Effects of ATP sensitive potassium channel opener on the mRNA and protein expressions of caspase-12 after cerebral ischemia-reperfusion in rats.
OBJECTIVE
To investigate effects of K(ATP) opener on the expressions of caspase-12 mRNA and protein, and to explore the role of endoplasmic reticulum (ER) stress pathway in the mechanism of K(ATP) opener protecting against neuronal apoptosis after cerebral ischemia-reperfusion.


METHODS
Two hundred rats were randomly divided into four groups: sham operation group, ischemia-reperfusion group, K(ATP) opener group, and K(ATP) blocker group. The middle cerebral artery occlusion (MCAO) model was established by intraluminal suture occlusion method; neuronal apoptosis was detected by TUNEL staining. The mRNA and protein expressions of caspase-12 were detected by semi-quantitative RT-PCR and immunohistochemical staining, respectively.


RESULTS
In ischemia-reperfusion group, K(ATP) opener group and K(ATP) blocker group, the number of apoptotic cells and the mRNA and protein expressions of caspase-12 gradually increased following cerebral reperfusion, and reached the peak at 24 h. In K(ATP) opener group, the number of apoptotic cells was significantly less than that in ischemia-reperfusion group and K(ATP) blocker group at 12 h, 24 h, 48 h and 72 h (P< 0.05 or P< 0.01); while the mRNA and protein levels of caspase-12 were significantly less than those in ischemia-reperfusion group and K(ATP) blocker group at all times (P< 0.05 or P< 0.01). There were no differences between the ischemia-reperfusion group and K(ATP) blocker group at each time (P> 0.05).


CONCLUSIONS
K(ATP) opener may protect neurons from apoptosis following the cerebral ischemia-reperfusion by inhibiting ER stress pathway.
Zhang
Hong
H
Department of Neurology, the Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, China. zhangh.7211@163.com
Song
Li-Chun
LC
Jia
Chun-Hong
CH
Lu
Yong-Li
YL
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D054086:KATP Channels / Q000819:agonists*; D008297:Male; D020110:Pinacidil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*
D054086:KATP Channels; D012333:RNA, Messenger; D020110:Pinacidil; D053454:Caspase 12