TRPV1介导小胶质细胞自噬在带状疱疹后神经疼痛中的作用和分子机制

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【中图分类号】R741.02 【文献标志码】A
【AbstractObectiveToinvestgatethmechansmoftransientreceptorpotentialvaniloidsufamily(TRPV)-mediatedmicroglia autophagyinpostherpeticneuralgia.Methods:Fortymicewererandomlydividedintocontrol group,postherpeticneuralgia(PHN) group,PHN-sh-NC group,and PHN-sh-TRPV1group,with10 miceineachgroup.Wetested the mice'smechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL);measured serum levelsof tumor necrosis factor-alpha(TNF- α ),interleukin (IL)-1β,IL-6,andbrainderivedeurotroicfactorBD)byee-lnkedimmunosorbentassa;assessdtheforatioofautophagosomesinthespialcord issuesbytransmissonelectronmicroscopy;measuredtheexpressonofmicrotubuleassociaedpro teinllightchain3(LC3)andionizedcalciumbindingadaptormolecule1(Iba-1)inthespinalcordtissesbyimmunofluorescence assay;and determined the protein expression of Beclin-1, microtubule-associatedprotein1lightchain 3B(LC3B),and p62 inthe spinal cordtissuesbyWesternblot.Results:Comparedwith the control group,the PHN group and PHN-sh-NC group had significantdecreasesinMWT,serumBNDF1 evel(t=10.49,P<1 0.001), and p62( P =0.004)protein expression in the spinal cord tissues and significantincreasesin TWL,serum TNF- α (t=26.27, P <0.001), IL-1β(t=17.0,P<0.001),andIL-6levels( ⋅ =25.48,P<0.001),and the expression of Iba-1( P=0.002 ),LC3( P<0.001 ),LC3B( P=0.001. ),and Beclin-1 proteins( P=0.001 )in the spinal cord tissues. ComparedwiththePHNgroup,thePHN-sh-TRPV1grouphadasignificantlyhigherMWT,asignificantlyhigherserumBNDFlevel (t=5.174, P<0.001 ,a significantly higher p62 protein expression level ( P<0.001 )in the spinal cord tissues,a significantly lower TWL, significantly lower serum TNF- α ( t=20.57 P<0.001 ),IL-1β( t=8.260 P<0.001 ),and IL-6 levels( t=19.81 , P<0.001 ),and significantly lower expression levels of Iba-1( P<0.001 ),LC3( P<0.001 ),LC3B( P=0.001 ),andBeclin-1( P<0.001 )in the spinal cord tissues.Conclusion:MirogliautophagyisactivatedinthespnalcordofPHNmice,andsuppressingtheexpressonofTVcannhibit microglia autophagy to relieve pain in PHN mice.
【Key words】TRPV1;microglia autophagy ;postherpetic neuralgia
带状疱疹后神经痛(postherpeticneuralgia,PHN)是一种顽固性神经病理性疼痛疾病,主要症状为自发痛、诱发痛、痛觉过敏等。(剩余11862字)