De Franceschi L, Beuzard Y, Jouault H, Brugnara C
Department of Internal Medicine, University of Verona, Italy.
Blood. 1996 Oct 1;88(7):2738-44.
Prevention of erythrocyte dehydration is a potential therapeutic strategy for sickle cell disease. Increasing erythrocyte magnesium (Mg) could inhibit sickle cell dehydration by increasing chloride (CI) and water content and by inhibiting potassium chloride (K-CI) cotransport. In transgenic SAD 1 and (control) C57BL/6 normal mice, we investigated the effect of 2 weeks of diet with either low Mg (6 +/- 2 mg/kg body weight/d) or high Mg (1,000 +/- 20 mg/kg body weight/ d), in comparison with a diet of standard Mg (400 +/- 20 mg/ kg body weight/d). The high-Mg diet increased SAD 1 erythrocyte Mg and K contents and reduced K-CI cotransport activity, mean corpuscular hemoglobin concentration (MCHC), cell density, and reticulocyte count. SAD 1 mice treated with low-Mg diet showed a significant reduction in erythrocyte Mg and K contents and increases in K-CI cotransport, MCHC, cell density, and reticulocyte counts. In SAD 1 mice, hematocrit (Hct) and hemoglobin (Hb) decreased significantly with low Mg diet and increased significantly with high-Mg diet. The C57BL/6 controls showed significant changes only in erythrocyte Mg and K content, and K-CI cotransport activities, similar to those observed in SAD 1 mice. Thus, in the SAD 1 mouse, changes in dietary Mg modulate K-CI cotransport, modify erythrocyte dehydration, and ultimately affect Hb levels.
预防红细胞脱水是镰状细胞病的一种潜在治疗策略。增加红细胞内的镁(Mg)可以通过增加氯(CI)和水含量以及抑制氯化钾(K-CI)协同转运来抑制镰状细胞脱水。在转基因SAD 1小鼠和(对照)C57BL/6正常小鼠中,我们研究了与标准镁饮食(400±20 mg/kg体重/天)相比,低镁饮食(6±2 mg/kg体重/天)或高镁饮食(1000±20 mg/kg体重/天)喂养2周的效果。高镁饮食增加了SAD 1小鼠红细胞的镁和钾含量,降低了K-CI协同转运活性、平均红细胞血红蛋白浓度(MCHC)、细胞密度和网织红细胞计数。低镁饮食处理的SAD 1小鼠红细胞的镁和钾含量显著降低,K-CI协同转运、MCHC、细胞密度和网织红细胞计数增加。在SAD 1小鼠中,低镁饮食时血细胞比容(Hct)和血红蛋白(Hb)显著降低,高镁饮食时则显著增加。C57BL/6对照小鼠仅在红细胞镁和钾含量以及K-CI协同转运活性方面出现显著变化,与SAD 1小鼠中观察到的情况相似。因此,在SAD 1小鼠中,饮食中镁的变化调节K-CI协同转运,改变红细胞脱水,最终影响血红蛋白水平。