Objective To investigate the effect of irisin on Notch signaling pathway in rats with global cerebral ischemia-reperfusion.
Methods A total of 60 healthy adult Sprague-Dawley rats were randomly divided into sham group (group A), global cerebral ischemia reperfusion group (group B), irisin-treated group (group C), DAPT (seletive inhibitor of Notch signaling pathway) treated group (group D) and irisin combined with DAPT-treated group (group E), each group enrolled 12 rats. A rat model of global cerebral ischemia-reperfusion for group B was established by improved clipping of bilateral common carotid artery occlusion for 20 minutes and reperfusion for 24 hours combined with hypotension. In group A, only bilateral common carotid arteries separated without ligation. Thirty minutes before cerebral ischemia, rats in group C were injected with 10 μg/kg irisin intravenously, rats in group D were intraperitoneally injected with DAPT 100 mg/kg, and rats in group E were injected with both irisin intravenously and DAPT intraperitoneally. Normal saline was intravenously injected at the corresponding time points in group A and group B. Twenty-four hours after reperfusion, neurological function was evaluated by neurological deficit score (NDS). The brain water content (BWC) was used to assess brain edema. HE staining and TdT-nediated dUTP nick end labeling (TUNEL) were used to observe the neuronal necrosis and apoptosis of hippocampal CA1 region in rats respectively. The protein expression of Caspase-3, Notch1, NICD, and Hes1 were detected by Western blot.
Results Compared with group A, the NDS were higher, BWC were increased, the morphological damage were worse, the TUNEL positive cells increased, and the protein expression of Caspase-3, NICD, Notch1 and Hes1 up-regulated in other four groups (P < 0.05). Compared with group B, the NDS were lower, the BWC were decreased, the morphological damage alleviated, the TUNEL positive cells reduced, the expression of Caspase-3 down-regulated, the protein expression of NICD, Notch1 and Hes1 up-regulated in group C (P < 0.05). Compared with group C, the NDS were higher, the BWC were increased, the morphological damage were worse, the TUNEL positive cells increased, the expression of Caspase-3 up-regulated, and the protein expression of NICD, Notch1 and Hes1 down-regulated in groups D and E (P < 0.05).
Conclusion Irisin pretreatment can alleviate the morphological damage and cerebral edema after global cerebral ischemia-reperfusion. The mechanism may be related to the early activation of Notch signaling pathway. |
