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心脏移植术后患者排斥反应发展过程中的辅酶Q10耗竭与线粒体能量紊乱

Coenzyme Q10 depletion and mitochondrial energy disturbances in rejection development in patients after heart transplantation.

作者信息

Gvozdjáková A, Kucharská J, Mizera S, Braunová Z, Schreinerová Z, Schrameková E, Pechán I, Fabián J

机构信息

Pharmacobiochemical Laboratory of Medical Faculty, Comenius University, Bratislava, Slovak Republic.

出版信息

Biofactors. 1999;9(2-4):301-6. doi: 10.1002/biof.5520090227.

Abstract

UNLABELLED

Sixty endomyocardial biopsies (EMB) and whole blood or plasma samples from 34 patients after heart transplantation (HTx-pts) were studied. Acute rejection of the transplanted heart was histologically graded as: 0 (without), 0-1 (incipient), 1 (mild), 2 (moderate). The level of coenzyme Q10 (CoQ10) in 28 EMB was estimated by HPLC. Mitochondrial respiratory chain function and energy production were measured in 60 EMB. This study is the first report showing a correlation between: (a) histological signs of rejection in the human transplanted heart and (b) CoQ10 level of EMB, CoQ10 blood level, and mitochondrial bioenergetic processes: inhibition in FAD-part, but not in NAD-part of respiratory chain. In all patients after heart transplantation (HTx-pts) the dynamic balance between total antioxidant status and degree of oxidative stress was disturbed.

CONCLUSIONS

CoQ10 level and mitochondrial bioenergetic functions of EMB contribute to the explanation of pathobiochemical mechanisms of origin and development rejection of human transplanted heart. We suppose that estimation of EMB CoQ10 level could be used as a bioenergetic marker of rejection development in human transplanted heart. CoQ10 therapy could contribute to the prevention of rejection of the transplanted heart.

摘要

未标注

对60份心内膜心肌活检样本(EMB)以及34例心脏移植患者(HTx患者)的全血或血浆样本进行了研究。移植心脏的急性排斥反应在组织学上分级为:0级(无)、0 - 1级(初期)、1级(轻度)、2级(中度)。通过高效液相色谱法(HPLC)测定了28份EMB样本中辅酶Q10(CoQ10)的水平。在60份EMB样本中测量了线粒体呼吸链功能和能量产生。本研究首次报告了以下两者之间的相关性:(a)人类移植心脏排斥反应的组织学迹象与(b)EMB的CoQ10水平、血液CoQ10水平以及线粒体生物能量过程:呼吸链的黄素腺嘌呤二核苷酸(FAD)部分受到抑制,但烟酰胺腺嘌呤二核苷酸(NAD)部分未受抑制。在所有心脏移植患者(HTx患者)中,总抗氧化状态与氧化应激程度之间的动态平衡受到干扰。

结论

EMB的CoQ10水平和线粒体生物能量功能有助于解释人类移植心脏排斥反应发生和发展的病理生化机制。我们认为,测定EMB的CoQ10水平可作为人类移植心脏排斥反应发展的生物能量标志物。CoQ10治疗可能有助于预防移植心脏的排斥反应。

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