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薯蓣皂苷通过抑制 NF-κB 激活和 NLRP3 炎症小体减轻 NZB/W F1 小鼠狼疮肾炎。

Dioscin attenuates lupus nephritis in NZB/W F1 mice by decreasing NF-κB activation and NLRP3 inflammasome.

机构信息

Department of Nephrology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, China.

Department of Geriatrics, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, China.

出版信息

Folia Histochem Cytobiol. 2024;62(2):110-121. doi: 10.5603/fhc.100604. Epub 2024 Jul 23.

Abstract

INTRODUCTION

Dioscin, a natural steroid saponin, has anticancer, anti-inflammatory, anti-hyperlipidemic, and glycemic capabilities. This study focused on dioscin roles and its related mechanisms in experimental lupus nephritis.

MATERIALS AND METHODS

Lupus-prone NZB/W F1 mice were intragastrically administered with dioscin, prednisone or vehicle, and kidney, urine and blood samples were harvested after the mice were sacrificed. Proteinuria, blood urea nitrogen (BUN), creatinine, anti-dsDNA, IL-1β, and IL-18 levels in serum as well as IFN-γ, IL-6, IL-17 and TNF-α levels in kidney tissues were assessed. Renal histopathology was examined through hematoxylin-eosin staining. IgG and C3 expression in kidney was evaluated using immunofluorescence staining. The number of glomerular F4/80-positive cells and NLRP3-positive cells was determined by immunohistochemical staining. The protein expression was examined by western blotting.

RESULTS

Dioscin alleviated lupus nephritis in NZB/W F1 mice. Dioscin declined serum anti-dsDNA level, prevented deposition of immune complexes in renal glomeruli, and inhibited the inflammatory response and infiltration of macrophages into mouse kidneys. Dioscin inhibited NF-κB and NLRP3 inflammasome in NZB/W F1 mice.

CONCLUSIONS

Dioscin ameliorates lupus nephritis through inhibition of NLRP3 inflammasome and NF-κB signaling.

摘要

简介

薯蓣皂苷元是一种天然甾体皂苷,具有抗癌、抗炎、抗高血脂和降血糖的作用。本研究主要关注薯蓣皂苷元在实验性狼疮肾炎中的作用及其相关机制。

材料和方法

将狼疮易感 NZB/W F1 小鼠用薯蓣皂苷元、泼尼松龙或载体灌胃,在处死小鼠后采集肾脏、尿液和血液样本。评估血清中蛋白尿、血尿素氮(BUN)、肌酐、抗 dsDNA、IL-1β 和 IL-18 水平以及肾组织中 IFN-γ、IL-6、IL-17 和 TNF-α 水平。通过苏木精-伊红染色检查肾组织病理学变化。用免疫荧光染色评估 IgG 和 C3 在肾脏中的表达。通过免疫组织化学染色确定肾小球 F4/80 阳性细胞和 NLRP3 阳性细胞的数量。通过 Western 印迹检查蛋白表达。

结果

薯蓣皂苷元减轻了 NZB/W F1 小鼠的狼疮肾炎。薯蓣皂苷元降低了血清抗 dsDNA 水平,防止了免疫复合物在肾小球中的沉积,并抑制了炎症反应和巨噬细胞浸润到小鼠肾脏中。薯蓣皂苷元抑制了 NZB/W F1 小鼠中的 NF-κB 和 NLRP3 炎性小体。

结论

薯蓣皂苷元通过抑制 NLRP3 炎性小体和 NF-κB 信号通路改善狼疮肾炎。

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