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。

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．

       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。

       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．