RESUMO
Objective To evaluate the effect of monosialoganglioside (GM-1) on hippocampal protein kinase B (Akt) /glycogen synthase kinase 3β (GSK-3β) signaling pathway in the rats undergoing cardiopulmonary bypass (CPB).Methods Eighteen healthy male Sprague-Dawley rats, aged 6 months, weighing 400-500 g, were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C), CPB group and GM-1 group.GM-1 20 mg/kg was added to the priming solution in group GM-1, while the equal volume of normal saline was given in group CPB.At 3 h after termination of CPB, blood samples were taken from the jugular vein for determination of plasma neuron-specific enolase (NSE) and S-100β protein concentrations using enzyme-linked immunosorbent assay.After blood sampling, the rats were sacrificed, and the hippocampi were isolated for microscopic examination of the ultrastructure of the hippocampal neurons (with electron microscope), and for detection of neuronal apoptosis (with light microscope) and phosphorylation of Akt and GSK-3β (by Western blot).Results Compared with group C, the concentrations of plasma NSE and S-100β protein, and the number of apoptotic neurons were significantly increased in CPB and GM-1 groups, the phosphorylation of Akt and GSK-3β was decreased in group CPB, and the phosphorylation of Akt and GSK-3β was increased in group GM-1 (P＜0.05).Compared with group CPB, the concentrations of plasma NSE and S-100β protein, and the number of apoptotic neurons were significantly decreased, the phosphorylation of Akt and GSK-3β was increased (P＜0.05), and the pathological changes were reduced in group GM-1.Conclusion GM-1 can reduce apoptosis in hippocampal neurons through activating Akt/GSK-3β signaling pathway, thus mitigating CPB-induced brain injury in rats.
RESUMO
Objective To investigate the effect of monosialoganglioside GM-1 on cardiopulmonary bypass (CPB)-induced brain injury in rats.Methods Twenty-seven adult male Sprague-Dawley rats,weighing 350-450 g,aged 15 months,were randomly divided into 3 groups (n=9 each): control group (C group),CPB group and GM-1 group.The animals were anesthetized with chloral hydrate,tracheostomized and mechanically ventilated.Right common carotid and right jugular vein were cannulated for closed-chest CPB.In groups CPB and GM-1,the rats underwent 1 h CPB.GM-1 20 mg/kg was added to the priming solution in group GM-1,while the equal volume of normal saline was given in group CPB.The animals were sacrificed at 3 h after termination of CPB or 3 h after the end of ventilation in group C,the brains were removed and the hippocampi isolated for microscopic examination and for determination of apoptosis (using TUNEL) and Bax and Bcl-2 protein expression (by immunohistochemistry and Western blot).Results Compared with group C,the number of apoptotic neurons and ratio of Bax/Bcl-2 were significantly increased,and the expression of Bcl-2 and Bax protein was up-regulated in groups CPB and GM-1 (P ＜ 0.05).Compared with group CPB,the number of apoptotic neurons and ratio of Bax/Bcl-2 were significantly decreased,the expression of Bax protein was down-regulated and the expression of Bcl-2 protein was up-regulated in group GM-1.The pathological changes were severe in group CPB and attenuated in group GM-1.Conclusion GM-1 can attenuate CPB-induced brain injury in rats and inhibition of the apoptosis in neurons may be involved in the mechanism.