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Archive > Volume 16 Issue 4 > 2024,16(4):612-621. DOI:https://doi.org/10.1016/j.chmed.2023.12.003 Prev Next

從多組學(xué)角度解讀抑郁癥與微生物分子的關(guān)系——以柴歸顆粒為例

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Deciphering relationship between depression and microbial molecules based on multi-omics: A case study of Chaigui Granules

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    摘要:
    目的：從抑郁癥與微生物分子的關(guān)系入手，從多組學(xué)角度解讀柴歸顆粒的抗抑郁作用。 方法：雄性SD大鼠接受7周慢性不可預(yù)測(cè)輕度應(yīng)激（CUMS），并在后4周進(jìn)行抗抑郁藥柴歸顆粒提取物和柴歸顆粒治療。采用行為學(xué)測(cè)試和單胺類(lèi)神經(jīng)遞質(zhì)含量測(cè)定對(duì)柴歸顆粒進(jìn)行藥效學(xué)評(píng)價(jià)。采用16S rRNA測(cè)序、LC-MS技術(shù)和分子生物學(xué)技術(shù)，探討柴歸顆粒的藥理作用機(jī)制。 結(jié)果：柴歸顆粒呈劑量依賴(lài)性地減輕CUMS大鼠抑郁行為指標(biāo)，調(diào)節(jié)單胺類(lèi)神經(jīng)遞質(zhì)含量。柴歸顆粒還可以改善空腸腸道微生物群的精氨酸代謝紊亂。同時(shí)，血清和海馬中精氨酸及其代謝產(chǎn)物的含量被調(diào)節(jié)至正常水平。進(jìn)一步的研究表明，通過(guò)qRT-PCR和Western blotting驗(yàn)證了柴歸顆?？梢哉{(diào)節(jié)相關(guān)限速酶基因和蛋白在海馬中的表達(dá)。結(jié)果表明，柴歸顆粒對(duì)腸道微生物群、代謝產(chǎn)物以及參與精氨酸途徑的限速酶的基因和蛋白質(zhì)進(jìn)行了顯著調(diào)節(jié)。 結(jié)論：柴歸顆?？赡芡ㄟ^(guò)調(diào)節(jié)精氨酸代謝發(fā)揮抗抑郁作用，其機(jī)制可能與調(diào)節(jié)腸道微生物群和相關(guān)代謝酶有關(guān)。

    Abstract:
    Objective: To decipher the antidepression effect of Chaigui Granules (CGKL) from the relationship between depression and microbial molecules based on multi-omics. Methods: Male SD rats were subjected to chronic unpredictable mild stress (CUMS) for seven weeks. The antidepressants CGKL extract and CGKL were administered for the following four weeks. The behavior test and the content of monoamine neurotransmitters were used to evaluate the efficacy of CGKL. The 16S rRNA sequencing, LC-MS technology and molecular biological techniques were used to explore the pharmacological mechanism of CGKL. Results: CGKL treatment obviously alleviated the depressive behavioral indicators and regulated the content of monoamine neurotransmitters, and presented dose-dependent manner. CGKL could also improve the arginine metabolism disorder of gut microbiota in the jejunum. Meanwhile, the contents of arginine and its metabolites in the serum and hippocampus were regulated to normal levels. Further investigation indicated that the expression of related rate-limiting enzyme genes and proteins in the hippocampus was validated by qRT-PCR and Western blotting. The results showed that the gut microbiota, metabolites, and genes or proteins of rate-limiting enzymes involved in the arginine pathway were significantly regulated by CGKL. Conclusion: The present study demonstrates that CGKL might exert antidepressant effects through regulating arginine metabolism, and its mechanism may be related to modulating the gut microbiota and related metabolic enzyme.

    關(guān)鍵詞:
    精氨酸代謝，柴歸顆粒，抑郁癥，腸道菌群，微生物分子

    Keywords:


    Project Supported:
    This work was supported by the National Natural Science Foundation of China (No. 82074147, 82374153); the Science and Technology of Shanxi Province (No. 202103021224026); and the Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province (No. 202105D121009).

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