Effects of inhibition of adenosine monophosphate-activated protein kinase on the expressions of cytochrome c and apoptosis inducing factor in the cortex and hippocampal CA1 region after cerebral ischemia-reperfusion in mice

Abstract

Objeelive To investigate the effect of inhibiting adenosine monophosphate-activated protein kinase （AMPK） on the expressions of cytochrome c （CytC） and apoptosis-inducing factor （AIF） after cerebral ischemia-reperfusion in mice.Methods Thirty-six male C57BL/6 mice were randomly divided into three groups： A sham operation group, an ischemia-reperfusion group, and a compound C group （n = 12 in each group）. Six mice in each group were used for CytC and AIF immunohistochemical detection. A model of middle cerebral artery occlusion （MCAO） was induced by the intraluminal suture method. Compound C was injected intraperitoneaUy in the treatment group when the thread was inserted. The same volume of saline was injected intraperitoneally at the same time point in the sham operation group and theischemia-reperfusion group. At 24 hours after ischemla-reperfusion, the expression of CytC and AIF was observed by immunohistochemical staining. Results A number of CytC positive cells in cortex were seen in the sham operation group. No CytC positive cells were seen in the CA1 region. The number of CytC positive cells in the cerebral cortex （28.86 ± 9. 65/high power field vs. 58.86 ± 9. 65/high power field; t = 7. 615, P =0. 000） and hippocampal CA1 region （13.33 ± 2. 75/high power field vs. 43.33 ± 3.79/high power field; t = 22. 194, P =0. 000） in the compound C group were reduced significantly compared to those in the ischemia- reperfusion group. No AIF-positive cells were seen in the hippocampal CA1 region in the sham operation group. A number of AIF-positive cells were seen in the hippocampal CA1 region. The number of AIF- positive cells of cerebral cortex （32. 16 ± 2. 35/high power field vs. 46. 70 ± 3. 45/high power field; t = 1Z 066, P =0. 000） and hippocampal CA1 region （13. 17 ±3. 91 /high power field vs. 17.35 ±3. 67/high power field; t -2. 700, P =0. 013） in the compound C group were significantly reduced compared to those in the cortex of the ischemia- reperfusion group. Conclusions Inhl＇bition of the AMPK may down-regulate the expressions of CytC and AIF after cerebral ischemia-reperfusion. Key words: AMP-Activated Protein Kinases; Brain Ischemia; Enzyme Inhitors; Cytochromes c; Apoptosis Inducing Factor; Disease Models, Animal; Mice