加SOD、GSH-Px活性; ③小鼠手术20 d后，小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可增加血管性痴呆小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在血管性痴呆小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。 【关键词】 丹参酮IIA; 谷氨酸; γ-氨基丁酸； 血管性痴呆 　　Abstract：ObjectiveTo investigate the underlying neuroprotective mechanisms of Tanshinone IIA (TSA) on mouse cerebral ischemia in vivo.MethodsMale mice were divided into four groups 〔sham-operated, ischemic and treated groups (lower dose and higher dose)〕. The mice were subjected for ischemia-reperfusion three times on bilateral common carotid arteries by knots to establish models of vascular dementia. After ischemia-reperfusion impairment, TSA (4 mg/kg.d, 8 mg/kg.d) was administered by i.p. for 20 days in treated group. 1. We used morris water maze to investigate the learning and memory； 2. Levels of malondialdehyde (MDA), activity of superoxide dismetase (SOD) and glutathione peroxidase (GPX) in brain tissue were detected by spectrophotometer; 3. 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.Results①TSA can improve learning and memory deficits in vascular dementia; ②An elevation of SOD and GPX activity and decrease of MDA level were shown in TSA treated group after brain ischemia; ③Decreased glutamate and gamma-aminobutyric acid induced by chronic brain ischemia were markedly inhibited by TSA pretreatment. ConclusionThe 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.