| Background Neonatal hypoxic-ischemia encephalopathy(HIE)is usually caused by Perinatal asphyxia after interruption of blood flow and oxygen of brain injury and its pathogenesis is a complex pathological process.The severity of brain damage,duration,the timing of the prenatal damage is difficult to define at present accurately.HIE is one of the biggest threat for perinatal newborn[1-2].In recent years,Neonatal critical care have made great progress,but the incidence of HIE is still high,and survivors of the patients live with different degrees of neurological complications and even death[3] for the family and society.There is no effective methods in the treatment of neonatal HIE currently.The pathogenesis progress in HIE is not very clear.Inflammatory cytokines(cytokines and chemokines)participated in the pathological process of HIE,and play a very important role in the pathogenesis of HIE.Due to the lack of effective treatments currently in HIE,there is still need to explore the pathogenesis of HIE and possible treatment methods.Ubiquitin carboxy-terminal hydrolase L1(UCHL1)is involved in the pathogenesis of neurons after injury,and the protein for neuron survival played an important role after ischemia hypoxia.Inflammation plays a vital role of the in the pathological process of HIE,and now there isfew related literature reports about UCHL1 involved in regulating inflammation after brain damage.Therefore,the purpose of this study was to explore the role of ubiquitin carboxy-terminal hydrolase L1(UCHL1)in hypoxic-ischemic brain damage and the effect of UCHL1 on expression of inflammatory cytokines(interleukin-6,IL-6;interleukin-10,IL-10;tumor necrosis factor alpha,TNF-?).Objective To explorethe role of ubiquitin carboxy-terminal hydrolase L1(UCHL1)in hypoxic-ischemic brain damage and the effect of UCHL1 on expression of inflammatory cytokines(interleukin-6,IL-6;interleukin-10,IL-10;tumor necrosis factor alpha,TNF-?).Methods Seven-day postnatal SD rats(40)were randomly divided into control group(20)and hypoxia-ischemia(HI)group(20).The HI group was given hypoxic-ischemic dispose to establish hypoxic-ischemic brain damage(HIBD)animal model,and control group would not be processing.PC12 cell were used to establish oxygen-glucose deprivation(OGD)cell model.PC12 cells were divided into: normal control group,OGD group,LDN(namely LDN-57444,inhibitor for UCHL1)+OGD group,UCHL1 +OGD group.Each group processing factors: normal control group: normal condition;OGD group: oxygen and glucose were deprived in cell culture medium without UCHL1 proteins or LDN pretreatment;LDN+OGD group: LDN pretreatment 2h prior to OGD processing,and then OGD processing for 4h;UCHL1+OGD group: UCHL1 pretreatment 2h prior to OGD processing,and then OGD processing for 4h.Immunohistochemical method was uesd to detect UCHL1 expression in rat brain at 6 h and 24 h.Hoeschst 33258 staining method wae used to detect apoptosis of PC12 cells at 24 h,48 h,72 h.ELISA kits was uesd to detect concentration of IL-6,IL-10,the TNF-?,UCHL1 in PC12 cell supernatant at 24 h,48 h,72 h.SPSS17.0 statistical software was used for data processing.Results UCHL1 in HI group expressed higher than normal control group.The apoptosis level of PC12 cells each wasdifferentat the same time.Compared with control group,expression of TNF alpha increased in OGD group and LDN+OGD group at 24 h,48 h,72 h(P < 0.05);Compared with OGD group,expression level of TNF-?increased in LDN+OGD group at 24 h,48 h,72 h(P<0.05),and expression of TNF-?decresaed in UCHL1 + OGD group at 24 h,48 h,72 h(P<0.05).Compared with control group,expression of IL-6 increased in OGD group at 72 h(P<0.05),expression of IL-6 were higher in LDN+OGD group than that in control group at 24 h,48h,72h(P<0.05);Compared with OGD group,IL-6 expressed higher in LDN+ OGD group at 24 h,48h,72h(P<0.05);Compared with OGD group,expression level of IL-6 decreased in UCHL1+OGD group at 24 h,48h(P< 0.05).Compared with control group,expression level of IL-10 in OGD group increased at 24 h,48 h(P<0.05),expression of IL-10 increased in LDN+OGD group at 24 h,48h,72h(P < 0.05);Compared with OGD group,IL-10 expressed lower in LDN+OGD group at 24 h,48 h,72 h(P<0.05);Compared with OGD group,expression of IL-10 increased in UCHL1+OGD group at 24 h,48h(P< 0.05).Compared with control group,expression level of UCHL1 in OGD group increased at 24 h,48 h,72 h(P<0.05);Compared with OGD group,UCHL1 expressed higher in LDN+OGD group at 24 h,48h(P<0.05).Conclusion UCHL1 plays a vital role for the survival of the neurons after HIBD.UCHL1 is protective for neurons for after HIBD.The mechanism of brain protection of UCHL1 may be by downgrgulating the expression of TNF-?and IL-6 and upregulating the expression of IL-10. |
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