Paris Cardiovascular Centre (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
J Diabetes Res. 2017;2017:9603924. doi: 10.1155/2017/9603924. Epub 2017 Nov 22.
Indirect evidence suggests a role for heme oxygenase-1 (HO-1) in limiting diabetic vasculopathy. The goal of this study was to assess the role of HO-1 in the development of microvascular lesions within glomeruli during diabetes mellitus using a mouse model with specific alteration of the gene.
The effects of haploinsufficiency were studied as a means of assessing the intrinsic contribution of HO-1 in the development of renal microvascular lesions during diabetes. Renal function and histology were analyzed 10 weeks after diabetes induction with streptozotocin. Diabetic mice showed higher levels of albuminuria and blood urea compared to their wild-type diabetic littermates. More severe glomerular microvascular lesions were also observed in the diabetic mice. This was associated with a renal increase in the expression of the oxidative stress marker, nitrotyrosine.
Genetic partial deficiency is sufficient to sensitize mice to the development of diabetic glomerular microvascular lesions. HO-1 exerts antioxidant effects in the kidney during diabetes mellitus. These have protective effects on the development of glomerular endothelial injury.
间接证据表明血红素加氧酶-1（HO-1）在限制糖尿病血管病变中发挥作用。本研究的目的是使用基因特异性改变的小鼠模型评估 HO-1 在糖尿病期间肾小球内微血管病变发展中的作用。
作为评估 HO-1 在糖尿病期间肾脏微血管病变发展中固有作用的一种手段，研究了 HO-1 杂合不足的影响。在链脲佐菌素诱导糖尿病 10 周后分析肾功能和组织学。与野生型糖尿病同窝仔相比，糖尿病 小鼠表现出更高的白蛋白尿和血尿素水平。在糖尿病 小鼠中也观察到更严重的肾小球微血管病变。这与肾脏中氧化应激标志物硝基酪氨酸的表达增加有关。
基因部分缺乏足以使小鼠易患糖尿病肾小球微血管病变。HO-1 在糖尿病期间在肾脏中发挥抗氧化作用。这些对肾小球内皮损伤的发展具有保护作用。
