基于JAK2/STAT3/SOCS3信号通路探讨复方甘草酸苷对实验性自身免疫性脑脊髓炎的防治作用

Intraperitoneal injection of compound glycyrrhizin exerts preventive and therapeutic effects on experimental autoimmune encephalomyelitis via the JAK2/STAT3/SOCS3 signaling pathway

目的探讨复方甘草酸苷(CG)对实验性自身免疫性脑脊髓炎(EAE)小鼠的防治作用及其对JAK2/STAT3/SOCS3信号通路的影响。方法将50只雌性C57BL/6小鼠随机分为5组:空白组、模型组和CG低、中、高剂量干预组,每组10只。模型组和CG各干预组建立EAE模型,干预组分别予以CG低、中、高剂量(15、30、60 mg/(kg·d))腹腔注射,空白组及模型组腹腔注射等体积生理盐水,连续14 d。观察小鼠神经功能缺损评分、病理学改变及程度。采用Western blot法检测脑组织蛋白的表达、实时荧光定量RT-PCR法检测脑组织mRNA的含量。结果与模型组比较,CG各干预组最高神经功能缺损评分(P<0. 05)及累计神经功能缺损评分(P<0. 05)降低,脊髓组织炎性细胞浸润及脱髓鞘程度减轻,JAK2、STAT3蛋白及其mRNA表达下降(P<0. 05),SOCS3蛋白及其mRNA表达升高(P<0. 05),RORγt mRNA表达下降(P<0. 05),Foxp3 mRNA升高(P<0. 05)。结论 CG对EAE小鼠发挥防治作用,其机制可能与负性调控因子SOCS3的表达上调,JAK/STAT信号通路的抑制以及影响Th17/Treg细胞平衡有关。

Objective To investigate the effect of glycyrrhizin compound(CG)on mouse models of experimental autoimmune encephalomyelitis(EAE)via the JAK2/STAT3/SOCS3 signaling pathway.Methods Fifty female C57BL/6 mice were randomly divided into the control group,model group,and high-dose,medium-dose and low-dose CG intervention groups(n=10 mice per group).The model and CG intervention groups established the EAE model.The intervention groups were injected with CG(15 mg/(kg·d),30 mg/(kg·d),or 60 mg/(kg·d))for 14 consecutive days.The control and model groups were simultaneously intraperitoneally injected with equal volumes of saline.The neurological deficit scores and pathological changes in each group were recorded.Western blot was used to detect protein expression in the brain tissue,and real-time fluorescence quantitative RT-PCR was used to detect mRNA expression in the brain tissue.Results Compared with the model group,the highest neurological deficit and cumulative neurological deficit scores were reduced,spinal cord inflammation and demyelination were reduced,JAK2 and STAT3 protein and mRNA expressions were decreased,SOCS3 protein and mRNA expressions were increased,RORγt mRNA expression was decreased,and FOXP3 mRNA expression was increased in all CG groups(all P<0.05).Conclusions CG exerted preventive and therapeutic effects on EAE model mice.The mechanism may be related to upregulation of SOCS3,inhibition of the JAK/STAT signaling pathway,and rectification of the Th17/Treg immune imbalance.