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米诺环素作为实验性2型糖尿病的心脏保护剂——一种具有心脏保护作用的抗菌药物。

Minocycline as heart conditioning agent in experimental type 2 diabetes mellitus - an antibacterial drug in heart protection.

作者信息

Sobot Nikola M, Sobot Tanja S, Jeremic Jovana N, Bolevich Sergey B, Bolevich Stefani S, Mitrovic Slobodanka Lj, Fisenko Vladimir P, Inic Sofija G, Samanovic Andjela D Milojevic, Rankovic Marina R, Srejovic Ivan M, Zivkovic Vladimir I, Jakovljevic Vladimir Lj

机构信息

Clinic for Cardiac Surgery, University Clinical Centre of the Republic of Srpska, Dvanaest beba st. bb, 78000, Banja Luka, Bosnia and Herzegovina.

Department of Physiology, University of Banja Luka, Save Mrkalja st. 14, 78000, Banja Luka, Bosnia and Herzegovina.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2022 Apr;395(4):429-444. doi: 10.1007/s00210-021-02179-y. Epub 2022 Feb 3.

DOI:10.1007/s00210-021-02179-y
PMID:35113200
Abstract

Cardiovascular diseases, and among them certainly myocardial infarction, remain leading cause of death worldwide. Diabetes increases risk of occurrence as well as adverse outcome of myocardial infarction. Conditioning maneuvers are the most attractive method for alleviating both the consequences of ischemia and reperfusion. Minocycline is a tetracycline derivative which exerts antioxidant, anti-inflammatory, and anti-apoptotic effects. The aim of this study was to assess the protective ability of preconditioning and postconditioning of isolated hearts from healthy and rats with experimentally induced type 2 diabetes with minocycline on functional recovery and redox status after ischemia and reperfusion. The hearts from healthy and diabetic rats were excised and retrogradely perfused according to the Langendorff technique. Using sensor in the left ventricle, the cardiodynamic parameters were recorded and in the samples of the coronary venous effluent oxidative stress biomarkers were analyzed. Minocycline was injected directly into the coronary vessels, in preconditioning 5 min before global ischemia, and in postconditioning during the first 5 min of reperfusion. Results of this study clearly show beneficial effects of minocycline applied both before ischemia and in the first minutes of reperfusion fashion in both healthy and diabetic rat hearts. The most prominent protective effect regarding oxidative stress is related to the decreased production of superoxide anion radical due postconditioning with minocycline in diabetic hearts. Cardiodynamic parameters were significantly improved in minocycline conditioned groups. Superoxide anion radical stands out as the most susceptible to changes induced by minocycline.

摘要

心血管疾病,其中肯定包括心肌梗死,仍然是全球主要的死亡原因。糖尿病会增加心肌梗死的发生风险以及不良后果。预处理措施是减轻缺血和再灌注后果最具吸引力的方法。米诺环素是一种四环素衍生物,具有抗氧化、抗炎和抗凋亡作用。本研究的目的是评估用米诺环素对健康大鼠和实验性诱导的2型糖尿病大鼠离体心脏进行预处理和后处理,对缺血再灌注后功能恢复和氧化还原状态的保护能力。将健康大鼠和糖尿病大鼠的心脏切除,按照Langendorff技术进行逆行灌注。使用左心室内的传感器记录心脏动力学参数,并分析冠状静脉流出液样本中的氧化应激生物标志物。米诺环素直接注入冠状血管,预处理在全心缺血前5分钟进行,后处理在再灌注的前5分钟进行。本研究结果清楚地表明,在健康大鼠和糖尿病大鼠心脏中,在缺血前和再灌注的最初几分钟应用米诺环素均有有益作用。关于氧化应激,最显著的保护作用与糖尿病心脏中米诺环素后处理导致超氧阴离子自由基产生减少有关。米诺环素预处理组的心脏动力学参数有显著改善。超氧阴离子自由基是最易受米诺环素诱导变化影响的物质。

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本文引用的文献

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Front Physiol. 2021 Feb 22;12:534127. doi: 10.3389/fphys.2021.534127. eCollection 2021.
2
Minocycline reduces inflammatory response and cell death in a S100B retina degeneration model.米诺环素可减少 S100B 视网膜变性模型中的炎症反应和细胞死亡。
J Neuroinflammation. 2020 Dec 14;17(1):375. doi: 10.1186/s12974-020-02012-y.
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Minocycline reverses IL-17A/TRAF3IP2-mediated p38 MAPK/NF-κB/iNOS/NO-dependent cardiomyocyte contractile depression and death.
神经病理性疼痛研究进展:选定的细胞内因子作为多向镇痛药的潜在靶点
Pharmaceuticals (Basel). 2023 Nov 17;16(11):1624. doi: 10.3390/ph16111624.
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Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning.心血管不可变风险因素、合并症和合并用药与缺血/再灌注损伤的相互作用,以及药物治疗和缺血预处理的心脏保护作用。
Pharmacol Rev. 2023 Jan;75(1):159-216. doi: 10.1124/pharmrev.121.000348. Epub 2022 Dec 8.
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Cell Signal. 2020 Sep;73:109690. doi: 10.1016/j.cellsig.2020.109690. Epub 2020 Jun 15.
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