Study Of The Role Of ERK And P38MAPK Pathway In Cx43 Phosphorylation After Subarachnoid Hemorrhage

Object:To investigate the role of ERK and P38 MAPK pathway in cerebral vasospasm induced by Cx43 phosphorylation after subarachnoid hemorrhage(SAH)in rats,for providing laboratory evidence and clinical guidance for the prevention and treatment of cerebral vasospasm.Methods:In this experiment,ninety healthy adult male Sprague Dawley rats weighing between 300 and 350 g were randomly divided into 5 groups,18 in each group,which were respectively Sham group,SAH group,Vehicle group,SAH+SB203580 group and SAH+PD98059 group.The SAH rat model was established by a modified version of double injecting blood into the prechiasmatic cistern method,and HE staining was used to identify the successfully establishment of this model.The neurobehavioral score of the rats in each group on the 1st,3rd,5th,7th day were graded by the Garcia neurobehavioral scoring method.On the 7th day,the expressions of pCx43,pP38 MAPK,P38MAPK,ERK1/2 and pERK1/2 in the basilar artery of the rats in each group were detected by Western blot.The diameter of the basilar artery in each group of rats in day 7 was measured by Pressure myograph measurement.Results: In terms of model,the SAH rat model was successfully established by secondary blood injection into the prechiasmatic cistern in this study.The most obvious feature was that a large amount of blood was found in the subarachnoid space of the SAH group,and many red blood cells were observed accumulation under the HE staining microscope.In terms of neurobehavioral scores,the scores on the 1st,3rd,5th,and 7th days of the SAH group were significantly lower than those of the Sham group at the same time point.The scores on the 1st,3rd,5th,and 7th days of the SAH+SB203580 group and the SAH+PD98059 group were higher than those of the SAH group at the same time point.In terms of protein expression,the expression of pCx43 in the SAH group was higher than that in the Sham group.The SAH+SB203580 group and the SAH+PD98059 group showed a decrease in pCx43 expression compared to the SAH group.The expression of pP38 MAPK was higher than that in the Sham group.The expression of pP38 MAPK was decreased in the SAH+SB203580 group and the SAH+PD98059 group compared with the SAH group.The expression of pERK1/2 was higher than that in the Sham group.The expression of pERK1/2 was decreased in the SAH+SB203580 group and the SAH+PD98059 group compared with the SAH group.In terms of basilar artery diameter,the diameter of basilar artery in SAH group was smaller than that in Sham group.Compared with the SAH group,the SAH+SB203580 group and the SAH+PD98059 group were increased.Conclusion: The P38 MAPK pathway was activated after subarachnoid hemorrhage,upregulating the expression of pCx43 and pP38 MAPK in the basilar artery,causing CVS.After treatment with the P38 MAPK pathway inhibitor SB203580,Cx43 phosphorylation was reduced and CVS was relieved.Similarly,the ERK pathway was activated after subarachnoid hemorrhage,upregulating the expression of pCx43 and pERK1/2 in the basilar artery,causing CVS.After treatment with the ERK pathway inhibitor PD980590,Cx43 phosphorylation was reduced and CVS was alleviated.