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AIM: To investigate the effects of propofol on the expression of tissue-type plasminogen activator (tPA) and matrix metalloproteinase 9 (MMP9) in the hippocampus and the cognitive function in neonatal rats.METHODS: The 7-day-old rats were randomly divided into 3 groups: the rats in control (CON) group were intraperitoneally injected with normal saline for 7 d;the rats in single dose of propofol anesthesia (SP) group were intraperitoneally injected with normal saline for 6 d and with propofol on the 7th day;the rats in repeated dose of propofol anesthesia (RP) group were intraperitoneally injected with propofol for 7 d.Blood glucose and blood gas analysis were tested in 6 rats of each group.The rats were randomly selected from each group to isolate the hippocampal tissues at 2 h, 24 h, 48 h, 72 h and 30 d after the last injection.The spatial learning and memory functions of the other rats aged 25 d were determined by Morris water maze.The morphological changes of the hippocampus were observed by HE staining and Nissl's staining.The expression of tPA and MMP9 at mRNA and protein levels was determined by RT-PCR and Western blot.RESULTS: Compared with group CON, the protein expression of tPA and MMP9 in RP group was significantly decreased at each time point, while no significant decrease was observed in SP group except at the time point of 24 h.Compared with CON group, the mRNA expression of tPA and MMP9 was down-regulated obviously in RP group, which was not significantly down-regulated in SP group.From the 3rd training day of Morris water maze beginning, the escape latency was prolonged, and the space exploration time and the number of crossing the original platform location were reduced in RP group compared with CON group and SP group, while no significant difference was observed between CON group and SP group.Compared with CON group, the number of nerve cells reduced and nerve cells arranged in disorder in the hippocampus in RP group.Moreover, the number of Nissl body decreased significantly and finally developed into neuronal degeneration and necrosis in RP group, and no significant difference between SP group and CON group was observed.CONCLUSION: Repeated dose of propofol anesthesia leads to long-term cognitive dysfunction in neonatal rats, which may be related to the down-regulation of tPA and MMP9 expression and destruction of normal morphology and function of neurons in hippocampus, whereas single dose of propofol anesthesia has no such effects.
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Aim To investigate the role of matrix metalloproteinase-9 down-regulation in the learning and memory dysfunction induced by propofol treatment in rats.Methods 7-day-old SD rats were randomly divided into three groups(n=18):control group(NS group) and repeated doses of propofol group(RP group) was intraperitoneally injected with normal saline and propofol respectively for consecutive seven days, single dose of propofol group(SP group) were intraperitoneally injected with normal saline first for consecutive six days, and then injected with propofol on 7th day.The blood gas and glucose levels were monitored of six rats randomly selected from each group.Morris water maze was conducted to test the learning and memory functions of the remaining rats.The expression of MMP-9, BDNF and caspase-3 was detected by Western blot, and the hippocampal neuron apoptosis was determinated by TUNEL staining.Results Compared with NS group and SP group, the escape latency in RP group was prolonged significantly, exploration time and the number of crossing the platform in RP group were markedly decreased(P0.05).Conclusions Repeated exposure to propofol can lead to a decline in long-term learning and memory functions in neonatal rats, which may be related to the down-regulation of MMP-9 expression, proBDNF and mBDNF conversion disorder in hippocampus and the apoptosis of hippocampal neurons.However, single exposure to propofol has no significant effect.
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Aim To observe the improvement effects of parecoxib on ventricular remodeling after acute myocardial infarction in rats and its influence on PI3K/Akt signaling pathway.Methods Forty male Sprague-Dawley rats were randomly divided into five groups(n=8):sham operation group (group S), ventricular remodeling model group(group R), low dose of parecoxib group(group P1), middle dose of parecoxib group(group P2), and high dose of parecoxib group(group P3).A myocardial infarction model was established by ligating the left anterior descending branch(LAD) of coronary artery in group R, group P1, group P2 and group P3.One day after the operation,the rats were given intraperitoneal injection of 4,8,12 mg·kg-1 parecoxibin Group P1, group P2 and group P3,respectively, for two weeks.The same volume saline was given in group S and group R.Four weeks later, LVSP, LVEDP,+dp/dtmax,-dp/dtmax were monitored.The hearts were harvested to calculate left ventricular hypertrophy index.The pathological change of heart was examined with an optical microscope.The expressions of atrial natriuretic peptide(ANP) mRNA and brain natriuretic peptide(BNP) mRNA were detected by RT-PCR.The expression of PI3K,Akt,P-Akt and caspase-3 was detected by Western blot.Results Compared with group S, the cardiac function was decreased, the left ventricular hypertrophy index, the expression levels of ANP,BNP mRNA, caspase-3 were increased, and the expression levels of PI3K, P-Akt were reduced in group R(all P<0.05).Compared with group R, the cardiac function was ameliorated, the left ventricular hypertrophy index were reduced in group P2 and group P3(all P<0.05).The expression levels of ANP,BNP mRNA, Caspase-3 were decreased, and the expression levels of PI3K and P-Akt were increased in group P1,group P2 and group P3(all P<0.05).Conclusions Middle and high doses of parecoxib can mitigate the process of ventricular remodeling after myocardial infarctionand improve the myocardial function, and its underlying mechanism may be related to activating PI3K/Akt signaling pathway.