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王 敏.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[J].中国比较医学杂志,2020,30(6):62~68.
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
投稿时间:2019-12-23  
DOI:10. 3969 / j.issn.1671-7856. 2020. 06. 009
中文关键词:  复方甘草酸苷  实验性自身免疫性脑脊髓炎  JAK/ STAT 信号通路  RORγt  Foxp3
英文关键词:compound glycyrrhizin  experimental autoimmune encephalomyelitis  JAK/ STAT pathway  RORγt  Foxp3
基金项目:
作者单位E-mail
王 敏 西南医科大学附属医院神经内科,四川 泸州 646000 1213772596@ qq.com 
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中文摘要:
      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。
英文摘要:
      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.
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