Oridonin alleviates d‐GalN/LPS‐induced acute liver injury by inhibiting NLRP3 inflammasome
Oridonin alleviates d‐GalN/LPS‐induced acute liver injury by inhibiting NLRP3 inflammasome
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DOI：
10.1002/ddr.21776
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发表时间：
2020-12
影响因子：
3.8
通讯作者：
Tao Zhang;Yulian Chen;Zhikun Zhan;Zhihao Mao;Yunman Wen;Shuwen Liu;Lan Tang
中科院分区：
文献类型：
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作者：
Tao Zhang;Yulian Chen;Zhikun Zhan;Zhihao Mao;Yunman Wen;Shuwen Liu;Lan Tang
急性肝损伤（ALI）是一种严重的综合征，与高死亡率相关，但很少有有效的治疗方法。NLRP 3炎性体的激活与ALI的发生有关。冬凌草甲素是一种具有抗炎作用的天然物质，据报道是NLRP 3的抑制剂。本研究的目的是研究冬凌草甲素对d-半乳糖胺（d-GalN）/脂多糖（LPS）诱导的ALI的保护作用，以及该作用是否由NLRP 3介导。用冬凌草甲素（5或10 mg/kg）预处理小鼠3天。然后，它们被注射d-GalN（400 mg/kg）和LPS（40 μg/kg）。通过RT-PCR、Western blot和酶联免疫吸附试验测定炎症因子水平。我们证实了冬凌草甲素显著减轻d-GalN/LPS诱导的小鼠ALI。冬凌草甲素通过降低炎性细胞因子的水平，显著降低炎症反应。更重要的是，冬凌草甲素显著降低NLRP 3、caspase-1、IL-18和IL-1β的表达。本研究表明，冬凌草甲素对d-GalN/LPS诱导的ALI具有保护作用，其机制可能与抑制NLRP 3炎症通路有关。
Acute liver injury (ALI) is a serious syndrome that is associated with high mortality, but there are few effective treatments. The activation of NLRP3 inflammasome is associated with ALI. Oridonin is a natural substance with an anti‐inflammatory effect and has been reported to be an inhibitor of NLRP3. The aim of this study was to investigate the protective effect of oridonin on d‐galactosamine (d‐GalN)/lipopolysaccharide (LPS)‐induced ALI and whether the effect is mediated by NLRP3. Mice were pretreated with oridonin (5 or 10 mg/kg) for 3 days. Then, they were injected with d‐GalN (400 mg/kg) and LPS (40 μg/kg). The levels of inflammatory factors were measured by RT‐PCR, Western blot, and enzyme‐linked immunosorbent assay. We confirmed that oridonin significantly alleviated ALI induced by d‐GalN/LPS in mice. Oridonin markedly decreased the inflammatory response by reducing the levels of inflammatory cytokines. More importantly, oridonin markedly reduced the expression of NLRP3, caspase‐1, IL‐18, and IL‐1β. This study showed that oridonin has a protective effect on d‐GalN/LPS‐induced ALI, and the underlying mechanisms may be associated with the inhibition of the NLRP3 inflammatory pathways.