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Archive > Volume 17 Issue 3 > 2025,17(3):529-538. DOI:https://doi.org/10.1016/j.chmed.2025.04.009 Prev Next

黃連對(duì)高脂飲食引起的寒熱證小鼠的高脂血癥和腸道菌群有明顯的影響

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Coptis chinensis shows distinct effects on hyperlipidemia and gut microbiota in high-fat diet induced mice with cold or hot syndrome

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    摘要:
    目的：黃連（簡(jiǎn)稱“HL”）在臨床應(yīng)用中常被用于治療熱證患者的血脂異常。其降脂效果在高脂肪飲食（HFD）誘導(dǎo)的高脂血癥動(dòng)物模型中已得到證實(shí)。然而，HL在 HFD 飲食的熱證或寒證動(dòng)物中的效果是否存在差異尚不清楚。本研究旨在探究 HL 在 HFD 飲食的熱證或寒證小鼠中抗高脂血癥效果的差異。 方法：通過兩周的冰水（0°C）和左甲狀腺素鈉（240 毫克/千克）治療，將 HFD 誘導(dǎo)的 C57BL/6 小鼠分別置于冷證或熱證狀態(tài)。隨后，在接下來的四周內(nèi)，通過口服灌胃給小鼠給予 HL 的水提取物。測(cè)定血清和肝臟中的脂質(zhì)水平，以確定 HL 的降脂效果。此外，使用全長(zhǎng) 16S rRNA 基因測(cè)序來闡明腸道微生物群的組成。 結(jié)果：HL 顯著降低了 HFD 誘導(dǎo)的高脂血癥小鼠的脂質(zhì)水平。其效果在熱證的高脂血癥小鼠中增強(qiáng)，但在寒證的小鼠中顯著減弱。HL 治療導(dǎo)致兩組小鼠的腸道微生物群的α多樣性（以 ACE、Chao1、Shannon 和 Simpson 指數(shù)來衡量）均有所下降，但根據(jù)病癥的不同，它還影響了特定的微生物群體。具體而言，盡管 HL 導(dǎo)致 Eubacterium、Robinsoniella 和 Lachnoclostridium 族的顯著增加，以及在所有條件下 Clostridium innocuum 和 Bacteroides thetaiotaomicron 物種的增強(qiáng)，但它根據(jù)熱癥的類型有針對(duì)性地刺激了熱癥小鼠中的 Romboutsia ilealis 和 Parabaceroides_sp_HGS0025 物種。 結(jié)論：HL 對(duì)患有熱癥的高血脂小鼠具有更強(qiáng)的降脂效果，這與它在臨床上的傳統(tǒng)用途相符。HL 的治療效果至少在一定程度上與它對(duì)腸道微生物群的調(diào)節(jié)作用有關(guān)，為傳統(tǒng)中醫(yī)的基礎(chǔ)原理提供了新的見解。

    Abstract:
    Objective: Coptis chinensis (Huanglian in Chinese, HL) is commonly utilized in clinical settings to counteract dyslipidemia in patients with hot syndrome. Its lipid-reducing efficacy has been consistently demonstrated in high-fat diet (HFD)-induced hyperlipidemic animal models. However, whether HL’s efficacy differs in HFD-fed animals with hot or cold syndromes remains unclear. This study aims to discern the variations in the anti-hyperlipidemic effects of HL in HFD-fed mice with hot or cold syndromes. Methods: HFD-induced C57BL/6 mice were subjected to cold or hot syndrome via two weeks of ice water (0 °C) and levothyroxine sodium (240 lg/kg) treatment, respectively. Then, an aqueous extract of HL was administered to the mice via oral gavage over the following four-week period. Lipid levels in the serum and liver were gauged to determine the lipid-reducing effects of HL. Furthermore, gut microbiota composition was elucidated using full-length 16S rRNA gene sequencing. Results: HL notably reduced lipid levels in HFD-induced hyperlipidemic mice. Its efficacy was amplified in hyperlipidemic mice with a hot syndrome but was markedly reduced in those with a cold syndrome. HL treatment led to a decline in alpha-diversity (characterized by ACE, Chao1, Shannon and Simpson index) of the gut microbiota in both sets of mice but affected specific microbial populations based on the syndrome. Specifically, while HL led to a notable increase in Eubacterium, Robinsoniella, and Lachnoclostridium genera, along with the enhancement of Clostridium innocuum and Bacteroides thetaiotaomicron species across all conditions, it syndrome-dependently stimulated Romboutsia ilealis and Parabaceroides_sp_HGS0025 species in mice with hot syndrome. Conclusion: HL shows stronger lipid-lowering effect on hyperlipidemic mice with hot syndrome, which is in accordance with its traditional usage in clinic. The therapeutic outcomes of HL are intrinsically tied, at least in part, to its modulatory effects on the gut microbiota, offering fresh insights into the foundational principles of traditional Chinese medicine.

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    Project Supported:
    This work was supported financially by the National Natural Science Foundation of China (No. 81973217).

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