Grubb Jessica R, Dejam André, Voell Jocelyn, Blackwelder William C, Sklar Peter A, Kovacs Joseph A, Cannon Richard O, Masur Henry, Gladwin Mark T
Critical Care Medical Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Infect Dis. 2006 Jun 1;193(11):1516-9. doi: 10.1086/503807. Epub 2006 Apr 27.
To differentiate between the effects that antiretroviral drugs have on the endothelium and the secondary effects that they have on immune function, viral load, and dyslipidemia, 6 non-human immunodeficiency virus-infected human subjects were treated with lopinavir-ritonavir for 1 month and, on the basis of forearm blood flow, the treatment's effects on endothelial cell function were measured. Surprisingly, after exposure to lopinavir-ritonavir, absolute forearm blood-flow responses to the endothelium-dependent vasodilator, acetylcholine, increased significantly (P=.03), and forearm blood flow decreased to a greater extent during specific inhibition of NO synthase by N(G)-monomethyl-L-arginine. Thus, in this small cohort of subjects, short-term treatment with lopinavir-ritonavir does not appear to directly promote endothelial cell dysfunction.
为了区分抗逆转录病毒药物对内皮的影响以及它们对免疫功能、病毒载量和血脂异常的次要影响,6名未感染人类免疫缺陷病毒的受试者接受了洛匹那韦-利托那韦治疗1个月,并根据前臂血流量测量该治疗对内皮细胞功能的影响。令人惊讶的是,在接触洛匹那韦-利托那韦后,对内皮依赖性血管扩张剂乙酰胆碱的绝对前臂血流反应显著增加(P = 0.03),并且在N(G)-单甲基-L-精氨酸特异性抑制一氧化氮合酶期间,前臂血流量下降幅度更大。因此,在这一小群受试者中,短期使用洛匹那韦-利托那韦治疗似乎不会直接促进内皮细胞功能障碍。