Abstract
Objective To investigate the neural protection of liraglutide in cerebral ischemia-reperfusion rats. Methods 100 male Sprague Dawley rats were randomly divided into sham group (n=20), ischemia-reperfusion group (n=20), high-dose liraglutide treatment group (n=20), middle-dose liraglutide treatment group (n=20) and low-dose liraglutide treatment group (n=20). The later 4 groups were used to build middle cerebral artery occlusion/reperfusion model.24 hours after the occlusion/reperfusion model was build, all rats were sacrificed and the neurological dysfunction was scored. The cerebral infarction size was measured by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. TdT-mediated dUTP nick end labeling (TUNEL) was applied to observe the neuronal apoptosis. Western blotting was used to analyze the protein expression of B cell lymphoma/leukemia-2 (bcl-2) and B celI lymphoma/leukemia-2 associated X protein (bax). Quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression of microRNA (miRNA, miR)-497. Results The neurological deficit scores, infraction volume, apoptotic cells, expression of bax protein and miRNA-497 in ischemia-reperfusion group were significantly increased compared to sham group(P=0.000). The protein level of bcl-2 in ischemia-reperfusion group was significantly decreased compared to sham group(P=0.000). Liraglutide treatment could significantly improve the neurological deficits resulting from cerebral ischemia-reperfusion(P=0.000), reduce the volume of cerebral infarction (P=0.000) and the number of apoptotic cells(P=0.006), decrease the expression of bax protein(P=0.002) and miRNA-497(P=0.002), and increase the expression of bcl-2 protein (P=0.000). The effect of liraglutide was positively correlated with the dose. Conclusion Liraglutide can improve neurological dysfunction, cerebral infarction and neuronal apoptosis induced by ischemia-reperfusion. The mechanism may be related to the down-regulation of miR-497 expression by liraglutide. Key words: Liraglutide; Cerebral Ischemia-reperfuson; MicroRNA-497
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