Effects of inhibition of AMP-activated protein kinase on cytochrome c expression in the cortex and hippocampus after focal cerebral ischemia-reperfusion in mice / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effects of of inhibition of AMP-activated protein kinase (AMPK) on cytochrome c (CytC) expression in the cortex and hippocampus after focal cerebral ischemia-reperfusion in mice. Methods Thirty-six male C57BL/6 mice were randomly divided into 3 groups a sham operation group, an ischemia-reperfusion group, and a compound C group (n = 12 in each group). The mice of the compound C group were intraperitonealy injected an AMPK specific inhibitor compound C (20 mg/kg) at the time of ischemia. A model of middle cerebral artery occlusion was induced by a modified suture method. After 24 h of reperfusion, Western blot was used to detect the expression levels of AMPK, phosphorylated-AMPK (p-AMPK), and cytoplasm CytC in the cortex and hippocampus in the ischemic side. Results p-AMPK/MPK levels in the cortex in the sham operation group, ischemia-reperfusion group, and compound C group were 0. 701 ± 0. 197, 1. 408 ± 0. 322, and 0. 930 ± 0. 229, respectively (F = 12. 000, P =0. 001); p-AMPK/MPK levels in the hippocampus were 0. 685 ± 0. 228, 1. 507 ± 0. 418, and 0. 964 ± 0. 378, respectively ( F = 8. 530, P = 0. 003 ); p-AMPK/AMPK levels both in the cortex ( P < 0. 001 ) and hippocampus (P = 0. 001) in the ischemia-reperfusion group were significantly higher than those in the sham operation group, p-AMPK/AMPK levels both in the cortex (P = 0. 005) and hippocampus (P = 0. 017) in the compound C group were significantly lower than those in the ischemia-reperfusion group. CytC levels in the cortex in the sham operation group, ischemia-reperfusion group, and compound C group were 0. 496 ±0. 278, 1. 461 ± 0. 321, and 1. 018 ± 0. 175, respectively (F = 19. 915, P < 0. 001); CytC levels in the hippocampus were 0. 511 ± 0. 257, 1. 610 ± 0. 441, and 0. 921 ± 0. 228 (F = 17. 795, P < 0. 001); CytC levels both in the cortex (P < 0. 001) and hippocampus (P < 0. 001) in the ischemia-reperfusion group were significantly higher than those in the sham operation group, while CytC levels both in the cortex (P = 0. 011) and hippocampus (P = 0. 002) in the compound C group were significantly lower than those in the ischemia-reperfusion group. Conclusion Inhibition of the AMPK may down-regulate the cytoplasm CytC expression in the cortex and hippocampus after cerebral ischemia-reperfusion in mice.