Fredriksen J, Ueland T, Dyrøy E, Halvorsen B, Melby K, Melbye L, Skalhegg B S, Bohov P, Skorve J, Berge R K, Aukrust P, Frøland S S
Rikshospitalet, Oslo, Norway.
Eur J Clin Invest. 2004 Oct;34(10):709-15. doi: 10.1111/j.1365-2362.2004.01410.x.
Highly active antiretroviral therapy (HAART) often leads to a dramatic improvement in clinical, viral and immunologic parameters in HIV-infected individuals. However, the emergence of long-term side-effects of HAART and in particular dylipidaemia is increasingly reported. Based on the potential lipid-lowering and immunomodulatory properties of tetradecylthioacetic acid (TTA) we examined whether TTA in combination with dietary intervention could modify lipid levels in peripheral blood in HIV-infected patients on HAART.
Ten HIV-infected patients on protease inhibitor-based HAART with hyperlipidaemia followed a cholesterol-lowering diet throughout the study period (8 weeks). During the last 4 weeks of the study all patients received TTA (1 g qd) in addition to the cholesterol-lowering diet.
Our main and novel findings were: (i) TTA in combination with dietary intervention reduces total cholesterol, LDL cholesterol, triglycerides and LDL/HDL cholesterol in these patients, and a particularly suppressing effect was observed during the TTA phase regarding total cholesterol. (ii) During the TTA phase, the cholesterol-lowering effect was accompanied by a significant reduction in plasma levels of tumour necrosis factor alpha. (iii) Our studies in peripheral blood mononuclear cells from these patients and in the liver from wild-type mice receiving TTA suggest that the hypolipidaemic effects of TTA may involve up-regulation of scavenger and LDL-receptor expression.
Although few patients were studied, the present pilot study suggests that TTA combined with dietary intervention could be an interesting therapeutic approach in HIV-infected patients on HAART, potentially resulting in both hypolipidaemic and anti-inflammatory effects.
高效抗逆转录病毒疗法(HAART)通常会使HIV感染个体的临床、病毒学和免疫学参数得到显著改善。然而,HAART长期副作用的出现,尤其是血脂异常的报道越来越多。基于十四烷基硫代乙酸(TTA)潜在的降脂和免疫调节特性,我们研究了TTA联合饮食干预是否能改变接受HAART的HIV感染患者外周血中的血脂水平。
10名接受基于蛋白酶抑制剂的HAART且患有高脂血症的HIV感染患者在整个研究期间(8周)遵循降胆固醇饮食。在研究的最后4周,所有患者除了降胆固醇饮食外,还接受TTA(每日1克)。
我们的主要新发现如下:(i)TTA联合饮食干预可降低这些患者的总胆固醇、低密度脂蛋白胆固醇、甘油三酯以及低密度脂蛋白/高密度脂蛋白胆固醇比值,在TTA阶段观察到对总胆固醇有特别显著的抑制作用。(ii)在TTA阶段,降胆固醇作用伴随着肿瘤坏死因子α血浆水平的显著降低。(iii)我们对这些患者外周血单个核细胞以及接受TTA的野生型小鼠肝脏的研究表明,TTA的降脂作用可能涉及清道夫受体和低密度脂蛋白受体表达的上调。
尽管研究的患者数量较少,但本初步研究表明,TTA联合饮食干预可能是接受HAART的HIV感染患者一种有前景的治疗方法,可能会产生降脂和抗炎双重效果。