| 徐心仪,郑妍,方珍珍,等.基于血清代谢组学研究祛浊通痹方改善高脂饮食诱导的肥胖小鼠胆汁酸代谢紊乱[J].浙江中医药大学学报,2024,48(10):1191-1198. |
| 基于血清代谢组学研究祛浊通痹方改善高脂饮食诱导的肥胖小鼠胆汁酸代谢紊乱 |
| Study on the Mechanism of Quzhuo Tongbi Formula Relieving Bile Acid Metabolism Disorder Induced by High Fat Diet in Mice Based on Serum Metabolomics |
| DOI：10.16466/j.issn1005-5509.2024.10.001 |
| 中文关键词: 高脂血症 血清代谢组学 祛浊通痹方 生物标志物 FXR-SHP 胆汁酸代谢 超高效液相色谱-四极杆飞行时间串联质谱 靶点验证 |
| 英文关键词: hyperlipidemia serum metabolomics Quzhuo Tongbi Formula biomarkers FXR-SHP bile acid metabolism ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry target validation |
| 基金项目:国家重点研发计划项目(2022YFC3501204)；浙江中医药大学国基预研专项(2023GJYY09) |
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| 中文摘要: |
| [目的] 基于血清代谢组学探究祛浊通痹方(Quzhuo Tongbi，QZTB)改善高脂饮食(high fat diet，HFD)诱导的肥胖小鼠胆汁酸代谢紊乱的相关机制。[方法] 将雄性C57BL/6J小鼠随机分为空白组、HFD模型组和QZTB组，采用超高效液相色谱-四极杆飞行时间串联质谱(ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry，UHPLC-QTOF-MS)技术进行血清代谢组学分析，筛选潜在生物标志物。通过实时荧光定量聚合酶链式反应(Real-time quantitative polymerase chain reaction，RT-qPCR)验证富集代谢通路的关键靶点。[结果] 代谢组学分析共筛选到 103个潜在生物标志物，主要富集到胆汁酸生物合成代谢通路，提示QZTB可明显改善HFD诱导的小鼠胆汁酸代谢紊乱。RT-qPCR结果显示，与空白组比较，HFD模型组小鼠肝组织胆固醇7α羟化酶(cholesterol 7-alpha hydroxylase，CYP7A1)、细胞色素P450家族8亚家族B成员1(cytochrome P450 family 8 subfamily B member 1，CYP8B1)、法尼醇X受体(farnesoid X receptor，FXR)及小异源二聚体(small heterodimer partner，SHP)表达量显著降低(P<0.01，P<0.01，P<0.001，P<0.01)；经QZTB干预后经典途径关键酶CYP7A1与CYP8B1明显升高(P<0.01，P<0.05)，FXR与SHP被激活(P<0.05)，固醇调节元件结合蛋白-1C(sterol regulatory elementbinding protein-1C，SREBP-1C)和脂肪酸合成酶(fatty acidsynthase，FAS)被显著抑制(P<0.01，P<0.001)。[结论] QZTB主要通过提高胆汁酸合成经典途径关键酶的活性，促进初级胆汁酸的合成，激活FXR-SHP通路，调节胆汁酸生物合成代谢途径，从而改善HFD诱导的肥胖小鼠胆汁酸代谢紊乱。 |
| 英文摘要: |
| [Objective] To study the mechanism of Quzhuo Tongbi Formula(QZTB) in improving bile acid metabolism disorder induced by high fat diet(HFD) in mice using serum metabolomics. [Methods] Male C57BL/6J mice were randomly divided into blank， HFD model and QZTB groups. Serum metabolomic analysis was performed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS) technique to screen potential biomarkers. The key targets on the enriched pathway were verified using Real-time quantitative polymerase chain reaction(RT-qPCR) method. [Results] A total of 103 potential biomarkers were screened using serum metabolomics analysis， mainly enriched in bile acid bioanabolic pathway. QZTB treatment could significantly improve the bile acid metabolism disorder induced by HFD in mice. RT-qPCR results showed that compared with blank group， the expression levels of cholesterol 7-alpha hydroxylase(CYP7A1) and cytochrome P450 family 8 subfamily B member 1(CYP8B1) in liver tissue of HFD model group were inhibited(P<0.01)， and the expressions of farnitol X receptor(FXR) and small heterodimeric partner(SHP) also decreased(P<0.01， P<0.01， P<0.001， P<0.01). After QZTB treatment， the levels of key enzymes such as CYP7A1 and CYP8B1 on the classical pathway increased(P<0.01， P<0.05). FXR-SHP pathway was activated(P<0.05)， thereby sterol regulatory element binding protein-1C(SREBP-1C) and fatty acid synthase(FAS) were inhibited(P<0.01， P<0.001). [Conclusion] QZTB could improve bile acid metabolism disorder induced by HFD in obese mice， which be attributed to increasing the activity of key enzymes in the classical bile acid synthase，promoting the synthesis of primary bile acid， activating FXR-SHP pathway， and further regulating bile acid biosynthesis metabolism. |
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