广州医药 ›› 2025, Vol. 56 ›› Issue (5): 644-649.DOI: 10.20223/j.cnki.1000-8535.2025.05.010

• 论著 • 上一篇    下一篇

NXT629调控脂质代谢改善肝胆结石的机制研究

陈浩, 林梁, 邹来宾, 邱旭彬   

  1. 广州市花都区人民医院肝胆胰外科(广东广州 510800)
  • 收稿日期:2024-09-12 出版日期:2025-05-20 发布日期:2025-06-17
  • 基金资助:
    广州市花都区人民医院重点学科自拟科研项目(23ZDXKZN11);广州市花都区人民医院院内医学重点学科建设项目(消化病学科YNZDXK202201);广州市花都区人民医院院内基金项目(2021B02)

The mechanism of NXT629 regulating lipid metabolism to improve hepatolithiasis

CHEN Hao, LIN Liang, ZOU Laibin, QIU Xubin   

  1. Department of Hepatobiliary and Pancreatic Surgery,People’s Hospital of Huadu District,Guangzhou 510800,China
  • Received:2024-09-12 Online:2025-05-20 Published:2025-06-17

摘要: 目的 探讨NXT629改善肝胆结石形成的相关机制。方法 对C57BL/6J小鼠分别采用常规饮食或成石饮食(LD)喂养,并在LD组小鼠注射PPAR-α拮抗剂NXT629。通过苏木精-伊红染色法染色分析肝脂肪病变,油红O染色检测肝脏脂质的积累,分光光度法检测胆汁或血清中总胆固醇、甘油三酯、磷脂、总胆汁酸、胆固醇饱和指数、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇指标;qPCR法检测小鼠肝组织中ABCG5/8、CYP7A1、CYP7B1、PPAR-α和ABCB11 mRNA的表达情况。结果 NXT629通过靶向PPAR-α降低LD组小鼠肝脏中的ABCG5、ABCG8、ABCB11 mRNA水平以及增加CYP7A1、CYP7B1 mRNA水平,进而减少LD诱导的肝胆结石形成并改善脂质代谢紊乱。结论 NXT629可能通过影响脂代谢相关基因表达改善肝胆结石。

关键词: NXT629, 脂代谢, 肝胆结石, 成石饮食, PPAR-α

Abstract: Objective To explore the mechanism on NXT629 improves hepatolithiasis formation.Methods C57BL/6J mice were fed either a regular diet or a lithogenic diet(LD),with the LD group receiving injections of PPAR-α inhibitor NXT629.Liver steatosis was analyzed via HE staining,hepatic lipid accumulation was detected by Oil Red O staining,and total cholesterol,triglycerides,phospholipids,total bile acids,cholesterol saturation index,low density lipoprotein cholesterol,and high density lipoprotein cholesterol levels in bile or serum were measured using assay kits.RT-qPCR was employed to determine the mRNA expression of ABCG5/8,CYP7A1,CYP7B1,PPAR-α,and ABCB11 in mouse liver tissues.Results The Results showed that NXT629 target PPAR-α to down-regulate the mRNA levels of ABCG5,ABCG8,and ABCB11 in the livers of LD-fed mice,while increasing the mRNA levels of CYP7A1 and CYP7B1,thereby reducing LD-induced hepatolithiasis formation and improving lipid metabolism disorders.Conclusions NXT629 can improve cholesterol gallstones by affecting the expression of genes related to lipid metabolism.

Key words: NXT629, lipid metabolism, hepatolithiasis, lithogenic diet, PPAR-α