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研究探讨了氢化镁对阿托伐他汀降血脂作用的增强效果:体内和体外研究。

The augment effects of magnesium hydride on the lipid lowering effect of atorvastatin: an in vivo and in vitro investigation.

机构信息

School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Department of Naval Medicine, Naval Medical University, Shanghai, China.

出版信息

Med Gas Res. 2025 Mar 1;15(1):148-155. doi: 10.4103/mgr.MEDGASRES-D-23-00047. Epub 2024 Jul 25.

Abstract

There is strong evidence connecting increased serum lipid levels to cardiovascular disorders, including atherosclerosis. Statins is prescribed as the primary medication to decrease lipid levels. Recent research has demonstrated that hydrogen possesses anti-inflammatory and antioxidant properties by modulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, ultimately leading to the preservation of lipid homeostasis. Magnesium hydride (MgH2) is a prolonged stable hydrogen storage medium, which can be utilized to investigate its synergistic lipid-lowering effect with statins and its detailed molecular mechanism, both in vivo and in vitro. To ascertain the safety and efficacy of MgH2, we executed a comprehensive research of its influence on both physiological and pathological metrics. We noted a substantial diminution in lipid levels when MgH2 was integrated with atorvastatin, as attested by oil red staining. Furthermore, we scrutinized the regulatory effect of MgH2 on cytochrome P450 3A, which is a metabolic enzyme of statins, and discovered that it could be reduced by the MgH2. Concluding from our results, we propose that MgH2 inhibits the expression of cytochrome P450 3A in the liver and exerts an auxiliary lipid-lowering effect by increasing the blood concentration of statins. By augmenting our comprehension of MgH2's role in ameliorating lipid metabolism, we aspire to develop more promising therapies in the future.

摘要

有强有力的证据表明血清脂质水平的升高与心血管疾病有关,包括动脉粥样硬化。他汀类药物被开处方作为降低脂质水平的主要药物。最近的研究表明,氢气通过调节过氧化物酶体增殖物激活受体γ共激活因子-1α的表达具有抗炎和抗氧化特性,最终导致脂质稳态的维持。氢化镁(MgH2)是一种稳定的长效储氢介质,可用于研究其与他汀类药物的协同降血脂作用及其详细的分子机制,包括体内和体外。为了确定 MgH2 的安全性和有效性,我们全面研究了它对生理和病理指标的影响。我们注意到,当 MgH2 与阿托伐他汀联合使用时,脂质水平显著降低,油红染色证实了这一点。此外,我们研究了 MgH2 对细胞色素 P450 3A 的调节作用,细胞色素 P450 3A 是他汀类药物的代谢酶,发现它可以被 MgH2 降低。根据我们的结果,我们提出 MgH2 通过抑制肝脏中细胞色素 P450 3A 的表达,并通过增加他汀类药物的血液浓度来发挥辅助降血脂作用。通过加深我们对 MgH2 在改善脂质代谢中的作用的理解,我们希望在未来开发出更有前途的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a767/11515074/8e69649d1c37/MGR-15-148-g001.jpg

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