阿托伐他汀可下调 2 型糖尿病患者单核细胞 CD36 表达、核 NFkappaB 和 TNFalpha 水平。

Atorvastatin downregulates monocyte CD36 expression, nuclear NFkappaB and TNFalpha levels in type 2 diabetes.

机构信息

Department of Clinical Sciences, Sapienza University of Rome, Rome, Italy.

出版信息

J Atheroscler Thromb. 2010 Jun 30;17(6):539-45. doi: 10.5551/jat.2956. Epub 2010 Feb 5.

DOI:10.5551/jat.2956

PMID:20134099

Abstract

AIM

Type 2 diabetes increases the risk for cardiovascular disease, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce cardiovascular events in these patients. The benefits of statin therapy cannot be explained only by the lipid-lowering effect. The aim of this study was to test the effect of atorvastatin therapy on CD36 scavenger receptor expression, nuclear factor-kappaB (NFkappaB) levels and markers of inflammation (C-reactive protein, CRP, Tumor Necrosis Factor-alpha, TNF-alpha) in circulating monocytes from diabetic patients.

METHODS

Twenty-two type 2 diabetic patients were treated for 8 weeks with atorvastatin (20 mg/day). At baseline and after treatment a blood sample was collected for measurement of glucose, lipid profile (total cholesterol, HDL, LDL cholesterol, triglycerides), glycated hemoglobin (HbA1c), CRP and for isolation of monocytes.

RESULTS

Atorvastatin decreased total (p<0.0001) and LDL (p<0.01), and incresased HDL choles-terol (p<0.02). CD36 surface protein expression (anti-CD36 fluorescein isothiocyanate-FITC) was reduced in circulating monocytes after atorvastatin therapy (p<0.02) while immunoblot analysis showed reduced nuclear and increased cytoplasm NFkappaB levels (p<0.05). Finally, TNFalpha production in lipopolysaccharide-activated monocytes from patients treated with atorvastatin was reduced (p<0.05).

CONCLUSION

These results suggest that atorvastatin therapy, beside lowering serum cholesterol levels, could exert anti-atherogenic and anti-inflammatory effects in type 2 diabetic patients.

摘要

目的

2 型糖尿病会增加心血管疾病的风险，而 3-羟基-3-甲基戊二酰基辅酶 A（HMG-CoA）还原酶抑制剂（他汀类药物）可降低此类患者的心血管事件发生率。他汀类药物治疗的益处不能仅用降脂作用来解释。本研究旨在检测阿托伐他汀治疗对 2 型糖尿病患者循环单核细胞中 CD36 清道夫受体表达、核因子-κB（NFκB）水平和炎症标志物（C 反应蛋白，CRP，肿瘤坏死因子-α，TNF-α）的影响。

方法

22 例 2 型糖尿病患者接受阿托伐他汀（20mg/天）治疗 8 周。在基线和治疗后采集血样，用于测量血糖、血脂谱（总胆固醇、HDL、LDL 胆固醇、甘油三酯）、糖化血红蛋白（HbA1c）、CRP 并分离单核细胞。

结果

阿托伐他汀降低了总胆固醇（p<0.0001）和 LDL（p<0.01），并增加了 HDL 胆固醇（p<0.02）。阿托伐他汀治疗后，循环单核细胞中 CD36 表面蛋白表达（抗-CD36 异硫氰酸荧光素-FITC）减少（p<0.02），而免疫印迹分析显示核内 NFκB 水平降低和胞质内 NFκB 水平增加（p<0.05）。最后，用脂多糖激活的单核细胞中 TNFα的产生在接受阿托伐他汀治疗的患者中减少（p<0.05）。