Radix Angelica dahuricae extract ameliorates oestrogen deficiency-induced dyslipidaemia in ovariectomized (OVX) rats by modulating the gut microbiota and bile acid signalling
Radix Angelica dahuricae extract ameliorates oestrogen deficiency-induced dyslipidaemia in ovariectomized (OVX) rats by modulating the gut microbiota and bile acid signalling
复制标题
白芷提取物通过调节肠道微生物群和胆汁酸信号改善卵巢切除 (OVX) 大鼠雌激素缺乏引起的血脂异常
DOI：
10.1016/j.phymed.2022.154440
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发表时间：
2022-09-24
期刊：
影响因子：
7.9
通讯作者：
Li, Min
中科院分区：
文献类型：
--
作者：
Chen, Lin;Liu, Yanru;Li, Min
背景：白芷（Angelica dahuricae， RAD）是一种著名的中药，具有缓解脂质代谢的作用。然而，RAD对雌激素缺乏引起的血脂异常的改善作用及其机制尚不清楚。目的：研究RAD对卵巢切除（OVX）大鼠雌激素缺乏引起的血脂异常的影响，并探讨肠道菌群和胆汁酸信号在保护作用中的作用。方法：采用双侧卵巢切除术建立雌激素缺乏模型。检测血清生化指标、肝脏脂质、炎症因子及组织形态学。通过16S rRNA测序分析肠道微生物。采用气相色谱-火焰电离检测法（GC-FID）和超高效色谱-串联质谱法（UPLC-MS/MS）分别定量测定粪便短链脂肪酸（SCFAs）和血清胆汁酸。实时荧光定量PCR检测肝脏和盲肠中胆汁酸合成、代谢和肠肝循环相关基因的表达。结果：RAD给药能显著降低OVX大鼠的体重、血清和肝脏中TC和TG水平，并能显著降低肝脏脂肪变性和炎症。RAD可以显著调节OVX大鼠肠道微生物组成，增加乳酸杆菌的丰度，增加胆汁盐水解酶（BSH）的含量，重建SCFA谱和胆汁酸代谢谱。RAD可增加HMG-CoA还原酶（HMGCR）和细胞色素P450 7A1 （CYP7A1）基因表达，调节相关受体基因表达及肠肝循环蛋白表达。结论：RAD可减轻雌激素缺乏引起的OVX大鼠血脂异常。肠道菌群组成和胆汁酸信号的调节可能是潜在的机制。
Background: Radix Angelica dahuricae (RAD), a well-known traditional Chinese medicine, displays a promising effect on alleviating lipid metabolism. However, the improvement of RAD on oestrogen deficiency-induced dyslipidaemia and the underlying mechanism are unclear.Purpose: The aim of this study was to study the effect of RAD on oestrogen deficiency-induced dyslipidaemia in ovariectomized (OVX) rats and investigate the involvement of the gut microbiota and bile acid signalling in the protective effects.Methods: Bilateral ovariectomy was executed to establish an oestrogen deficiency model. Serum biochemical indexes, liver lipids, inflammatory cytokines and histomorphology were evaluated. Gut microbes were analysed via 16S rRNA sequencing. Faecal short-chain fatty acids (SCFAs) and serum bile acids were quantified by gas chromatography-flame ionization detection (GC-FID) and ultra-high-performance chromatography-tandem mass spectrometry (UPLC-MS/MS), respectively. The expression of genes related to bile acid synthesis, metabolism and enterohepatic circulation in the liver and caecum was measured by real-time PCR.Results: The results displayed that RAD administration markedly decreased body weight, TC and TG levels in the serum and liver, and hepatic steatosis and inflammation in OVX rats. RAD administration could significantly regulate the gut microbial composition, increasing the abundance of Lactobacillus, increasing the content of bile salt hydrolase (BSH), and reestablishing the SCFA profile and bile acid metabolism profile in OVX rats. RAD administration could increase the gene expression of HMG-CoA reductase (HMGCR) and cytochrome P450 7A1 (CYP7A1) and regulate the gene expression of the related receptors as well as proteins in enterohepatic circulation.Conclusions: RAD alleviated oestrogen deficiency-induced dyslipidaemia in OVX rats. Modulation of the gut microbiota composition and bile acid signalling may be the underlying mechanism.