Trachtman H, Chan J C, Chan W, Valderrama E, Brandt R, Wakely P, Futterweit S, Maesaka J, Ma C
Department of Pediatrics (Division of Nephrology), Schneider Children's Hospital, New Hyde Park New York 11040, USA.
Pediatr Res. 1996 Oct;40(4):620-6. doi: 10.1203/00006450-199610000-00018.
IgA nephropathy is one of the most common forms of glomerular disease. Nearly 25% of affected patients progress to end-stage renal disease over a 20-25-y follow-up period. IgA-containing immune complexes stimulate oxygen-free radical production by mesangial cells in vitro. The excessive oxidant stress may mediate glomerular injury in this disorder. Therefore, we studied whether dietary supplementation with the antioxidant agent, vitamin E, attenuates renal disease in an experimental model of incipient IgA nephropathy with mild kidney inflammation. IgA nephropathy was induced in male Lewis rats by oral immunization with 0.1% bovine gamma-globulin (BGG)-containing drinking water for 8 wk. At the completion of this period, animals received BGG, 1 mg/dose i.v., on three successive days. Experimental rats (n = 10) received a specially formulated diet containing 100 IU of vitamin E/kg of chow, whereas control animals (n = 10) were fed chow containing 30 IU of vitamin/kg of chow. The BGG immunization regimen induced mesangial IgA deposition in all rats. Vitamin E supplementation resulted in a nearly 5-fold increase in the serum vitamin E concentration. Vitamin E-treated rats gained more weight and had a lower incidence of hematuria, 20% versus 80% (p < 0.03). Moreover, proteinuria was decreased by 50%, and reduced renal plasma flow was restored to normal, compared with untreated rats with IgA nephropathy. Glomerular hypertrophy occurred in animals with IgA nephropathy, but less so in those receiving vitamin E supplementation. Renal cortical malondialdehyde content was reduced from 1.55 +/- 0.10 to 1.22 +/- 0.09 nmol/mg of protein (p < 0.01) in rats fed the vitamin E-enriched diet. Finally, renal transforming growth factor-beta 1 gene expression was reduced by 34% in rats with IgA nephropathy receiving vitamin E treatment (p < 0.05). We conclude that experimental IgA nephropathy is associated with increased renal oxidant injury. Dietary treatment with the antioxidant agent, vitamin E, attenuated renal functional and structural changes in this experimental glomerulopathy. These studies support the importance of clinical trials for the evaluation of the efficacy of antioxidant therapy in patients with IgA nephropathy.
IgA肾病是最常见的肾小球疾病形式之一。在20至25年的随访期内，近25%的受影响患者会进展至终末期肾病。含IgA的免疫复合物在体外刺激系膜细胞产生氧自由基。这种疾病中过量的氧化应激可能介导肾小球损伤。因此，我们研究了在轻度肾脏炎症的早期IgA肾病实验模型中，补充抗氧化剂维生素E是否能减轻肾脏疾病。通过用含0.1%牛γ球蛋白（BGG）的饮用水口服免疫雄性Lewis大鼠8周来诱导IgA肾病。在此期间结束时，动物连续三天静脉注射1mg/剂量的BGG。实验大鼠（n = 10）接受含有100IU维生素E/kg食物的特殊配方饮食，而对照动物（n = 10）喂食含有30IU维生素E/kg食物的普通食物。BGG免疫方案在所有大鼠中诱导了系膜IgA沉积。补充维生素E导致血清维生素E浓度增加近5倍。维生素E治疗的大鼠体重增加更多，血尿发生率更低，分别为20%和80%（p < 0.03）。此外，与未治疗的IgA肾病大鼠相比，蛋白尿减少了50%，肾血浆流量恢复正常。IgA肾病动物出现肾小球肥大，但在接受维生素E补充的动物中程度较轻。喂食富含维生素E饮食的大鼠肾皮质丙二醛含量从1.55±0.10降至1.22±0.09nmol/mg蛋白质（p < 0.01）。最后，接受维生素E治疗的IgA肾病大鼠肾转化生长因子-β1基因表达降低了34%（p < 0.05）。我们得出结论，实验性IgA肾病与肾脏氧化损伤增加有关。用抗氧化剂维生素E进行饮食治疗可减轻这种实验性肾小球病的肾功能和结构变化。这些研究支持了在IgA肾病患者中评估抗氧化治疗疗效的临床试验的重要性。
