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. 2007 May;23(3):145-50.
doi: 10.1007/s12264-007-0021-2.

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

Hong Zhang  1 , Li-Chun Song, Yan-Yan Liu, Ying Ma, Yong-Li Lu
Affiliations

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

Hong Zhang et al. Neurosci Bull. 2007 May.

Abstract
in English, Chinese

Objective: To investigate effect of pinacidil, an ATP sensitive potassium channel (K(ATP)) 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, K(ATP) opener treatment group; and D, K(ATP) 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.

目的: 探讨 ATP 敏感性钾通道开放剂 pinacidil 对大鼠脑缺血再灌注后神经元凋亡的保护作用及信号转导机制。

方法: 100 只 Wistar 雄性大鼠随机分为四组: A 组(假手术组)、 B 组 (缺血组)、 C 组 (KATP 开放剂处理组) 及 D 组 (KATP 开放剂和阻断剂处理组)。 用线栓法制备大鼠大脑中动脉缺血(middle cerebral artery occlusion, MCAO) 模型, 用 DNA 断端末端标记法(terminal-deoxynucleotidytransferase-mediated dUTP-biotin nick end labeling, TUNEL) 检测神经元凋亡, 用原位杂交方法检测 caspase-3、 caspase-8 及 caspase-9 mRNA 的表达。

结果: (1) C 组 12 h、 24 h、 48 h、72 h 时间点的凋亡细胞数较 B 、 D 组显著减少(P<0.05 或 P<0.01); B 组和 D 组之间无显著性差异 (P>0.05)。 (2) C 组 caspase-3 mRNA 和 caspase-8 mRNA 在各时间点及 caspase-9 mRNA 在 12 h、 24 h、 48 h、 72 h 时间点的表达显著少于 B 组和 D 组(P<0.01 或 P<0.05), B 组和 D 组之间无显著性差异(P>0.05)。

结论: KATP 通道开放剂能显著减少大鼠脑缺血再灌注后的细胞凋亡及 caspase-3、 caspase-8 及 caspase-9 mRNA 的表达。 KATP 通道开放剂可能通过抑制线粒体通路和死亡受体通路降低神经元凋亡, 保护缺血再灌注损伤后的脑组织。

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