摘要
目的探究甘草酸铵对带状疱疹后遗神经痛(PHN)大鼠脊髓背角小胶质细胞活化,及胰高血糖素样肽-1受体(GLP-1R)/白细胞介素-10(IL-10)/β-内啡肽(β-endorphin)通路的影响。方法将60只大鼠随机分成5组:对照组、模型组、甘草酸铵低剂量组(50 mg/kg)、甘草酸铵中剂量组(100 mg/kg)和甘草酸铵高剂量组(200 mg/kg),每组12只。除对照组外,其余各组均用树脂毒素(RTX)诱导,构建PHN大鼠模型,并进行相应的药物处理。检测各组大鼠对机械刺激和热刺激的敏感性;免疫荧光检测大鼠脊髓背角组织小胶质细胞的活化;ELISA法检测脊髓背角中炎症因子肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)水平;Western blot法检测大鼠脊髓背角中GLP-1R、IL-10、β-endorphin蛋白表达水平。结果与对照组相比,模型组大鼠缩爪热潜伏期(PWTL)值、小胶质细胞活化数量、IL-1β、TNF-α含量、及GLP-1R、IL-10、β-endorphin蛋白水平显著升高(P<0.05),缩爪机械阈值(PWMT)值显著降低(P<0.05);与模型组相比,甘草酸铵各剂量组大鼠PWMT值、小胶质细胞活化数量、GLP-1R、IL-10、β-endorphin蛋白水平显著升高(P<0.05),PWTL值及IL-1β、TNF-α含量显著降低(P<0.05)。结论甘草酸铵可促进PHN大鼠小胶质细胞活化,激活GLP-1R/IL-10/β-内啡肽信号通路,减少促炎细胞因子水平,减轻PHN疼痛反应。
Postherpetic neuralgia(PHN)is a clinical manifestation of varicella-zoster virus reactivation infection and dorsal root ganglion cell damage,and is one of the most common causes of neuropathic pain.This study was performed to investigate the effect of ammonium glycyrrhizinate(AG)on microglia activation in spinal dorsal horn of rats with PHN and its effect on glucagon-like peptide-1 receptor(GLP-1R)/interleukin-10(IL-10)/β-endorphin pathway.A total of 60 rats were recruited as divided randomly into control group,model group,low-dose AG group(50 mg/kg),middle-dose AG group(100 mg/kg)and high-dose AG group(200 mg/kg),with 12 rats in each group.Except for the control group,the other groups were induced by resin toxin(RTX)to construct PHN rat model,and the corresponding drug treatment was carried out.The sensitivity of mechanical stimulation and thermal stimulation was detected.Immunofluorescence was used to detect the activation of microglia in the dorsal horn of the rat spinal cord;ELISA method was used to detect the levels of inflammatory factors TNF-αand IL-1β;Western blot was used to detect the expression levels of GLP-1R,IL-10 andβ-endorphin.Compared with control group,the model group demonstrated higher levels of PWTL value,activated number of microglia,contents of IL-1βand TNFα,and protein levels of GLP-1R,IL-10 andβ-endorphin(P<0.05),but lower level of PWMT value(P<0.05).Compared with model group,the PWMT value,activated number of microglia,protein levels of GLP-1R,IL-10 andβ-endorphin were increased in glycyrrhizin groups(P<0.05),and the PWTL value,contents of IL-1βand TNF-αwere decreased(P<0.05).In conclusion,AG can promote the activation of microglia in PHN rats,activate GLP-1R/IL-10/β-endorphin signaling pathway,reduce levels of pro-inflammatory cytokines and relieve the pain response of PHN rats.
作者
常成
宋燕
CHANG Chen;SONG Yan(Department of Pain,Urumqi Friendship Hospital,Urumqi 830000,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2022年第1期81-87,共7页
Immunological Journal
基金
新疆维吾尔自治区自然科学基金(2017D01C181)。