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    刘迪迪, 陆莉, 杨燕青, 王凤超. 桑黄酮抑制NLRP3炎症小体活化并缓解感染性休克的作用研究[J]. 蚌埠医科大学学报, 2023, 48(1): 72-76. DOI: 10.13898/j.cnki.issn.1000-2200.2023.01.014
    引用本文: 刘迪迪, 陆莉, 杨燕青, 王凤超. 桑黄酮抑制NLRP3炎症小体活化并缓解感染性休克的作用研究[J]. 蚌埠医科大学学报, 2023, 48(1): 72-76. DOI: 10.13898/j.cnki.issn.1000-2200.2023.01.014
    shu
    LIU Di-di, LU Li, YANG Yan-qing, WANG Feng-chao. Effect of mulberrin on inhibiting the activation of NLRP3 inflammasome and relieving infectious shock[J]. Journal of Bengbu Medical University, 2023, 48(1): 72-76. DOI: 10.13898/j.cnki.issn.1000-2200.2023.01.014
    Citation: LIU Di-di, LU Li, YANG Yan-qing, WANG Feng-chao. Effect of mulberrin on inhibiting the activation of NLRP3 inflammasome and relieving infectious shock[J]. Journal of Bengbu Medical University, 2023, 48(1): 72-76. DOI: 10.13898/j.cnki.issn.1000-2200.2023.01.014
    shu

    桑黄酮抑制NLRP3炎症小体活化并缓解感染性休克的作用研究

    Effect of mulberrin on inhibiting the activation of NLRP3 inflammasome and relieving infectious shock

      摘要
    • 摘要:
      目的探究桑枝提取物桑黄酮对NLRP3炎症小体活化的影响, 为相关炎性疾病的治疗提供新思路。
      方法在细胞水平上, 使用Western blotting和ELISA方法, 检测小鼠骨髓来源的巨噬细胞(BMDM)和人THP-1细胞在尼日利亚菌素、单钠尿酸盐和腺嘌呤核苷三磷酸(ATP)3种刺激剂诱导下的半胱氨酸蛋白酶-1(Caspase-1)和白细胞介素(IL)-1β表达水平。在动物实验中, 构建脂多糖(LPS)诱导的感染性休克模型, 将实验小鼠分为安慰剂组、感染性休克组和桑黄酮干预组, 利用ELISA检测小鼠腹腔灌洗液及血清中IL-1β和肿瘤坏死因子-α(TNF-α)水平。
      结果在BMDM和THP-1细胞中, 桑黄酮可以抑制尼日利亚菌素、单钠尿酸盐和ATP这3种炎症小体激动剂诱导的Caspase-1和IL-1β的加工和成熟(P < 0.01), 而对非炎症小体相关的细胞因子TNF-α的分泌无影响(P>0.05)。在动物实验中, 发现桑黄酮可以缓解LPS诱导的小鼠感染性休克(P < 0.01), 明显抑制LPS诱导的小鼠血清及腹腔液中IL-1β的表达(P < 0.01), 延长LPS造模后小鼠的存活时间(P < 0.01)。
      结论桑黄酮作为一种中草药活性成分提取物, 可以在体外和体内抑制NLRP3炎症小体的活化, 为NLRP3相关疾病的治疗提供了实验依据。

       

      Abstract:
      ObjectiveTo investigate the effect of mulberrin, a Chinese herbal extract, on NLRP3 inflammasome activation, and provide new insight for NLRP3-related disease.
      MethodsWestern blotting and ELISA were used to detect the expression level of caspase-1 and interleukin-1β of mouse bone marrow derived macrophages (BMDM) and human THP-1 cells induced by three agonists: Nigerian bacteriocin, monosodium urate and adenosine triphosphate (ATP).Mouse septic shock model induced by lipopolysaccharide (LPS) was constructed, and experimental mice were divided into placebo group, septic shock group and mulberrin treatment group.The levels of IL-1β and TNF-α in intraperitoneal lavage fluid and serum were detected by ELISA.
      ResultsIn vitro experiments, we found that the processing and maturation of caspase-1 and IL-1β induced by three classic inflammasome agonists (Nigericin, MSU and ATP) were inhibited by mulberrin in BMDM and THP-1 cells (P < 0.01).However, there was no obviously difference observed on the secretion of non-inflammasome-related cytokines, such as TNF-α (P>0.05).In vivo experiments, mulberrin treatment alleviated septic shock, significantly inhibited IL-1β expression in serum and intraperitoneal lavage fluid of mice, and prolonged the survival time of LPS-induced mice(P < 0.01).
      ConclusionsAs an active ingredient of Chinese herb extract, mulberrin can inhibit the NLRP3 inflammasome activation in vitro and in vivo.Our study provide experimental evidences for the treatment of NLRP3-related diseases.

       

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