ABSTRACT
Objective To investigate whether Wnt/β-catenin signaling pathway mediating the neuroprotection of isoflurane post-conditioning in hippocampal neurons damage induced by ischemia/reperfusion injury in rats.Methods According to the randomized principle, 60 male Sprague-Dawley rats were randomly divided into five groups (12 rats in each group):sham group (group S), model group (group M), ISO+model group (group MI), ISO+model+DKK-1 group (group MDI) and model+DKK-1 group (group MD).A rat model of middle cerebral artery occlusion (MCAO) was established with 90 min ischemia followed by 24 hreperfusion.Group S was only exposed to one side of the internal carotid artery without fishing line.Isoflurane post-conditioning groups (group MI, MDI) were immediately treated with 1.5％isoflurane for 60 min at the onset of reperfusion.DKK-1 (5μg/kg) was injected intracerebroventricularly 30 min before the model established in group MDI and group MD.After reperfusion for 24 h, Longa score method was used for neurological deficit score.HE staining and Tunel fluorescence was employed to observe the morphological changes of neurons.Immunohistochemistry and Western Blot were applied to detect the expression of target protein in CA1 region.Results Compared with group S, the neurobehavioral score, the number of apoptosis and the expression of Bax and GSK-3βprotein in group M all increased (P<0.05), while the expression ofβ-catenin and Bcl-2/Bax ratio decreased (P<0.05) ;Compared with group M, the neurobehavioral score, the number of apoptosis and the expression of Bax protein were significantly decreased (P<0.05), while the expression of Bcl-2, β-catenin protein and the Bcl-2/Bax ratio were significantly increased (P<0.05) in group MI.Compared with group MI, the neurobehavioral score, the number of apoptosis, Bax and GSK-3βprotein in group MDI were significantly increased (P<0.05), while the Bcl-2, β-catenin protein expression, and Bcl-2/Bax ratio were significantly decreased (P<0.05).Conclusion Isoflurane post-conditioning may protect the hippocampus neurons against cerebral ischemic reperfusion-induced damage via the way that the Wnt/β-catenin signaling pathway regulates the expression levels of Bcl-2 and Bax proteins in rats.
ABSTRACT
Objective To evaluate the effect of dezocine on cognitive function after sevoflurane anesthesia in a rat model of physiological stress.Methods Physiological stress was induced by applying repeated foot shock stimulation and confirmed by open field test.Thirty Spragne-Dawley rats with physiological stress,weighing 180-220 g,were divided into 3 groups (n=10 each) using a random number table:control group (group C),sevoflurane group (group S) and dezocine plus sevoflurane group (group D+S).Normal saline 0.5 ml was intraperitoneally injected at 6 h of oxygen inhalation in group C.Normal saline 0.5 ml was intraperitoneally injected at 6 h of 3.0％ sevoflurane inhalation in group S.Dezocine 3 mg/kg was intraperitoneally injected at 6 h of 3.0％ sevoflurane inhalation in group D+S.At 1,12,24 and 48 h after the end of intraperitoneal injection (T1-4),Morris water maze test was performed,and the time of staying at the original platform quadrant and frequency of crossing the original platform were recorded.The rats were sacrificed after the end of Morris water maze test,brains were removed and hippocampi were isolated for determination of nitric oxide synthase-1 (nNOS) expression (by Western blot) and nNOS positive cells (by immunohistochemistry).Results Compared with group C,the time of staying at the original platform quadrant was significantly shortened at T1,2,the frequency of crossing the original platform was reduced at T1,the expression of nNOS in hippocampus was down-regulated,and the number of nNOS positive cells in hippocampal CA1 region was reduced in group S (P＜0.05),and no significant change was found in the parameters mentioned above in group D+S (P＞0.05).Compared with group S,the time of staying at the original platform quadrant was significantly prolonged at T1,the frequency of crossing the original platform was increased at T1,2,the expression of nNOS in hippocampus was up-regulated,and the number of nNOS positive cells in hippocampal CA1 region was increased in group D+S (P＜0.05).Conclusion Dezocine can improve cognitive function after sevoflurane anesthesia in a rat model of physiological stress,and the mechanism may be related to up-regulating nNOS expression in hippocampi.