Exendin-4 Plays A Protective Role In A Rat Model Of Spinal Cord Injury Through SERCA2

Objective 1.explore the mechanism of Exendin-4 on spinal cord injury.2.explore the role of SERCA2 in the rat SCI model,and provide preliminary work for clinical medication of spinal cord injury.Methods1.explore the signaling pathway of Exendin-4 in the role of neurons in SERCA2To determine the effect of Exendin-4 on the expression of SERCA2 through the c AMP/PKA signaling pathway,all PC 12 cells were divided into four groups,group sham,group Exendin-4,PKI group,and PKI+Exendin-4 group.The protein in the extract was determined by Western blot.2.explore the effect of SERCA2 on spinal cord injury in rats and drug intervention of Exendin-4.The aim of this study is to investigate the protective effects and anti apoptotic effects of SERCA2 on SCI.Including the following experimental studies:(1)SERCA2 expression was detected by immunofluorescence and immunoblotting,and the relationship between the role of SERCA2 and apoptosis in rats with spinal cord injury was analyzed.(two)the expression of SERCA2 was detected by immunofluorescence and Western blotting,and the effect of c AMP/PKA on SERCA2 was verified.(three)to clarify the therapeutic effect of Exendin-4 on animal models of spinal cord injury in rats.Results1.Exendin-4 affects the SERCA2 through the PKA signaling pathway.After blocking the activation of PKA in PC 12 cells,Exendin-4 treatment did not increase the level of SERCA2 expression.Compared with the sham group,the simple Exendin-4 treatment could promote the expression of SERCA2 in PC12 cells(P < 0.05),and the PKA and SERCA2 expressions in PKI and PKI +Exendin-4 groups were significantly decreased(P < 0.01).2.Exendin-4 promotes SERCA2 expression and protects spinal cord injury in rats.The results of immuno imprint detection showed that the expression of apoptotic protein caspase-3 in the spinal cord increased significantly after blocking SERCA2,and the expression level of SERCA2 and anti apoptotic protein Bcl-2 decreased significantly(P < 0.01).Immunofluorescence staining and TUNEL staining showed that the positive rate of SERCA2 was decreased after inhibition of SERCA2(P < 0.01),and the positive rate of SCI apoptosis was increased(P < 0.01).After blocking c AMP/PKA,SERCA2 expression decreased(P < 0.01).The goodness of fit analysis showed that: 50% the maximum effective concentration(EC50)was 2.15 g/.100% the maximum effective dose was about 10 g / only.Exendin-4 treatment increased the expression level of c AMP/PKA and SERCA2(P < 0.01).The expression level of Bcl-2 increased significantly(P < 0.01),and the expression level of Caspase-3 decreased(P < 0.01),and the number of TUNEL positive cells decreased(P < 0.01).At the same time,the morphology of spinal cord tissue and the motor function score of rats were improved.ConclusionsThese results suggest that Exendin-4 plays a protective role in a rat SCI model by promoting the up-regulation of SERCA2 protein,reducing cell apoptosis and improving the score of motor function and pathological changes.SERCA2 can serve as a therapeutic target for spinal cord injury in rats and provide an effective treatment strategy for spinal cord injury.