The Influence Of Monosialoganglioside Co-administration On Bupivacaine-induced Spinal Toxicity Rats And Possible Mechanism

Objects Disscuss if monosialoganglioside(GM-1)co-administration can reduce spinal toxicity induced by 5% bupivacaine and explore the possible mechanism in rats.Methods: All the rats received subarachnoid catheter insertion.Group G received intrathecal GM-1(30mg/kg)injection 24 h prior to bupivacaine injection.Group G+B received GM-1(30mg/kg)immediately prior to bupivacaine.Group B received bupivacaine without GM-1 pretreatment or co-administration.Group saline received intrathecal saline injection only.All the following experients were administered in 6 time points(1.5h,1d,3d,5d,7d,14 d after intrathecal injection).The motor function of rats were evaluated by BBB score,while the sensitive function were represented by TFL and converted into %MPE.The activity and morphology of neuron were accessed by nissl staining.The number of apoptotic neuron is measured by TUNNEL method.The histomorphology of spine were observed by light microscope.The untrastructure of spine were observed by transmission electron microscope.Histological and ultrastructural injury in spine were measured by SD score.The expression level of genes related to IRE1α signal path way(IREα,ASK1,TRAF2,JNK)were detected by RT-PCR,while the quantity of protein related to IRE1α signal pathway(p-IRE1α,ASK1,TRAF2,p-JNK)was detected by immunohistochemistry and western blotting.Results1.In 0.5h,1d,3d,5d,7d,14 d after injection,Group B,Group G and Group G+B showed abnormal neurological function,less living neurons and higher apoptosis rate compared with Group saline at the same time points.2.Compared with Group B,Group G and Group G+B showed lower %MPE since 3d(P<0.05),higher BBB score(P<0.05),more living neurons(P<0.05)and lower apoptosis rate since 5d(P<0.05).3.In all time points after injection,there is no differences between Group G and Group G+B in neurological function,number of living neurons and apoptosis rate(P>0.05).4.Compared with Group saline,both Group B and Group G showed histological and microstructure injury in different degree(leading to higher SD score),higher levels of m RNA(IREα,ASK1,TRAF2,JNK)and protein(p-IRE1α,ASK1,TRAF2,p-JNK)related to IRE1α signal pathway,in all time points after injection.5.Compared with group B,Group G+B had lower SD score and decreased expression of IRE1α signal pathway associated m RNA(IREα,ASK1,TRAF2,JNK)and protein(p-IRE1α,ASK1,TRAF2,p-JNK),since 5d.Conclusion Monosialoganglioside co-administration can reduce spinal toxicity induced by 5% bupivacaine,which is possibly associated to the inhibition of IRE1α signal pathway.