EDT, a tetrahydroacridine derivative inhibits cerebral ischemia and protects rat cortical neurons against glutamate-induced cytotoxicity  

四氢吖啶类衍生物EDT抑制脑缺血及保护大鼠皮层神经元抗谷氨酸诱发的细胞毒性(英文)

作　　者：盛瑞[1] 刘国卿[1] 

机构地区：[1]中国药科大学药理教研室

出　　处：《Acta Pharmacologica Sinica》2003年第5期390-393,477,共5页中国药理学报（英文版）

摘　　要：AIM: To study the effects of 9-(4-ethoxycarbonylyphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydroacridine (EDT) on cerebral ischemia and glutamic acid (Glu) and sodium nitroprusside (SNP)-induced neurocytotoxicity in primary cortical culture. METHODS: Focal cerebral ischemia was produced by permanent occlusion of left middle cerebral artery (MCA) in mice. The infarct tissue was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining technique. The extent of neurological deficits was evaluated. In primary cortical culture, colorimetric MTT assay was used to determine cell survival rate, and leakage of LDH and NO release assay were measured. RESULTS: In focal cerebral ischemia, pretreatment with EDT 2.5, 5, and 10 mg/kg and nimodipine 2 mg/kg for 5 d effectively improved the abnormal neurological symptoms and reduced the infarct rate. In primary cortical culture, EDT 0.01-3μmol/L concentration-dependently attenuated NO release induced by Glu 500 μmol/L and increased the cell survival. It also remarkably reduced the LDH excessive efflux. CONCLUSION: EDT possessed protective effects against cerebral ischemia, which may be related to blocking Glu receptor and inhibiting NO formation.目的:考察9-(4-乙氧羰基苯氧基)-6,7-二甲氧基-1,2,3,4-四氢吖啶盐酸盐(EDT)对大鼠局灶性脑缺血及谷氨酸(Glu)和硝普钠(SNP)致鼠皮层神经元损伤的作用。方法:灼断小鼠一侧大脑中动脉形成局灶性脑缺血模型,用氯化三苯基四氮唑(TTC)染色法测定脑梗塞率同时对神经症状进行评分。在原代培养的大鼠皮层神经细胞,采用MTT比色法,测定培养质内LDH及NO释放量。结果:EDT 2.5、5和10mg/kg及尼莫地平2mg/kg灌胃5d显著改善局灶性脑缺血小鼠的神经运动功能,缩小脑梗塞范围。在原代培养的鼠皮层神经细胞,EDT 0.01-3μmol/L浓度依赖地对抗Glu诱发的NO过量形成,并提高MTT微量比色值,同时,减少SNP引起的LDH过量释放,提高细胞存活率。结论:EDT能有效对抗脑缺血损伤,其神经保护作用可能是通过阻断Glu受体及抑制NO生成而实现的。

关 键 词：9-(4-ethoxycarbonylyphenoxy)-6 7-dimethoxy-1 2 3 4-tetrahydroacridine(EDT) tetrahydroacridines brain ischemia cell culture neurons glutamic acid nitric oxide 

分 类 号：R96[医药卫生—药理学]