Protective effects of inhibition of adenosine monophosphate activated protein kinase activity against cerebral ischemia-reperfusion injury in mice

Objective To observe the effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on shape，function and inflammatory factor of microglia for mice after cerebral ischemia-reperfusion injury and the action mechanism of AMPK inhibition on neuroprotective effects. Methods One hundred and twenty male Kunming mice were randomly divided into sham group，ischemia-reperfusion group，ischemia-reperfusion therapy group (all n=40).Each mouse in ischemia-reperfusion therapy group was given an intraperitoneal inject of compound C (20 mg/kg) after occlusion.A mode of middle cerebral artery occlusion was made by insertion of a thread through internal carotid artery.After 24 hours of reperfusion，neurological deficit scores，infarct volume and expression of specific marker for microglia of ionized calcium-binding adaptor molecule 1 (Iba1) were investigated，and the expressions of inducible nitric oxide synthase (iNOS)，nicotinamide adenine dinucleotide phosphate oxidase 2 (gp91phox)，tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined. Results After cerebral ischemia-reperfusion injury，neurological deficit scores and infarct volume of ischemia-reperfusion therapy group were significantly reduced compared with ischemia-reperfusion group.Small amount of Iba1 ((5.97±1.26) /HP)，iNOS ((6.25±2.02) /HP)，gp91phoxmRNA (0.010±0.007)，TNF-α ((249.62±48.37) pg/mg) and IL-1β ((107.41±11.77) pg/ mg) expressions were observed in sham group.The expressions of Iba1，iNOS，gp91phoxmRNA，TNF-αand IL-1βin ischemia-reperfusion group increased significantly to (11.36±1.18) /HP (P=0.000)，(16.38±2.43) /HP (P=0.000)，0.240±0.067 (P=0.000)，(442.92±97.59) pg/mg (P=0.002) and (209.09±24.69) pg/mg (P=0.000) respectively.Compared with ischemia-reperfusion group，the expressions of Iba1，iNOS，TNF-α and IL-1βin ischemia-reperfusion therapy group decreased significantly to (7.60±1.62) /HP (P=0.000)，(9.32±2.20) /HP (P=0.000)，(290.60±61.40) pg/mg (P=0.007) and (142.61±20.60) pg/mg (P=0.000) respectively，and the expression of gp91phoxmRNA declined to 0.170±0.055 (P=0.052) without statistical significance. Conclusions Inhibition of AMPK activity has neuroprotective effects.Its mechanism may be related to the inhibition of microglia activation and reduction of expression of iNOS，gp91phox，TNF-αand IL-1β. Key words: Brain ischemia; Reperfusion injury; AMP-activated protein kinases; Microglia; Nitric oxide synthase; Tumor necrosis factor-alpha