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NXT629调控脂质代谢改善肝胆结石的机制研究

The mechanism of NXT629 regulating lipid metabolism to improve hepatolithiasis

来源期刊: 广州医药 | 644-649 发布时间:2025-06-17 收稿时间:2025/11/13 18:53:40 阅读量:61
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关键词:
NXT629脂代谢肝胆结石成石饮食PPAR-α
NXT629lipid metabolismhepatolithiasislithogenic dietPPAR-α
DOI:
10.20223/j.cnki.1000-8535.2025.05.010
收稿时间:
2024-09-12 
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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.
1、 ZHONG J,HE X,GAO X,et al.Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling[J].Nat Commun,2023,14(1):5451. ZHONG J,HE X,GAO X,et al.Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling[J].Nat Commun,2023,14(1):5451.
2、 ZHANG L,LI Y,WANG Y,et al.mTORC2 facilitates liver regeneration through sphingolipid-induced PPAR-α-fatty acid oxidation[J].Cell Mol Gastroenterol Hepatol,2022,14(6):1311-1331. ZHANG L,LI Y,WANG Y,et al.mTORC2 facilitates liver regeneration through sphingolipid-induced PPAR-α-fatty acid oxidation[J].Cell Mol Gastroenterol Hepatol,2022,14(6):1311-1331.
3、 YANG W,LING X,HE S,et al.PPARα/ACOX1 as a novel target for hepatic lipid metabolism disorders induced by per- and polyfluoroalkyl substances:An integrated approach[J].Environ Int,2023,178:108138. YANG W,LING X,HE S,et al.PPARα/ACOX1 as a novel target for hepatic lipid metabolism disorders induced by per- and polyfluoroalkyl substances:An integrated approach[J].Environ Int,2023,178:108138.
4、 ZHANG F M,JIANG X,LI S,et al.Simplified calculation of bile cholesterol saturation index[J].Hepatobiliary Pancreat Dis Int,2022,21(3):293-294. ZHANG F M,JIANG X,LI S,et al.Simplified calculation of bile cholesterol saturation index[J].Hepatobiliary Pancreat Dis Int,2022,21(3):293-294.
5、 XIA Y,XU Y,LIU Q,et al.Glutaredoxin 1 regulates cholesterol metabolism and gallstone formation by influencing protein S-glutathionylation[J].Metabolism,2023(145):155610. XIA Y,XU Y,LIU Q,et al.Glutaredoxin 1 regulates cholesterol metabolism and gallstone formation by influencing protein S-glutathionylation[J].Metabolism,2023(145):155610.
6、 ALMOHAWES Z N,EL-KOTT A,MORSY K,et al.Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats[J].Arch Physiol Biochem,2024,130(3):257-274. ALMOHAWES Z N,EL-KOTT A,MORSY K,et al.Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats[J].Arch Physiol Biochem,2024,130(3):257-274.
7、 CHEN Z,SHAO W,LI Y,et al.Inhibition of PCSK9 prevents and alleviates cholesterol gallstones through PPARα-mediated CYP7A1 activation[J].Metabolism,2024(152):155774. CHEN Z,SHAO W,LI Y,et al.Inhibition of PCSK9 prevents and alleviates cholesterol gallstones through PPARα-mediated CYP7A1 activation[J].Metabolism,2024(152):155774.
8、 GALLUCCI G M,HAYES C M,BOYER J L,et al.PPAR-mediated bile acid glucuronidation:Therapeutic targets for the treatment of cholestatic liver diseases[J].Cells,2024,13(15):1296. GALLUCCI G M,HAYES C M,BOYER J L,et al.PPAR-mediated bile acid glucuronidation:Therapeutic targets for the treatment of cholestatic liver diseases[J].Cells,2024,13(15):1296.
9、 FAN N,MENG K,ZHANG Y,et al.The effect of ursodeoxycholic acid on the relative expression of the lipid metabolism genes in mouse cholesterol gallstone models[J].Lipids Health Dis,2020,19(1):158. FAN N,MENG K,ZHANG Y,et al.The effect of ursodeoxycholic acid on the relative expression of the lipid metabolism genes in mouse cholesterol gallstone models[J].Lipids Health Dis,2020,19(1):158.
10、 CHOI Y J,YANG H S,ZHANG Y,et al.Intratracheal exposure to polyhexamethylene guanidine phosphate disrupts coordinate regulation of FXR-SHP-mediated cholesterol and bile acid homeostasis in mouse liver[J].Ecotoxicol Environ Saf,2022(247):114213. CHOI Y J,YANG H S,ZHANG Y,et al.Intratracheal exposure to polyhexamethylene guanidine phosphate disrupts coordinate regulation of FXR-SHP-mediated cholesterol and bile acid homeostasis in mouse liver[J].Ecotoxicol Environ Saf,2022(247):114213.
11、 YE X,SHEN S,XU Z,et al.Sodium butyrate alleviates cholesterol gallstones by regulating bile acid metabolism[J].Eur J Pharmacol,2021(908):174341. YE X,SHEN S,XU Z,et al.Sodium butyrate alleviates cholesterol gallstones by regulating bile acid metabolism[J].Eur J Pharmacol,2021(908):174341.
12、 FARHAT D,REZAEI F,RISTOVSKI M,et al.Structural analysis of cholesterol binding and sterol selectivity by ABCG5/G8[J].J Mol Biol,2022,434(20):167795. FARHAT D,REZAEI F,RISTOVSKI M,et al.Structural analysis of cholesterol binding and sterol selectivity by ABCG5/G8[J].J Mol Biol,2022,434(20):167795.
13、 SHARMA B,SHARMA S R.Evaluation of gallstone classification and their diagnosis through serum parameters as emerging tools in treatment:A narrative review[J].Postgrad Med,2022,134(7):644-653. SHARMA B,SHARMA S R.Evaluation of gallstone classification and their diagnosis through serum parameters as emerging tools in treatment:A narrative review[J].Postgrad Med,2022,134(7):644-653.
14、 JIN C G,JIANG F R,ZHANG J,et al.Role of osteopontin in diet-induced brown gallstone formation in rats[J].Chin Med J,2021,134(9):1093-1100. JIN C G,JIANG F R,ZHANG J,et al.Role of osteopontin in diet-induced brown gallstone formation in rats[J].Chin Med J,2021,134(9):1093-1100.
15、 SUN H,WARREN J,YIP J,et al.Factors influencing gallstone formation:A review of the literature[J].Biomolecules,2022,12(4):550. SUN H,WARREN J,YIP J,et al.Factors influencing gallstone formation:A review of the literature[J].Biomolecules,2022,12(4):550.
16、 ZHANG C,DAI W,YANG S,et al.Resistance to Cholesterol Gallstone Disease:Hepatic Cholesterol Metabolism[J].J Clin Endocrinol Metab,2024,109(4):912-923. ZHANG C,DAI W,YANG S,et al.Resistance to Cholesterol Gallstone Disease:Hepatic Cholesterol Metabolism[J].J Clin Endocrinol Metab,2024,109(4):912-923.
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