多奈哌齐促进脑梗死后室管膜下区神经发生的实验研究

Donepezil promotes neurogenesis in the subventricular zone : an experimental study of cerebral ischemia in mice

目的:探讨多奈哌齐对脑梗死后室管膜下区神经发生的作用。方法:将60只雄性小鼠随机分为假手术+溶剂组、脑梗死+溶剂组、脑梗死+多奈哌齐组,各20只。建立局灶性大脑中动脉闭塞(MCAO)模型。采用Mash1标记神经干/祖细胞,Doublecortin(DCX)标记神经母细胞。免疫荧光观察各组小鼠室管膜下区DCX的表达,Western blot分析各组小鼠室管膜下区Mash1和DCX表达量的变化。结果 :MCAO术后10 d,各组小鼠室管膜下区均可观察到表达DCX的细胞,且脑梗死+溶剂组DCX和Mash1的表达较假手术+溶剂组明显增多(P<0.05),脑梗死+多奈哌齐组DCX和Mash1的表达较另两组显著增加(P<0.05)。结论:多奈哌齐作为一种胆碱酯酶抑制剂,能够促进脑梗死后室管膜下区神经发生。

Objective To investigate the influence of donepezil on neurogenesis in the subventricular zone（SVZ） under the cerebral ischemic conditions. Methods Sixty mice were randomly assigned to a sham ＋vehicle group, a middle cerebral artery occlusion（MCAO） ＋ vehicle group and a MCAO ＋ donepezil group, 20 in each group. A model of MCAO was established. Neural stem cells / progenitor cells were labeled by Mash1,and neuroblasts were labeled by doublecortin（DCX）. The expressions of DCX in the SVZ cells of each group were detected by immunofluorescence. The expressions of Mash1 and DCX in the SVZ cells of each group were quantified by Western blot. Results 10 days after MCAO was undergone, DCX-positive cells were seen in the SVZ of each group, and the expressions of DCX and Mash1 in MCAO ＋ vehicle group were markedly increased as compared with the sham ＋ vehicle group（P〈0.05）, and that in MCAO ＋ donepezil group were significantly increased as compared with the other two groups（P〈0.05）. Conclusion As a kind of acetylcholinesterase inhibitors, donepezil can promote neurogenesis in SVZ under the cerebral ischemic conditions.