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基于肠道菌群和代谢组学技术研究芍药苷抗高泌乳素血症的作用机制
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| 篇名： | 基于肠道菌群和代谢组学技术研究芍药苷抗高泌乳素血症的作用机制 |
| TITLE： | Mechanisms of paeoniflorin in treating hyperprolactinemia based on gut microbiota and metabolomics |
| 摘要： | 目的 探讨芍药苷抗高泌乳素血症（HPRL）的作用机制。方法将24只雌性SD大鼠分为空白对照组（灌胃5%阿拉伯胶溶液）、奥氮平组（模型组，灌胃5mg/kg奥氮平混悬液）、芍药苷组（灌胃5mg/kg奥氮平混悬液，2h后再灌胃50mg/kg芍药苷溶液），每组8只。每天1次，连续造模/给药至奥氮平组血浆泌乳素（PRL）水平高于空白对照组2倍。末次给药后，检测各组大鼠的血浆PRL水平，分析其肠道菌群变化[包括α多样性（Simpson、Chao1、Shannon指数）、β多样性和物种组成（门/属水平）分析、微生物组学LEfSe分析]；进行粪便非靶向代谢组学技术分析（包括多元统计分析、差异代谢物筛选及通路富集分析）；采用Spearman相关分析探究差异菌群与粪便差异代谢物的相关性。结果与奥氮平组比较，芍药苷组大鼠血浆PRL水平显著降低（P＜0.05）。16SrRNA高通量测序结果显示，芍药苷可显著改善HPRL大鼠肠道菌群的α多样性和β多样（P＜0.05），使其趋向于空白对照组。在门水平上，芍药苷可显著降低HPRL大鼠厚壁菌门、脱硫菌门的相对丰度，显著升高疣微菌门的相对丰度（P＜0.05）；在属水平上，芍药苷可显著逆转HPRL大鼠脱硫弧菌属、异杆菌属、普雷沃氏菌属NK3B31组等相对丰度的变化（P＜0.05）。LEfSe分析结果显示，芍药苷可显著富集放线菌门、葡萄球菌目、棒状杆菌目等菌群（P＜0.05）。共筛选出51个差异代谢物，代谢产物显著聚集于类固醇激素生物合成、前列腺癌、卵巢类固醇生成等代谢通路。相关性分析显示，肠道差异菌属如脱硫弧菌属、气球菌属等的相对丰度与四氢皮质醇、肾上腺甾酮等类固醇激素代谢物含量显著相关（P＜0.05）。结论芍药苷可能通过调节HPRL大鼠肠道菌群结构（包括显著降低脱硫弧菌属、异杆菌属、气球菌属的相对丰度，显著上调瘤胃球菌科UBA1819组、鼠肠杆菌属的相对丰度）、调控类固醇激素生物合成代谢通路来降低PRL水平，从而发挥抗HPRL的作用。 |
| ABSTRACT： | OBJECTIVE To investigate the mechanisms of paeoniflorin （PF） in anti-hyperprolactinemia （HPRL）. METHODS Twenty-four female SD rats were divided into blank control group （intragastric administration of 5% gum arabic solution）， olanzapine group （model group， intragastric administration of 5 mg/kg olanzapine suspension）， and PF group （intragastric administration of 5 mg/kg olanzapine suspension， followed by gavaging with 50 mg/kg PF solution 2 hours later） with 8 rats in each group. Once a day， continuously model/administer until the plasma prolactin （PRL） levels in the olanzapine group were twice as high as those in the blank control group. PRL levels were measured. The changes in gut microbiota of rats were analyzed， including assessments of α-diversity （Simpson， Chao1， and Shannon indexes）， β-diversity， species composition analysis （at the phylum and genus levels）， and microbiome LEfSe analysis. Fecal untargeted metabolomics technology was employed to analyze the effects of PF on the fecal metabolomics of rats， including multivariate statistical analysis， screening of differential metabolites， and pathway enrichment analysis. Spearman correlation analysis was performed to examine the correlations between differential microbiota and differential fecal metabolites. RESULTS PF significantly reduced serum PRL levels of rats in olanzapine group （P＜0.05）. 16S rRNA sequencing revealed that PF improved the α-diversity and β-diversity of gut microbiota in HPRL rats （P＜0.05）， restoring them to levels similar to the blank control group. At the phylum level， PF significantly reduced the relative abundance of Firmicutes and Desulfobacterota， while increasing the relative abundance of Verrucomicrobiota in HPRL rats （all P＜0.05）. At the genus level， PF reversed the relative abundance of Desulfovibrio，Allobaculum， and Prevotellaceae_NK3B31_group， etc （all P＜0.05）. The results of LEfSe analysis revealed that PF significantly enriched microbial taxa such as Actinobacteriota，Staphylococcales， Corynebacteriales， etc （all P＜0.05）. Metabolomics analysis identified 51 differential metabolites， with key metabolic pathways enriched in steroid hormone biosynthesis， prostate cancer， ovarian steroidogenesis， etc. Correlation analysis showed that the relative abundance of gut microbiota such as Desulfovibrio and Aerococcus was significantly correlated with the levels of steroid hormone metabolites such as tetrahydrocortisol and adrenosterone （P＜0.05）. CONCLUSIONS PF alleviates PRL by modulating gut microbiota structure in HPRL rats （including significantly reducing the relative abundance of Desulfovibrio， Allobaculum and Aerococcus， as well as significantly increasing the relative abundance of Ruminococcaceae_UBA1819 and Muribaculum）， and regulating steroid hormone pathways， then exerting its anti-HPRL effect. |
| 期刊： | 2025年第36卷第13期 |
| 作者： | 林冰淇；魏媛怡；易云；王春霞 |
| AUTHORS： | LIN Bingqi，WEI Yuanyi，YI Yun，WANG Chunxia |
| 关键字： | 芍药苷；高泌乳素血症；代谢组学；肠道菌群；泌乳素；差异代谢物 |
| KEYWORDS： | paeoniflorin； hyperprolactinemia； metabolomics； gut microbiota； prolactin； differential meta-bolites |
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