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杏鲍菇对 P2X7R-NLRP3 炎性小体激活的抑制作用:在酒精性脂肪性肝炎中可能具有保护作用。

Inhibition of P2X7R-NLRP3 Inflammasome Activation by Pleurotus citrinopileatus: A Possible Protective Role in Alcoholic Hepatosteatosis.

机构信息

Key Laboratory for Natural Resource of Changbai Mountain and Functional Molecules, Ministry of Education, College of Pharmacy , Yanbian University , Yanji , Jilin 133002 , People's Republic of China.

Analysis Center , Dt&CRO, Incorporated , Yongin-si , Gyeonggi-do 17042 , Republic of Korea.

出版信息

J Agric Food Chem. 2018 Dec 19;66(50):13183-13190. doi: 10.1021/acs.jafc.8b05756. Epub 2018 Dec 10.

DOI:10.1021/acs.jafc.8b05756
PMID:30497264
Abstract

Pleurotus citrinopileatus (golden oyster mushroom) is a widely used edible mushroom. We investigated the inhibitory effect of P. citrinopileatus aqueous extract against alcoholic steatohepatitis and its underlying mechanism. Acute and chronic ethanol-feeding murine models were established by intragastrically administering ethanol or feeding an ethanol-containing Lieber-DeCarli liquid diet to male C57BL/6 mice. In both models, P. citrinopileatus decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), and hepatic TG levels. Hematoxylin and eosin (HE) and Oil Red O staining confirmed that P. citrinopileatus ameliorated both acute and chronic alcoholic hepatosteatosis, characterized by regulation of lipid-metabolism-related proteins, including sirtuin 1 (SIRT1), AMP-activated kinase (AMPK), and sterol regulatory element-binding protein (SREBP1). P. citrinopileatus reversed inflammatory response via modulating purinergic receptor P2X ligand-gated ion channel 7 (P2X7R)-NOD-like receptor pyrin domain 3 (NLRP3) inflammasome. P. citrinopileatus restored the expressions of those proteins to a normal level. In addition, HepG2 cells were incubated with P. citrinopileatus prior to ethanol stimulation. P. citrinopileatus reduced ethanol exposure-induced lipid deposition. Concomitantly, P. citrinopileatus increased AMPK and SIRT1 expressions, which were reduced by ethanol treatment. P. citrinopileatus ameliorated alcoholic hepatic steatosis and accompanied inflammatory response via regulating SIRT1-AMPK and P2X7R-NLRP3 inflammasome activation, highlighting a promising strategy and utility of P. citrinopileatus for alcoholic steatohepatitis as dietary health supplements.

摘要

金黄银耳(黄金菇)是一种广泛使用的食用菌。我们研究了金黄银耳水提取物对酒精性脂肪性肝炎的抑制作用及其机制。通过灌胃给予乙醇或给予含乙醇的 Lieber-DeCarli 液体饮食,建立急性和慢性乙醇喂养的雄性 C57BL/6 小鼠模型。在这两种模型中,金黄银耳均降低了血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、甘油三酯(TG)和肝 TG 水平。苏木精和伊红(HE)及油红 O 染色证实,金黄银耳改善了急性和慢性酒精性脂肪性肝炎,其特征是调节脂质代谢相关蛋白,包括沉默调节蛋白 1(SIRT1)、AMP 激活的蛋白激酶(AMPK)和固醇调节元件结合蛋白 1(SREBP1)。金黄银耳通过调节嘌呤能受体 P2X 配体门控离子通道 7(P2X7R)-NOD 样受体吡啶结构域 3(NLRP3)炎性小体来逆转炎症反应。金黄银耳将这些蛋白的表达恢复到正常水平。此外,将 HepG2 细胞用金黄银耳孵育后再用乙醇刺激。金黄银耳减少了乙醇暴露诱导的脂质沉积。同时,金黄银耳增加了 AMPK 和 SIRT1 的表达,而乙醇处理则降低了它们的表达。金黄银耳通过调节 SIRT1-AMPK 和 P2X7R-NLRP3 炎性小体的激活,改善了酒精性肝脂肪变性和伴随的炎症反应,突出了金黄银耳作为饮食保健品治疗酒精性脂肪性肝炎的有前途的策略和应用。

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