摘要
目的:探讨丙戊酸钠(VPA)通过下调钙钠交换蛋白(NCX)表达对大鼠神经病理性疼痛(NP)的影响。方法:实验分为假手术组、模型组、VPA组、VPA+E4031组,每组10只;除假手术组外,其余各组建立坐骨神经慢性压迫损伤(CCI)致NP模型,分别于造模前,建模后的第1、3、5、7、10天测定机械缩足反射阈值(MWT)和缩足反射潜伏期(PWTL)。建模后第14天,ELISA实验检测脊髓中TNF-α、IL-1β水平;实时荧光定量PCR(qRT-PCR)和Western blot检测背根神经节(DRG)中HDAC1、HDAC2、HDAC3、HDAC8、NCX mRNA和蛋白水平。结果:造模前,4组MWT、PWTL差异无统计学意义(P>0.05)。建模后第1、3天,与假手术组相比,模型组、VPA组、VPA+E4031组MWT、PWTL降低(P<0.05)。建模后第5、7、10天,与假手术组相比,模型组MWT、PWTL降低(P<0.05);与模型组相比,VPA组MWT、PWTL升高(P<0.05);与VPA组相比,VPA+E4031组MWT、PWTL降低(P<0.05)。建模后第14天,与假手术组相比,模型组脊髓中TNF-α、IL-1β水平,DRG中HDAC1、HDAC2、NCX mRNA和蛋白水平,HDAC3蛋白水平升高(P<0.05);与模型组相比,VPA组脊髓中TNF-α、IL-1β水平,DRG中HDAC1、HDAC2、HDAC3、NCX mRNA和蛋白水平降低(P<0.05);与VPA组相比,VPA+E4031组脊髓中TNF-α、IL-1β水平,HDAC1、HDAC2、NCX mRNA和蛋白水平,HDAC3、HDAC8蛋白水平升高(P<0.05)。结论:VPA可下调NCX表达缓解炎症水平,从而缓解大鼠的NP。
Objective:To investigate the effect of sodium valproate(VPA)on neuropathic pain(NP)in rats by down-regulating the expression of sodium-calcium exchanger(NCX).Methods:The experiment was divided into sham operation group,model group,VPA group and VPA+E4031 group,with 10 rats in each group;except for the sham operation group,the NP model induced by chronic compression injury of sciatic nerve(CCI)was established in the other groups,and the mechanical foot retraction threshold(MWT)and paw retraction latency(PWTL)were measured before modeling and 1 st,3 rd,5 th,7 th,10 th day after modeling.On the 14 th day after modeling,the levels of TNF-αand IL-1βin spinal cord were detected by ELISA;in addition,the mRNA and protein levels of HDAC1,HDAC2,HDAC3,HDAC8 and NCX in dorsal root ganglion(DRG)were detected by real-time fluorescence quantitative PCR(qRT-PCR)and Western blot.Results:Before modeling,there was no significant difference in MWT and PWTL among the four groups(P>0.05).On the 1 st and 3 rd day after modeling,MWT and PWTL in model group,VPA group and VPA+E4031 group were lower than those in sham operation group(P<0.05).On the 5 th,7 th,10 th day after modeling,MWT and PWTL in the model group were lower than those in the sham operation group(P<0.05);MWT and PWTL in VPA group were higher than those in the model group(P<0.05);MWT and PWTL in VPA+E4031 group were lower than those in the VPA group(P<0.05).On the 14 th day after modeling,compared with the sham operation group,the levels of TNF-αand IL-1βin spinal cord,the mRNA and protein levels of HDAC1,HDAC2,NCX and HDAC3 protein in DRG of model group were increased(P<0.05);compared with those in the model group,the levels of TNF-αand IL-1βin spinal cord,mRNA and protein levels of HDAC1,HDAC2,HDAC3 and NCX in DRG in VPA group were significantly lower(P<0.05);in addition,compared with those in VPA group,the levels of TNF-αand IL-1βin spinal cord,mRNA and protein levels of HDAC1,HDAC2 and NCX,the protein levels of HDAC3 and HDAC8 in VPA+E4031 group were significant
作者
徐梅玲
申大年
张育珠
XU Meiling;SHEN Danian;ZHANG Yuzhu(Department of Pain,the Fifth People's Hospital of Qinghai Province,Xining 810007,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2022年第1期22-27,共6页
Chinese Journal of Immunology
