他汀类药物治疗对人红细胞膜引起的物理化学修饰。

Physicochemical modifications induced by statins therapy on human erythrocytes membranes.

作者信息

Broncel Marlena, Bała Agnieszka, Koter-Michalak Maria, Duchnowicz Piotr, Wojsznis Waldemar, Chojnowska-Jezierska Julita

机构信息

Department of Internal Diseases with Clinical Pharmacology and Therapy Monitoring Unit, University of Lodz, Poland.

出版信息

Wiad Lek. 2007;60(7-8):321-8.

PMID:18175550

Abstract

UNLABELLED

In hyperlipidemia damage to the plasma membranes of erythrocytes is observed. It is supposed that statins by their beneficial impact on the serum lipids and pleiotropic effects may modify the membrane cell structure.

MATERIAL AND METHODS

The aim of the study was to evaluate the effects of statins on erythrocyte membrane structure in patients (pts) with hyperlipidemia. The study involved 54 pts with the initial total cholesterol (TC) concentration > 200 mg/dl (6.5 mmol/l), low-density lipoprotein cholesterol (LDL-C) > 160 mg/dl (4.1 mmol/l) and triglycerides (TG) < 400 mg/dl (4.5 mmol/l) and 22 healthy individuals as the control group. After 8 weeks of hypolipemic diet, pts were randomized to two groups: A--27 pts treated with atorvastatin in a dose of 10 mg/day; S--27 pts treated with simvastatin in a dose of 40 mg/day. After 8 weeks of active therapy in all pts were determined: the activity of Na+K+-ATPase, erythrocyte membrane fluidity (the order parameter S), lipids peroxidation (thiobarbituric acid-reactive substances - TBARS), content of membrane cholesterol, concentration of SH groups and W/S ratio (which specifies the relations between the two kinds of the SH groups: the weakly--W bound, and the strongly--S bound).

RESULTS

In the group of hyperlipidemic patients as compared to the control group we observed significantly higher values of the order parameter S, membrane cholesterol, TBARS, ratio W/S and significantly lower the activity of Na+K+-ATPase, SH groups concentration in membrane erythrocytes. Atorvastatin and simvastatin in a similar degree significantly increased the activity of Na'K'-ATPase (15.7% vs. 20.9%), the SH concentration groups (23.4% vs. 21.2%) and decreased TBARS (-41.8% vs. -41%), W/S ratio (-11.3% vs. S-12.1%). Simvastatin decreased stronger the membrane cholesterol (-30.0% vs. -24.5%; p < 0.05) and the values of parameter S (-5.1% vs. -3.5%, p < 0.05) than atorvastatin.

CONCLUSIONS

A short-term therapy with statins exhibits a high hypolipemic efficacy and advantageous effects on the protein-lipid structure of erythrocyte membranes. Simvastatin at 40 mg/day dose increases the fluidity of erythrocyte membrane and decreases the membrane cholesterol level to a greater extent than does atorvastatin at 10 mg/day dose.

摘要

未标记

在高脂血症中可观察到红细胞质膜受损。据推测，他汀类药物因其对血脂的有益影响和多效性作用，可能会改变细胞膜结构。

材料与方法

本研究的目的是评估他汀类药物对高脂血症患者红细胞膜结构的影响。该研究纳入了54例初始总胆固醇（TC）浓度>200mg/dl（6.5mmol/l）、低密度脂蛋白胆固醇（LDL-C）>160mg/dl（4.1mmol/l）且甘油三酯（TG）<400mg/dl（4.5mmol/l）的患者，以及22名健康个体作为对照组。经过8周的低脂饮食后，患者被随机分为两组：A组——27例患者接受10mg/天剂量的阿托伐他汀治疗；S组——27例患者接受40mg/天剂量的辛伐他汀治疗。在所有患者进行8周的积极治疗后，测定了以下指标：Na⁺K⁺-ATP酶活性、红细胞膜流动性（序参数S）、脂质过氧化（硫代巴比妥酸反应性物质——TBARS）、膜胆固醇含量、SH基团含量以及W/S比值（该比值确定了两种SH基团之间的关系：弱结合的——W，和强结合的——S）。

结果

与对照组相比，高脂血症患者组的序参数S、膜胆固醇、TBARS、W/S比值显著更高，而红细胞膜中Na⁺K⁺-ATP酶活性、SH基团浓度显著更低。阿托伐他汀和辛伐他汀在相似程度上显著提高了Na⁺K⁺-ATP酶活性（分别为15.7%和20.9%）、SH基团浓度（分别为23.4%和21.2%），并降低了TBARS（分别为-41.8%和-41%）、W/S比值（分别为-11.3%和-12.1%）。辛伐他汀比阿托伐他汀更显著地降低了膜胆固醇（分别为-30.0%和-24.5%；p<0.05）以及参数S的值（分别为-5.1%和-3.5%，p<0.05）。