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Archive > Volume 16 Issue 1 > 2024,16(1):121-131. DOI:https://doi.org/10.1016/j.chmed.2023.10.002 Prev Next

基于藥代動力學(xué)及代謝組學(xué)探討大黃和土鱉蟲 對肝臟保護(hù)機(jī)制的影響

Original articles

Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics

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    摘要:
    目的 基于高效液相色譜/質(zhì)譜聯(lián)用（HPLC-MS/MS）及核磁共振氫譜（1H-NMR）代謝組學(xué)技術(shù)，探索在急性肝損傷病理狀態(tài)下大黃蟄蟲丸（DHZCP）中大黃以及土鱉蟲配伍（RhRR-EuS）大黃（RhRR）時的藥物代謝動力學(xué)特征及治療機(jī)制。 方法 建立急性肝損傷模型，利用HPLC-MS/MS建立DHZCP君藥中5種成分的藥物代謝動力學(xué)研究方法。采用1H-NMR結(jié)合多元統(tǒng)計分析方法對不同組別小鼠的肝組織進(jìn)行分析，以研究RhRR-EuS和RhRR的代謝組學(xué)。 結(jié)果 藥物代謝動力學(xué)結(jié)果顯示，不同組別中存在不同程度的雙峰現(xiàn)象，而與土鱉蟲配伍后大黃中的游離蒽醌吸收增加。此外，大鼠急性肝損傷的病理狀態(tài)可選擇性地促進(jìn)大黃素、大黃酚、大黃素甲醚和蘆薈大黃素的吸收。通過急性肝損傷小鼠肝組織中的15種差異代謝物，揭示了RhRR-EuS和RhRR可通過調(diào)節(jié)谷氨酰胺和谷氨酸代謝、丙氨酸、天冬氨酸和谷氨酸代謝、磷酸肌醇代謝來保護(hù)肝損傷。而RhRR的調(diào)節(jié)作用弱于RhRR-EuS。 結(jié)論 我們首次研究急性肝損傷大鼠和小鼠體內(nèi)RhRR-EuS和RhRR的藥代動力學(xué)及代謝組學(xué)差異，以期為DHZCP臨床治療肝病提供理論參考。

    Abstract:
    Objective: Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (1H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored. Methods: Models of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by 1H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR. Results: Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS. Conclusion: For the first time, we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

    關(guān)鍵詞:
    土鱉蟲;大黃蟄蟲丸;1H-NMR;HPLC-MS/MS;代謝組學(xué);藥物代謝動力學(xué);大黃

    Keywords:


    Project Supported:
    This work was supported by the Key R&D Plan of Hubei Province for local special support in the field of general health (No. 2022BCE066).

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