Pinacidil reduces neuronal apoptosis following cerebral ischemia-reperfusion in rats through both mitochondrial and death-receptor signal pathways

被引：24

作者：

Zhang H. ^{[1
]}

Song L.-C. ^{[1
]}

Liu Y.-Y. ^{[2
]}

Ma Y. ^{[1
]}

Lu Y.-L. ^{[3
]}

机构：

[1] Department of Neurology, Affiliated Shengjing Hospital, China Medical University

[2] Department of Neurology, Tianhe Hospital

[3] Department of Anatomy, China Medical University

来源：

Neuroscience Bulletin | 2007年 / 23卷 / 3期

关键词：

Apoptosis; Caspase-3; Caspase-8; Caspase-9; Cerebral ischemia; Death-receptors; Glipizide; Mitochondria; Pinacidil; Signal pathway;

D O I：

10.1007/s12264-007-0021-2

中图分类号：

学科分类号：

摘要：

Objective: To investigate effect of pinacidil, an ATP sensitive potassium channel (KATP) opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rats. Methods: One hundred male Wistar rats were randomly divided into four groups: A, sham-operated group; B, ischemia-reperfusion group; C, KATP opener treatment group; and D, KATP opener and blocker treatment group. The middle cerebral artery occlusion (MCAO) model was established by using the intraluminal suture occlusion method, neuronal apoptosis was determined by TUNEL staining, and expressions of caspase-8, caspase-9 and caspase-3 mRNA were detected by in situ hybridization. Results: (1) The numbers of apoptotic neurons at 12 h, 24 h, 48 h, and 72 h were significantly less in group C than in groups B and D (P < 0.01 or P < 0.05); and there was no difference between groups B and D at all time points (P > 0.05). (2) The expressions of caspase-3 mRNA and caspase-8 mRNA at all times and the expressions of caspase-9 mRNA at 12 h, 24 h, 48 h, 72 h were significantly lower in group C than in groups B and D (P < 0.01 or P < 0.05); and there were no differences between groups B and D at all time points (P > 0.05). Conclusions: K ATP opener can significantly decrease the neuronal apoptosis and the expressions of caspase-3, caspase-8 and caspase-9 mRNAs following cerebral ischemia-reperfusion. The neuronal apoptosis may be decreased by the inhibition of both mitochondrial and death-receptor signal pathways.

引用

页码：145 / 150

页数：5

共 13 条

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