| Objective: To observe the influence of ERK1/2 signal pathway inhibitor SL327 on the changes of cognitive function and the expression of PSD-95 and p-ERK1/2 in hippocampus of OSAS model rats and to explore its possible mechanism.Methods: 50 healthy male SD rats were randomly divided into normal control group,intermittent hypoxia 7d,14 d,21d,28 d group,SL327 pretreatment group(CIH28d),solvent control group(CIH28d).Chronic intermittent hypoxia was adopted to mimic obstructive sleep apnea syndrome(OSAS)in rats.The expression of p-ERK1 / 2 and PSD-95 in hippocampus of rats with intermittent hypoxia 7d,14 d,21d and 28 d was examined by Western blotting.Compared with the CIH group,the effect of SL327 on the expression of p-ERK1/2 and PSD-95 in hippocampus of OSAS model rats was observed by pretreating the experimental rats with SL327 during peak time of p-ERK1/2 expression.Morris water maze,HE staining were used to observe and analyze the changes of ethology,histopathological,and detect the location of the target protein respectively.Results:1.The results of oxygen saturation monitoring analysis showed that the oxygen saturation was(67.49 ± 3.69)% in the hypoxia interval and significantly lower than that in the reoxygenation interval(96.15 ± 1.81)%(P <0.05),and the rats lifted heads up to breathe and the abdominal breathing was deepened during the hypoxia interval,which conformed to the OSAS model criteria.2.Morris water maze test:Compared with the normal control group,the escape latency and the number of crossings of the target area of CIH 7d group did not change significantly,while the escape latency was significantly prolonged at the time of CIH 14 d,CIH 21 d and CIH 28d(P <0.05),and it was positively correlated with intermittent hypoxia(P <0.05),at the same time,the number of crossings of the target area was significantly decreased(P<0.05),and it was negative correlated with intermittent hypoxia(P <0.05).The escape latency was significantly decreased in the SL327 intervention group(CIH 28d),while the number of crossings of the target area was significantly higher than CIH group in the same period(P<0.05).3.HE staining results: The neurons in the hippocampus of the normal control group were dense and arranged in the normal control group.In the hippocampus of CIH 28 d group,the neurons of the hippocampus were narrowed,the structure was irregular,the cytoplasm was stained strongly,the nucleus was enlarged and the cell gap was enlarged.In the SL327 group,the neuronal degeneration and necrosis of the hippocampus could be observed,the cytoplasm was stained slightly,and the degree is lighter than CIH 28 d group.4.Western blotting results show : The expression of p-ERK1 / 2 was detected in the hippocampus of each group.Compared with the normal control group,the expression of CIH 7d,CIH 14 d,CIH 21 d and CIH 28 d were up-regulated(P <0.05),and it was positively correlated with intermittent hypoxia(P <0.05).Compared with CIH 28 d,the SL327 intervention group(CIH 28d)was significantly lower than that of CIH group(P<0.05).The expression of PSD-95 was detected in the hippocampus of the rats in each group.Compared with the normal control group,the expression of CIH 14 d,CIH 21 d and CIH 28 d decreased(P <0.05),and it was positively correlated with intermittent hypoxia(P<0.05),but there was no significant change in CIH 7d group,the SL327 intervention group(CIH 28d)was significantly higher than CIH group in the same period(P <0.05).5.Immunohistochemical results shown : The positive staining of p-ERK1 / 2 cells in hippocampus of rats was brown or yellow,mainly expressed in the nucleus and cytoplasm of neurons.PSD-95 positive staining cells were brown,mainly expressed in the neuronal membrane.Conclusion: Cognitive impairment in OSAS rats may be related to the increased expression of p-ERK1/2 and the decreased expression of PSD-95.Inhibition of the ERK1/2 signal pathway can significantly reduce the expression of p-ERK1/2 and increase the expression of PSD-95,thereby improving the cognitive function of OSAS rats. |
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