Saleh Mohamed A, De Miguel Carmen, Stevens David I, Carmines Pamela K, Pollock David M, Pollock Jennifer S
Medical College of Georgia, Augusta University, Augusta, Georgia.
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Physiol Rep. 2016 Dec;4(24). doi: 10.14814/phy2.13055.
Increased renal endothelin-1 (ET-1) production and an ET receptor-dependent increase in glomerular albumin permeability (P) accompany type 1 diabetes mellitus (T1D). We hypothesized that T1D-induced oxidative stress contributes to renal ET-1 production and glomerular P Male rats with streptozotocin-induced T1D were provided free access to drinking water without additives (T1D rats) or containing the free radical scavenger tempol (1 mmol/L; T1D+Tempol). After 3 weeks, T1D+Tempol rats displayed lower urinary excretion of thiobarbituric acid reactive substances and glomerular superoxide production (dihydroethidium staining) compared to T1D rats. Urinary ET-1 excretion and inner medullary (but not cortical or outer medullary) prepro-ET-1 mRNA expression were lower in the T1D+Tempol group than in the T1D group. P, measured as the change in volume of isolated glomeruli upon exposure to oncotic gradients of albumin, was significantly lower in the T1D+Tempol group than in the T1D group. Tempol treatment did not alter protein excretion or creatinine clearance. These data support the postulate that oxidative stress contributes to glomerular P and renal ET-1 production during the early phase of type 1 diabetes.
1型糖尿病（T1D）伴有肾内皮素-1（ET-1）生成增加以及ET受体依赖性肾小球白蛋白通透性（P）升高。我们推测，T1D诱导的氧化应激促成了肾ET-1生成和肾小球P。给链脲佐菌素诱导的T1D雄性大鼠自由饮用不含添加剂的饮用水（T1D大鼠）或含有自由基清除剂tempol（1 mmol/L；T1D+Tempol）的饮用水。3周后，与T1D大鼠相比，T1D+Tempol大鼠的硫代巴比妥酸反应性物质尿排泄量和肾小球超氧化物生成（二氢乙锭染色）较低。T1D+Tempol组的尿ET-1排泄量和肾内髓质（而非皮质或外髓质）前ET-蛋白原-1 mRNA表达低于T1D组。以暴露于白蛋白胶体渗透压梯度时分离肾小球体积的变化来衡量的P，T1D+Tempol组显著低于T1D组。Tempol治疗未改变蛋白质排泄或肌酐清除率。这些数据支持以下假设：在1型糖尿病早期，氧化应激促成了肾小球P和肾ET-1生成。
