The Role And Mechanism Of MSK1 In Repair Of Spinal Cord Injury In Rats

Objective To investigate the change rules of expressing time in term of mitogen and the stress-activated protein kinases after Spinal cord injury(SCI)on rats,and further analysis were made on its effect and possible mechanism in proliferation repairing after Spinal cord injury in order to explore and provide the experimental evidence for potential interfering target spot on Spinal cord injury.Method Spinal cord injury model of rats(Allen's model)were set up by using NYU Impactor-III striking utensils.The male grown SD rats were randomly grouped into Normal,Sham-operation(Sham-group,including 8h,12 h,1d and 2d,3d,5d,7d group),Operation(SCI-group,including 8h,12 h,1d and 2d,3d,5d,7d group).In each group respectively,we examined the motor function by Basso,Beattie,Bresnahan(BBB)locomotor rating scale,neurons morphologic change were observed through HE staining,the expression of MSK1 and PCNA(index of the status of reactive neurogliocyte proliferation)were measured by real-time fluorescence quantification PCR as well as protein immunoblotting.Result BBB score : the hind limb motor function was disappeared immediately after spinal cord injury,and was completely paralyzed,which was in 3d.The score was still sianificantly less than the Sham group at day 7.HE staining: morphological structure of spinal cord was normal in both Normal and Sham groups,while SCI groups developed into widespread neuronal dissolution and necrosis,with the trend of decreasing in number and plenty of inflammatory cell infiltration.Real-time fluorescence quantification PCR: the expression of MSK1 increased a little at 8h after injury,then progressively decreased from 12 h,peaked at day3(P<0.05),and then gradually returned to normal level.The m RNA expression of MSK1 showed an obvious change after spinal cord injury,which had a negative correlation with PCNA.Immunoblotting detection: the expression of MSK1 did not show an increase at 8h after spinal cord injury.Besides,they were in accordance with the gene level in term of variation tendency.At protein level,the changes of PCNA were also on the contrary,which indicated that MSK1 may play an certain role in the proliferation of spinal cord injury rats.Signal pathway correlation analysis: MSK1 is involved in cell cycle regulation by ERK1 / 2 signal transduction pathway(classical MAPK signal transduction pathway)in addition to p38 MAPK signal transduction pathway.JNK,P38 MAPK signal transduction pathway has some relations with PCNA by regulating the P53 signaling pathway,thus participating in the regulation of cell cycle.The key sites of regulation is cyclin-dependent protein kinase 4/6(CDK4/6)and cyclin D(Cyc D)of the formed composite,which happens to be the key cells from the G0 phase to the G1 phase.Conclusion First,MSK1 may have a certain effect on the recovery of motor function in rats after spinal cord injury.Then,MSK1 may have some suppressing effect on proliferation of neurogliocyte,but the specific mechanism needs further study.