Cosson Emmanuel, Cohen-Boulakia Francine, Tarhzaoui Karima, Dabiré Hubert, Léger Gérard, Charnaux Nathalie, Lestrade Roger, Behar Abraham, Valensi Paul
Laboratory of Nutrition, Metabolic Diseases and Cardiovascular Prevention, Faculté de médecine Léonard de Vinci, Bobigny, France.
Microvasc Res. 2009 Mar;77(2):220-5. doi: 10.1016/j.mvr.2008.11.005. Epub 2008 Dec 3.
If thiazolidinediones have shown beneficial effects on macrovascular endothelial function, their effects on microcirculation and lymphatic function are not well documented. The aim of the study was to assess the effect of rosiglitazone on interstitial albumin retention and lymphatic function in Zucker Diabetic Fatty (ZDF) rats. Three series of 9-14 rats were studied: Lean (fa/?) controls, ZDF (Gmi-fa/fa) rats and ZDF rats treated with rosiglitazone from 8 to 26 weeks of age (ZDF-ROSI). Albumin retention and lymphatic uptake of interstitial albumin (LF/HF ratio) were evaluated on hindquarters with a noninvasive isotopic test using technetium-labelled albumin. Vascular Endothelial Growth Factor (VEGF) was measured. At week 25, albumin retention was markedly higher in ZDF rats (9.9+/-1.0%) than in control rats (1.0+/-0.8%, p<0.001), but did not differ significantly between the ZDF-ROSI group (2.5+/-1.5%) and the control group. LF/HF ratio was similarly increased in the ZDF group (1.14+/-0.07%) and the ZDF-ROSI group (1.07+/-0.04%) as compared to control rats (0.65+/-0.04%; p<0.001 for both). We can deduce that the prevention of the increase of albumin retention under rosiglitazone results from a decrease in the capillary filtration of albumin. VEGF levels were 7.1+/-1.5, 7.3+/-1.9, 3.5+/-1.6 pg/mL in the control, ZDF and ZDF-ROSI groups, respectively (p=0.23). In ZDF rats, rosiglitazone prevents interstitial albumin retention and the increase in capillary filtration of albumin. However lymphatic function is still impaired and might contribute to oedema.
如果噻唑烷二酮类药物已显示出对大血管内皮功能有有益作用，那么它们对微循环和淋巴功能的影响尚无充分的文献记载。本研究的目的是评估罗格列酮对Zucker糖尿病肥胖（ZDF）大鼠间质白蛋白潴留和淋巴功能的影响。研究了三组9 - 14只大鼠：瘦型（fa/?）对照大鼠、ZDF（Gmi - fa/fa）大鼠以及从8至26周龄用罗格列酮治疗的ZDF大鼠（ZDF - ROSI）。使用锝标记的白蛋白通过非侵入性同位素试验评估后肢的白蛋白潴留和间质白蛋白的淋巴摄取（LF/HF比值）。检测血管内皮生长因子（VEGF）。在第25周时，ZDF大鼠的白蛋白潴留（9.9±1.0%）显著高于对照大鼠（1.0±0.8%，p<0.001），但ZDF - ROSI组（2.5±1.5%）与对照组之间无显著差异。与对照大鼠（0.65±0.04%）相比，ZDF组（1.14±0.07%）和ZDF - ROSI组（1.07±0.04%）的LF/HF比值同样升高（两者p<0.001）。我们可以推断，罗格列酮治疗下白蛋白潴留增加的预防是由于白蛋白毛细血管滤过的减少。对照组、ZDF组和ZDF - ROSI组的VEGF水平分别为7.1±1.5、7.3±1.9、3.5±1.6 pg/mL（p = 0.23）。在ZDF大鼠中，罗格列酮可预防间质白蛋白潴留和白蛋白毛细血管滤过的增加。然而，淋巴功能仍然受损，可能导致水肿。
