Pinacidil reduces neuronal apoptosis following cerebral ischemia-reperfusion in rats through both mitochondrial and death-receptor signal pathways.
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.
Zhang
Hong
H
Department of Neurology, the Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, China.
Song
Li-Chun
LC
Liu
Yan-Yan
YY
Ma
Ying
Y
Lu
Yong-Li
YL
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy*; D020169:Caspases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000187:drug effects*; D020110:Pinacidil / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy; D013997:Time Factors
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D020110:Pinacidil; D020169:Caspases