Hong ZHANG¹, Li-Chun SONG¹, Chun-Hong JIA¹, Yong-Li LU<sup>2

1</sup> Department of Neurology, the Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, China
² Department of Anatomy, China Medical University, Shenyang 110001, China

Abstract

Objective
To investigate effects of KATP 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 KATP 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, KATP opener group, and KATP 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, KATP opener group and KATP 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 KATP opener group, The number of apoptotic cells was significantly less than that in ischemia-reperfusion group and KATP 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 KATP blocker group at all times (P < 0.05 or P < 0.01). There were no differences between the ischemia-reperfusion group and KATP blocker group at each time (P > 0.05).
Conclusion
KATP opener may protect neurons from apoptosis following the cerebral ischemia-reperfusion by inhibiting ER stress pathway.

Keywords

ATP sensitive potassium channel; cerebral ischemia; apoptosis; endoplasmic reticulum; caspase-12

[SpringerLink]