| Objective We developed a rat intermittent hypoxia model to observe their learning and memory behavior of different groups, and detected the expression of TORC1 、 phosphoCREB and BDNF in hippocampus to discuss the effect of edaravone on cognition disorders of intermittent hypoxia rats and the possible mechanism. So as to provide a foundation for edaravone in treatment of obstructive sleep apnea/hypopnea syndrome(OSAHS).Methods 120 adult male Wistar rats of favorable memory were screwed by morris water maze, and were randomly divided into control group(NC group), intermittent hypoxia group(IH group) and edaravone group(ED group), besides, the ED group was further divided into 5 different subgroups by different times of 3d、7d、14d、21d and28 d, and every subgroup contained eight rats. IH group and ED group within hypoxiaed cabin manufacturing hypoxia model simulating intermittent hypoxia environment,IH group and ED group cyclic alternating give different nitrogen and compressed air flow rate per cycle 120 s, IH group and ED group box prompted the minimum oxygen concentration to 5%, and then reply to 21%. NC group in the hypoxia box continuous injection of air,monitoring of oxygen concentration was maintained at 21%.After the rats developed into intermittent hypoxia models, we detected the learning and memory behavior of different groups by morris water maze, besides, of TORC1、phospho-CREB and BDNF protein in hippocampus.Results 1 Effects of intermittent hypoxia on cognitive function of rats: comparison of different timing in the same group: escape latency of the IH group and ED group,gradually prolonged from 14 d along with prolong of the time exposed to hypoxia, and the time across the target quadrant was shortened. While the differences among14d、21d and28 d of IH group was statically significant(P<0.05). The escape latency of 28 d in ED group was longer than the rats of 14 d and 21 d, and the time across the target quadrant was shortened significantly(P<0.05), the differences among14 d and 21 d had no significance(P>0.05). Comparison of different groups in the same timing: compared with NC group, escape latency of 14d、21d and 28 d in IH group and ED group was prolonged,and the time across the target quadrant was shortened significantly(P<0.05), while escape latency of ED group was shortened and time across the target quadrant was prolonged than IH group(P<0.05); 2 The result of immunohistochemistry and western blot of rat hippocampus: comparison of different timing in the same group: expression of TORC1 protein and value of IOD had no significance among different times in NC group(P>0.05); while the result of IH group was enhanced from 3d and then became lower,that was, reached its peak at 7d, and then decreased along with the time exposed to hypoxia, and difference among 3d、7d、14d、21d and 28 d had significance(P<0.05).The expression of TORC1 protein in ED group of 21 d and 28 d was increased than 3d、7d and 14d(P<0.05), while the expression in 3d、7d and 14 d had no significance(P>0.05).Comparison of different groups in the same timing: compared with NC group, expression of TORC1 protein and value of IOD in 3d、7d、14d、21d and 28 d of IH group and ED group were significantly higher(P<0.05); and compared with IH group, the expression of TORC1 protein in ED group, was higher in 3d、21d and 28d(P<0.05), and was lower in7 d and 14d(P<0.05); 3 The result of immunohistochemistry and western blot of rat hippocampus: comparison of different timing in the same group: expression of phosphoCREB protein and value of IOD had no significance among different times in NC group(P>0.05); while the result of IH group was enhanced from 3d and then became lower,that was, reached its peak at 14 d, and then decreased along with the time exposed to hypoxia, and difference among 3d、7d、14d、21d and 28 d had significance(P<0.05).The expression of phospho-CREB protein in ED group of 28 d was increased than 3d 、7d 、 14 d and 21d(P<0.05), while the expression in 3d 、 7d 、 14 d and 21 d had no significance(P>0.05). Comparison of different groups in the same timing: compared with NC group, expression of phospho-CREB protein and value of IOD in 3d、7d、14d、21d and 28 d of IH group and ED group were significantly higher(P<0.05); and compared with IH group, the expression of phospho-CREB protein in ED group, was higher in 3d and 28d(P<0.05), and was lower in 7d 、 14 d and 21d(P<0.05); 4 The result of immunohistochemistry and western blot of rat hippocampus: comparison of different timing in the same group: expression of BDNF protein and value of IOD had no significance among different times in NC group(P>0.05); while the result of IH group was enhanced from 3d and then became lower, that was, reached its peak at 14 d, and then decreased along with the time exposed to hypoxia, and difference among 3d、7d、14d、21d and 28 d had significance(P<0.05). The expression of BDNF protein in ED group of28 d was increased than 3d 、 7d 、 14 d and 21d(P<0.05), while the expression in 3d 、7d 、 14 d and 21 d had no significance(P>0.05). Comparison of different groups in the same timing: compared with NC group, expression of BDNF protein and value of IOD in3 d 、 7d 、 14 d 、 21 d and 28 d of IH group and ED group were significantly higher(P<0.05); and compared with IH group, the expression of BDNF protein in ED group,was higher in 3d and 28d(P<0.05), and was lower in 7d、14d and 21d(P<0.05).Conclusion Intermittent hypoxia could result in learning and memory dysfunction of rats. TORC1、phospho-CREB and BDNF could be induced expression at the early time of intermittent hypoxia, and reach its peak temporarily, but decreased soon, the lasting time was short, so TORC1 might participate in the active of phospho-CREB/BDNF pathway just at the time of 7d intermittent hypoxia.While,our result showed that edaravone could up-regulated, and prolong the express time of TORC1、phospho-CREB and BDNF, and improve the learning and memory function, as a result, could protect brain tissue exposed to intermittent hypoxia. Our research showed that, TORC1/CREB/BDNF signal pathway participated in the protection of edaravone on brain tissue, and this research could provide foundation for the clinical use of edaravone. |
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