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瘦素与原发性高血压患者红细胞膜流动性:一项电子顺磁共振研究

Leptin and membrane fluidity of erythrocytes in essential hypertension. An electron paramagnetic resonance investigation.

作者信息

Tsuda Kazushi, Nishio Ichiro

机构信息

Division of Cardiology, Department of Medicine, Wakayama Medical University, Wakayama, Japan.

出版信息

Am J Hypertens. 2004 Apr;17(4):375-9. doi: 10.1016/j.amjhyper.2003.12.005.

Abstract

There has been an indication that leptin, the product of the human obesity gene, actively participates not only in metabolic regulation but also in the control of blood pressure. Recently, it has been proposed that abnormalities in the physical property of cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. We have shown previously that leptin significantly increased the membrane fluidity and improved the microviscosity of erythrocytes in humans through the nitric oxide-dependent mechanism. In the present study, we examined the effects of leptin on membrane fluidity of erythrocytes in subjects with essential hypertension by means of an electron paramagnetic resonance (EPR) and spin-labeling method. The values of the order parameter (S) and the peak height ratio (ho/h-1) obtained from the EPR spectra of erythrocytes were significantly greater in patients with essential hypertension (HT) than in age-matched normotensive subjects (NT) (S: HT 0.719 +/- 0.002, n = 16, NT 0.713 +/- 0.001, n = 29, P < .05; ho/h-1: HT 5.17 +/- 0.02, n = 16, NT 5.05 +/- 0.02, n = 29, P < .05). The finding indicated that the erythrocyte membrane fluidity was lower in patients with HT than in NT. Leptin decreased S and ho/h-1 in a dose-dependent manner in both NTs and HTs. The effect of leptin on the membrane fluidity was significantly more pronounced in HTs than in NTs (percent change in S: leptin 10(-8) g/mL, HT -3.4% +/- 0.2%, n = 16, NT -2.3% +/- 0.1%, n = 29, P < .05; leptin 10(-7) g/mL, HT -4.3% +/- 0.3%, n = 16, NT -3.3% +/- 0.1%, n = 29, P < .05). The results of the present study showed that leptin might have a crucial role in the regulation of the rheologic behavior of erythrocytes and the microcirculation in hypertension.

摘要

有迹象表明,人类肥胖基因的产物瘦素不仅积极参与代谢调节,还参与血压控制。最近,有人提出细胞膜物理性质的异常可能是与高血压、中风和其他心血管疾病密切相关的缺陷的基础。我们之前已经表明,瘦素通过一氧化氮依赖机制显著增加了人类红细胞的膜流动性并改善了其微粘度。在本研究中,我们通过电子顺磁共振(EPR)和自旋标记法研究了瘦素对原发性高血压患者红细胞膜流动性的影响。原发性高血压(HT)患者红细胞EPR光谱获得的序参数(S)和峰高比(ho/h-1)值显著高于年龄匹配的血压正常受试者(NT)(S:HT 0.719±0.002,n = 16,NT 0.713±0.001,n = 29,P <.05;ho/h-1:HT 5.17±0.02,n = 16,NT 5.05±0.02,n = 29,P <.05)。这一发现表明,HT患者的红细胞膜流动性低于NT患者。瘦素在NT和HT中均以剂量依赖方式降低S和ho/h-1。瘦素对膜流动性的影响在HT中比在NT中更为明显(S的变化百分比:瘦素10(-8) g/mL,HT -3.4%±0.2%,n = 16,NT -2.3%±0.1%,n = 29,P <.05;瘦素10(-7) g/mL,HT -4.3%±0.3%,n = 16,NT -3.3%±0.1%,n = 29,P <.05)。本研究结果表明,瘦素可能在高血压中红细胞流变行为和微循环的调节中起关键作用。

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