Latta Kay, Krieg Richard J, Carbajo-Pérez Eduardo, Carbajo Santiago, Chan James C M
Department of Pediatrics, Medical College of Virginia, Richmond, VA, USA.
Life Sci. 2002 Sep 6;71(16):1951-60. doi: 10.1016/s0024-3205(02)01963-x.
Deflazacort is a relatively new glucocorticoid with significant immunosuppressant activity and presumably fewer side effects. The present study was designed to compare the effects of deflazacort on the proliferative activity of thymus cells and thymolysis with the growth inhibition. We treated Long-Evans rats for nine days with cortisone (CORT, 5.0 mg/day), deflazacort (DFZ, 0.15 mg/day), and control vehicle (CTRL). Animals were sacrificed 1 hour after injection of bromodeoxyuridine (BrdUrd) on day 10. BrdUrd-labeled thymic cells were quantified without knowledge of treatment. A Labeling Index (LI), expressed as the number of BrdUrd BrdUrd-labeled cells per 100 total cells and the Numerical Density (ND), expressed as the total number of cells per 100 microm(2) were calculated. Treatment with either glucocorticoid resulted in a significant and equal decrease of thymus weight, indicating a marked reduction in total immunogenic tissue. A general alteration of thymic histological structure occurred in the CORT group. The LI was not different between CTRL and DFZ groups, 6.9 and 7.9% of cells were labeled respectively. In the CORT group, the LI was 2.5%. With respect to Numerical Density, the CTRL group had the greatest value (14.6 +/- 0.4 cells/100 microm(2)), with the DFZ (12.3 +/- 0.06 cells/100 microm(2)) and CORT groups being significantly lower (10.4 +/- 0.5 cells/100 microm(2)). Although regression analysis of thymus weight pointed to bioequivalence of the glucocorticoid dosages used, BrdUrd-labeling raised the possibility that the cells still present in the thymus of DFZ-treated animals retained, at least partially, their normal capacities for proliferation.
地夫可特是一种相对较新的糖皮质激素,具有显著的免疫抑制活性,且副作用可能较少。本研究旨在比较地夫可特对胸腺细胞增殖活性和胸腺溶解的影响以及生长抑制作用。我们用可的松(CORT,5.0毫克/天)、地夫可特(DFZ,0.15毫克/天)和对照载体(CTRL)对Long-Evans大鼠进行了九天的治疗。在第10天注射溴脱氧尿苷(BrdUrd)1小时后处死动物。在不知道治疗情况的前提下,对BrdUrd标记的胸腺细胞进行定量。计算标记指数(LI),以每100个总细胞中BrdUrd标记的细胞数表示,以及数值密度(ND),以每100平方微米中的细胞总数表示。两种糖皮质激素治疗均导致胸腺重量显著且同等程度的下降,表明总的免疫原性组织明显减少。CORT组胸腺组织结构发生了普遍改变。CTRL组和DFZ组的LI无差异,分别有6.9%和7.9%的细胞被标记。在CORT组,LI为2.5%。关于数值密度,CTRL组的值最大(14.6±0.4个细胞/100平方微米),DFZ组(12.3±0.06个细胞/100平方微米)和CORT组显著更低(10.4±0.5个细胞/100平方微米)。尽管胸腺重量的回归分析表明所使用的糖皮质激素剂量具有生物等效性,但BrdUrd标记提示,在DFZ治疗的动物胸腺中仍存在的细胞至少部分保留了其正常的增殖能力。