白芍总苷抑制NLRP3活化治疗干燥综合征的实验研究
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1.南京中医药大学中西医结合鼓楼临床医学院;2.南京医科大学鼓楼临床医学院

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国家自然科学基金面上项目(81970062), 南京市医学科技发展资金项目(ZKX21027)


Total glucosides of paeony inhibited NLRP3 inflammasome activation for treatment of mice with Sj?gren's syndrome
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    摘要:

    目的 干燥综合征是累及外分泌腺的慢性炎症性自身免疫病,目前临床缺乏效果好且副作用少的药物。文章旨探讨白芍总苷(Total glucosides of paeony,TGP)治疗干燥综合征的效果及与抑制NLRP3炎症体活化的关系,旨在阐明TGP治疗干燥综合征的新机制。方法 选取雌性非肥胖性糖尿病(non-obese diabetic,NOD)小鼠为干燥综合征的模型;TGP(400mg·kg-1)灌胃1个月后,测量小鼠唾液流量;观察颌下腺组织淋巴细胞浸润情况;检测脾脏细胞NLRP3炎症体活化状态。体外刺激脾脏细胞NLRP3炎症体活化,并用100ug/ml TGP处理。RT-qPCR和Western blot法检测脾脏细胞NLRP3炎症体活化状态。结果 与对照组相比,TGP灌胃组小鼠唾液流量显著增加(P<0.05);颌下腺组织淋巴细胞浸润显著减少;脾脏细胞的NLRP3炎症体表达水平显著下降(P<0.05);体外实验也表明,TGP抑制脾脏细胞的炎症体活化(P<0.05);结论 TGP改善干燥综合征小鼠症状,其机制与抑制NLRP3炎症体的活化相关。我们的研究结果揭示了TGP治疗干燥综合征的新机制,为进一步推广应用TGP治疗干燥综合征患者提供了新的证据。

    Abstract:

    Objective: The efficacy of total glucosides of paeony (TGP) in the treatment of Sj?gren's syndrome (SS) and its relationship with inhibition of NLRP3 inflammasome activation were investigated, so as to clarify the novel mechanisms of TGP on treatment of SS. Methods: Female non-obese diabetic (NOD) mice were selected as the model of SS. The NOD mice were intragastric administrated with TGP (400mg·kg-1)for 1 month. The saliva flow rates of mice were measured. The lymphocyte infiltration in submandibular gland was determined. The NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation of spleen was detected. In vitro, the NLRP3 inflammasome was activated in cultured splenocytes with or without 100ug/ml TGP treatment. Then, the NLRP3 inflammasome activation was determined by RT-qPCR and Western blot. Results: Compared with the mice of control group, the saliva flow rates were significantly increased(P<0.05) and the lymphocyte infiltration in submandibular gland was significantly reduced in NOD mice of TGP treatment group. The NLRP3 inflammasome of spleen was inhibited in NOD mice with TGP treatment(P<0.05). In vitro, the NLRP3 inflammasome activation of splenocytes was also suppressed by TGP(P<0.05). Conclusion: Our results showed that TGP alleviated SS-like symptoms in NOD mice and these beneficial effects were related to inhibition of NLRP3 inflammasome activation. Our findings not only uncovered the novel mechanisms of therapeutic effects of TGP in SS, but also provided new evidences for application of TGP in treatment of SS patients.

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  • 收稿日期:2023-02-22
  • 最后修改日期:2023-04-20
  • 录用日期:2023-10-25
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