The Effection Of Edaravone On Expression Of JNK/P38 And Apoptosis Of Neurons In Hippocampus Of Hypoxic Rats

Objective To dynamic observe the expression of JNK/ P38 and neuronal apoptosis in rats’ hippocampus,to investigate them intervention of Edaravoneon by establishing a model of intermittent hypoxic rats,which may be expected to improve dysfunction of nervous system caused by obstructive sleep apnea hypopnea syndrome.Methods Randomly allocated 120 adult male wistar rats weighting in(180±5) g into the Unhandled group(UC group),Intermittent hypoxic group(IH group),Edaravone intervention group(ED group).Each group was divided into 3d, 7d, 14 d, 21 d, 28 d sub groups,and each subgroup with 8 rats.Intermittent hypoxia group and Edaravone intervention group within hypoxiaed cabin manufacturing hypoxia model simulating intermittent hypoxia environment,UC group in the hypoxia box continuous injection of air 120 s, monitoring of oxygen concentration was maintained at 21%.The end of the experiment in normal feeding box given food and water enough, each group of the living environment and feeding conditions are same.At the end of each experimental observation time points the rats brains were randomly removed, the expression of JNK and P38 in hippocampus were investigated by immunohistochemistry, real-time PCR,and the apoptosis of neurons was detected by the TUNEL method.Results 1 The expression of JNK, P38 protein in rats’ hippocampus in each group by immunohistochemistry:the content of JNK,P38 protein are rare in the UC group,compared with UC group,the IH group and ED group IOD value of JNK,P38 protein expression in rats’ hippocampus are higher(P<0.05);but compared with.IH group,the ED group IOD value of JNK, P38 protein expression in rats’ hippocampus are lower(P<0.05).Compared between subgroups in UC group,the IOD value of JNK, P38 protein expression in rats’ hippocampus has no significant difference(P>0.05), while compared IH group,ED group,between the two each subgroups were all significantly statistic,in addition the IOD value of JNK,P38 protein expression in rats’ hippocampus prolonging was increased gradually,and reached its peak at 28d(P<0.05);2 The level of JNK,P38 m RNA in rats’ hippocampus of each group were detected by RT-PCR : the content of JNK,P38 m RNA are small in the UC group,compared with UC group,the IH group and ED group JNK, P38 m RNA expression in rats’ hippocampus are higher(P<0.05);but compared with IH group,the JNK,P38 m RNA expression in the ED group rats’hippocampus are lower(P<0.05).Compared between subgroups in UC group,the JNK,P38 m RNA expression in rats’ hippocampus has no significant difference(P>0.05),while compared IH group,ED group,between the two each subgroups were all significant ly statistic,in addition,JNK,P38 m RNA expression in rats’ hippocampus prolonging was increased gradually,and reached its peak at 28d(P<0.05);3 The morphology of apoptotic cells were round or oval observed by optical microscope.Compared with UC group,IH group,ED group cell apoptosis index in hippocampus area was increased,compared with the IH group,cell apoptosis index in ED group is lower(P<0.05).Compared between subgroups in UC group,the cell apoptosis index in rats’ hippocampus has no significant difference(P>0.05),while compared IH group,ED group,between the two each subgroups were all significantly statistic(P<0.05),in addition cell apoptosis index in rats’ hippocampus prolonging was increased gradually,and reached its peak at 28d(P<0.05);4The expression of JNK,P38 protein and the level of JNK,P38 m RNA in IH group,ED group were significant positively correlated with apoptosis index.Conclusion 1 The JNK/ P38 protein expression and the level of JNK/P38 m RNA in hippocampal neurons of intermittent hypoxia rats were increased gradually with the time prolonged,which means JNK/P38 signal pathway may be involved in neuronal damage caused by chronic intermittent hypoxia, further correlation analysis also confirmed this point;2 The JNK/ P38 protein expression and the level of JNK/P38 m RNA in hippocampal neurons of edaravone group were lower than IH group, neuronal apoptosis were also reduced significantly;3 The protective effect of edaravone on brain injury in a rat model of intermittent hypoxia,may be related to the inhibition of p-P38,pJNK expresstion and mediated neuronal apoptosis by them.