茵陈蒿汤对代谢相关脂肪性肝病小鼠XOD介导NLRP3炎症小体信号通路的影响  

Exploring the effect of Yinchenhao Decoction on the XOD-mediated NLRP3 inflammasome signaling pathway in mice with metabolism-associated fatty liver disease

作　　者：刘宝莹 黄艳阳 杨思琦 沙小钰 贾连群[1] 隋国媛 LIU Bao-ying;HUANG Yan-yang;YANG Si-qi;SHA Xiao-yu;JIA Lian-qun;SUI Guo-yuan(Ministry of Education Key Laboratory of Visceral Manifestation Theory and Application of Traditional Chinese Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学,中医脏象理论及应用教育部重点实验室,辽宁沈阳110847

出　　处：《时珍国医国药》2025年第1期34-39,共6页Lishizhen Medicine and Materia Medica Research

基　　金：沈阳市中青年科技创新人才支持计划项目(RC210094);辽宁省自然科学基金资助项目(2022-MS-283)。

摘　　要：目的基于黄嘌呤氧化酶(XOD)介导NLRP3炎症小体信号通路探讨茵陈蒿汤防治MAFLD的作用机制。方法24只小鼠随机分为空白对照组、模型组和中药干预组。采用HE和油红O染色观察肝脏组织病理形态,全自动生化分析仪检测血脂和肝功能。GPO-PAP法检测肝脏TG水平;比色法检测尿酸水平;可见分光光度法检测肝脏XOD活性;ELISA法检测血清BG、INS及肝脏IL-1β和IL-18水平;实时荧光定量PCR法检测肝脏NLRP3、SREBP-1c、FASN、ACC、SCD1mRNA水平。Western blot法检测肝脏NLRP3、ASC、Caspase-1、IL-1β、IL-18、IRS、p-IRS、SREBP-1c、FASN、ACC、SCD1蛋白表达。结果与空白对照组比较,模型组肝细胞脂肪变性明显,肝脏脂质沉积显著增高;血清TG、TC、AST、LDL-C、HDL-C水平显著升高;HOMA-IR、ISI显著升高;肝脏尿酸、TG、IL-1β、IL-18水平及XOD活性显著升高;肝脏NL⁃RP3、ASC、Caspase-1等蛋白及NLRP3、SREBP-1c、FASN等mRNA表达水平显著升高(P<0.05);与模型组比较,中药干预组肝细胞脂肪变性显著降低,肝脏脂质沉积显著改善;血清TG、TC、AST、ALT、LDL-C水平显著降低;HOMA-IR、ISI显著降低;肝脏尿酸、TG、IL-1β、IL-18水平及XOD活性显著降低;肝脏NLRP3、ASC、Caspase-1等蛋白及NLRP3、SREBP-1c、FASN等mRNA表达水平显著降低(P<0.05)。结论茵陈蒿汤可能通过XOD介导NLRP3炎症小体信号通路调节肝脏TG合成,从而抑制MAFLD发生发展。Objective To explore the mechanism of Yinchenhao Decoction(YCHD)in preventing and treating metabolism-associated fatty liver disease(MAFLD)based on the NLRP3 inflammasome signaling pathway mediated by XOD.Methods Twenty-four mice were randomly divided into the blank control group,the model group and the drug intervention group.HE and Oil Red O staining were used to observe the histopathological morphology of liver,and automatic biochemical analyzer(ACA)was used to detect blood lipid and liver function.The GPO-PAP method was used to detect the levels of TG in the liver,colorimetry to detect the levels of uric acid,visible spectrophotometry to detect XOD activity in the liver,ELISA to detect the levels of serum BG,INS and the levels of IL-1β and IL-18 in the liver,and real-time fluorescence quantitative PCR to detect the levels of NLRP3,SREBP-1c,FASN,ACC and SCD1mRNA in the liver.In addition,Western blot(WB)was utilized to detect the expressions of NLRP3,ASC,Caspase-1,IL-1β,IL-18,IRS,p-IRS,SREBP-1c,FASN,ACC,and SCD1 proteins in the liver.Results Compared with the blank control group,hepatocyte steatosis and lipid deposition were significantly increased in the model group.Serum levels of TG,TC,AST,LDL-C and HDL-C,HOMA-IR and ISI,and the levels of uric acid,TG,IL-1β,IL-18 and XOD activity in the liver were all significantly increased.The levels of NLRP3,ASC,Caspase-1 and NLRP3,SREBP-1c,FASN mRNA expression levels in the liver were significantly increased(P<0.05).Compared with the model group,hepatocyte steatosis was significantly reduced and hepatic lipid deposition was significantly improved in the YCHD intervention group.Serum levels of TG,TC,AST,ALT and LDL-C were significantly de⁃creased.HOMA-IR and ISI were significantly reduced.The levels of uric acid,TG,IL-1β,IL-18 and XOD activity in the liver were significantly decreased.The protein expression of NLRP3,ASC,Caspase-1 and the mRNA expression levels of NLRP3,SREBP-1c,FASN in the liver were significantly decreased(P<0.05).Conclusion YCHD may regulate hepat

关 键 词：代谢相关脂肪性肝病 茵陈蒿汤 尿酸 NLRP3 胰岛素抵抗 甘油三酯 

分 类 号：R285.5[医药卫生—中药学]