Sachet J C, Borba E F, Bonfá E, Vinagre C G C, Silva V M, Maranhão R C
Rheumatology Division and Lipid Metabolism Laboratory, Heart Institute (InCor), Medical School Hospital and Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Lupus. 2007;16(4):273-8. doi: 10.1177/09612033070160040901.
Low-density lipoprotein (LDL) pathway in systemic lupus erythematosus (SLE) patients taking chloroquine diphosphate (CDP) was evaluated through the kinetic behavior of a radioactive cholesterol-rich nanoemulsion (LDE) that resembles the LDL lipidic structure. LDE was labeled with (14)C-cholesteryl ester ((14)C-CE), then IV injected in inactive female SLE patients: 10 taking CDP (CDP), 10 without therapy (NO THERAPY); and 10 normal subjects (CONTROL). Groups were age-matched and followed rigorous selection criteria of conditions that interfere in the lipid profile. Blood samples were collected in pre-established intervals after infusion for radioactivity measurement. Fasting lipoproteins were determined in the beginning of kinetic studies. Fractional clearance rate (FCR) of (14)C-CE was significantly different in the three groups (P = 0.03). In fact, a greater FCR of (14)C-CE was observed in CDP compared to NO THERAPY (0.076 +/- 0.037 versus 0.046 +/- 0.021 h(-1); P < 0.05) and to CONTROL (0.0516 +/- 0.0125 h(-1); P < 0.05). Accordingly, a significant lower total and LDL cholesterol were observed in CDP (156 +/- 16 and 88 +/- 16 mg/dl) compared to NO THERAPY (174 +/- 15 and 108 +/- 17 mg/dl; P < 0.05) and to CONTROL (200 +/- 24 and 118 +/- 23 mg/dl; P < 0.05). In contrast, no difference in (FCR) of (14)C-CE of NO THERAPY and CONTROL groups was observed. This is the first in vivo demonstration that LDE removal by LDL receptor from plasma is increased in SLE patients taking CDP with a consequent beneficial decrease in LDL-c levels.
通过一种类似于低密度脂蛋白（LDL）脂质结构的富含放射性胆固醇的纳米乳剂（LDE）的动力学行为，评估了服用二磷酸氯喹（CDP）的系统性红斑狼疮（SLE）患者的LDL途径。LDE用（14）C - 胆固醇酯（（14）C - CE）标记，然后静脉注射给无活动期的女性SLE患者：10名服用CDP（CDP组），10名未接受治疗（未治疗组）；以及10名正常受试者（对照组）。各组年龄匹配，并遵循严格的干扰血脂状况的选择标准。输注后按预先设定的时间间隔采集血样进行放射性测量。在动力学研究开始时测定空腹脂蛋白。三组中（14）C - CE的分数清除率（FCR）有显著差异（P = 0.03）。实际上，与未治疗组相比，CDP组观察到更高的（14）C - CE的FCR（0.076±0.037对0.046±0.021 h-1；P < 0.05），与对照组相比也是如此（0.0516±0.0125 h-1；P < 0.05）。因此，与未治疗组（174±15和108±17 mg/dl；P < 0.05）和对照组（200±24和118±23 mg/dl；P < 0.05）相比，CDP组观察到显著更低的总胆固醇和LDL胆固醇（156±16和88±16 mg/dl）。相反，未治疗组和对照组的（14）C - CE的FCR没有差异。这是首次在体内证明，服用CDP的SLE患者中，LDL受体从血浆中清除LDE增加，从而使LDL - c水平有益降低。
