Telmisartan Protection Effect On Oxidative Stress In Mice Hippocampal CA1 By Chronic Intermittent Hypoxia

Objective: To establish simulation with sleep apnea syndrome (Obstructive sleep apnea hypopnea syndrome OSAHS) characteristics of animal models of chronic intermittent hypoxia(CIH), chronic intermittent hypoxia on oxidative stress of mouse hippocampal CA1 injury and for telmisartan on oxidative stress injury.Methods: 32 healthy male C57B6J mice were randomly divided into the CIH group, CIH+ telmisartan group, the air control group and blank control group, test for 12 weeks. spatial learning and memory test by Morris water maze, and detected mice hippocampus area CA1 p47 NADPH oxidase subunit (p47PHOX), 8 - hydroxy-guanosine (8-OHG) by immunohistochemistry.Results: (1) Morris water maze: spatial learning ability: the group of hypoxia decreased learning ability in space, after intervention by the ARB can improve the ability of hypoxia-induced spatial learning decline in escape latency between the different experimental groups there are differences ( F = 3.04, P = 0.045), 22 found that CIH group compared with the control group (P = 0.039), air group (P = 0.013), ARB group (P = 0.048) differences were statistically significant, while the ARB group and control group (P = 0.155), air group (P = 0.064) difference was not statistically significant; spatial memory: CIH group with a blank space and memory, air and ARB were not significant difference. The number of times through the target area CIH group (median = 1 interquartile range=1.5) and the control group (median = 3 Quartile=2), the air group (median = 2 interquartile range =1.75), ARB group (median = 2.5 interquartile range =3.75) between the two groups was not statistically difference (P = 0.136). (2) p47PHOX immunohistochemistry: p47PHOXoptical density of immunohistochemical analysis showed that the cytoplasm in the hippocampal CA1 area in expression,while hippocampal CA1 areap47PHOXCIH group was significantly increased in hippocampal CA1 area by the ARB intervention p47PHOX expression was decline.CIH group (median = 0.1463 interquartile range =0.1389) and the control group (median = 0.0067 interquartile range =0.0168) (P = 0.01) air group (median = 0.0062 interquartile range =0.0281) (P = 0.005) ARB group (median = 0.0031 interquartile range =0.0268) (P = 0.005) differences were statistically significant, ARB group (median = 0.0031 Quartile=0.0268) and the control group (median = 0.0067 interquartile range =0.0168) (P = 0.645) air group (median = 0.0062 interquartile range =0.0281) (P = 0.442) no statistical difference school differences. (3) 8-OHG immunohistochemistry :8-OHG optical density of immunohistochemical analysis showed that the cytoplasm in the hippocampal CA1 area in expression, while CIH hippocampal CA1 area was significantly increased 8-OHG, intervention by the ARB hippocampal District 8-OHG CA1 expression was decreased. CIH group (0.16±0.018) and, ARB group (0.04±0.011) (P = 0.000) difference was statistically significant, ARB group (0.04±0.011) and the control group (0.05±0.015) (P = 0.479), air group (0.03±0.011) (P = 0.750) difference was not statistically significant. Conclusions: (1) chronic intermittent hypoxia can cause NADPH oxidasep47PHOX and 8-OHG expression increased in mice brain, decreased learning ability, suggesting that CIH can cause hippocampal CA1 area oxidative stress damage, eventually leading to cognitive dysfunction.(2) after the intervention of telmisartan on the CIH mice was significantly reduced expression of NADPH oxidase p47phox and 8-OHG, and improve the hippocampus dependent learning. ARB can reduce chronic intermittent hypoxia-induced neuronal oxidative stress injury in mice, and reduce functional damage.