Ng L L, Ngkeekwong F C, Quinn P A, Davies J E
Department of Medicine and Therapeutics, Leicester Royal Infirmary, UK.
Diabetologia. 1998 Apr;41(4):435-42. doi: 10.1007/s001250050927.
In diabetic nephropathy and hypertension, a major cause of mortality is from cardiovascular disease. Since low levels of antioxidants such as vitamin C have been associated with such complications, we have examined the uptake mechanisms for ascorbic acid (AA) and dehydroascorbic acid (DHA) in lymphoblasts from normal control subjects (CON), normoalbuminuric insulin-dependent diabetic (IDDM) patients (DCON), patients with IDDM and nephropathy (DN) and hypertensive patients (HT) using mass assays of uptake and measuring AA using high-performance liquid chromatography. Precautions were taken to prevent oxidation of AA and to take into account the instability of DHA in buffers. DHA uptake was the major mechanism in all four groups of subjects, and the Vmax (maximal uptake rate) was significantly lower in the DN cells (24.7 +/- 1.0 nmol [95% confidence intervals CI 22.5, 26.3] 10(6) cells(-1) h(-1)) compared to CON and DCON cells (33.9 +/- 2.1 [95% CI 29.4, 38.4] and 37.0 +/- 2.2 [95% CI 32.2, 41.8] nmol 10(6) cells(-1) h(-1), respectively, p < 0.001 for both). DHA Vmax was also lower in the HT group (23.2 +/- 1.1 [95% CI 20.7, 25.7] nmol 10(6) cells(-1) h(-1)) compared to the CON group (p < 0.001). There were no significant differences in the Km or passive membrane permeability for DHA or the AA uptake. DHA uptake showed a negative correlation to systolic blood pressure (r(s) = -0.49, p < 0.001). These findings suggest that impaired DHA uptake may be one component of the phenotype expressed by DN cells that may persist in culture. Impaired DHA uptake in vivo, especially in the presence of hyperglycaemia, leads to impaired regeneration of AA and depletion of anti-oxidant defences, exposing such individuals to increased risk of cardiovascular disease.
在糖尿病肾病和高血压中，主要的死亡原因是心血管疾病。由于低水平的抗氧化剂（如维生素C）与这些并发症有关，我们使用摄取量的质量分析法，并通过高效液相色谱法测量抗坏血酸（AA），研究了正常对照受试者（CON）、正常白蛋白尿胰岛素依赖型糖尿病（IDDM）患者（DCON）、IDDM合并肾病患者（DN）和高血压患者（HT）的淋巴母细胞中抗坏血酸（AA）和脱氢抗坏血酸（DHA）的摄取机制。采取了预防措施以防止AA氧化，并考虑到DHA在缓冲液中的不稳定性。DHA摄取是所有四组受试者的主要摄取机制，与CON和DCON细胞相比，DN细胞中的Vmax（最大摄取率）显著较低（24.7±1.0 nmol[95%置信区间CI 22.5, 26.3] 10⁶细胞⁻¹ h⁻¹）（CON和DCON细胞分别为33.9±2.1[95%CI 29.4, 38.4]和37.0±2.2[95%CI 32.2, 41.8] nmol 10⁶细胞⁻¹ h⁻¹，两者p均<0.001）。与CON组相比，HT组的DHA Vmax也较低（23.2±1.1[95%CI 20.7, 25.7] nmol 10⁶细胞⁻¹ h⁻¹）（p<0.001）。DHA或AA摄取的Km或被动膜通透性没有显著差异。DHA摄取与收缩压呈负相关（r(s)= -0.49，p<0.001）。这些发现表明，DHA摄取受损可能是DN细胞所表现出的表型的一个组成部分，并且可能在培养中持续存在。体内DHA摄取受损，尤其是在存在高血糖的情况下，会导致AA再生受损和抗氧化防御能力耗尽，使这些个体面临心血管疾病风险增加的情况。
