Setti Giorgia, Hayward Anthea, Dessapt Cecile, Barone Francesca, Buckingham Robin, White Kathryn, Bilous Rudolf, Hiroshi Kawachi, Gruden Gabriella, Viberti GianCarlo, Gnudi Luigi
Cardiovascular Division, King's College London, London, UK.
Am J Nephrol. 2010;32(5):393-402. doi: 10.1159/000320129. Epub 2010 Sep 3.
BACKGROUNDS/AIMS: Renal inflammation and nephrin downregulation contribute to albuminuria in diabetes. We studied, in streptozotocin-induced diabetic rats, the effect of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-γ agonist, on renal macrophage infiltration, MCP1, and nephrin expression in relation to albuminuria.
We investigated control and diabetic rats treated or untreated with RSG. Animals were sacrificed at 1, 3, and 9 months. Renal MCP1 and nephrin expression were studied by immunoblotting, renal macrophage infiltration by immunohistochemistry, and albuminuria by ELISA. Electron microscopy was used to assess glomerular ultrastructural morphology. In vitro experiments were conducted in isolated cultured rat glomeruli.
Glycaemic control was similar in diabetic rats treated and untreated with RSG, and blood pressure was comparable in all groups. RSG prevented diabetes-induced albuminuria at 9 months, and renal macrophage infiltration and MCP1 upregulation at 3 and 9 months. Diabetes-mediated nephrin downregulation was abolished by RSG. Diabetes-induced glomerulosclerosis, glomerular basement membrane thickening, and foot process fusion were not affected by RSG. In isolated glomeruli, MCP1 directly induced nephrin downregulation and this was prevented by RSG. RSG had no effect on nephrin expression.
RSG prevents albuminuria and nephrin downregulation in experimental diabetes independently of glycaemic and blood pressure control. This effect likely occurs via correction of diabetes-induced inflammatory processes.
背景/目的：肾脏炎症和nephrin下调促成糖尿病中的蛋白尿。我们在链脲佐菌素诱导的糖尿病大鼠中研究了罗格列酮（RSG）（一种过氧化物酶体增殖物激活受体γ激动剂）对肾脏巨噬细胞浸润、单核细胞趋化蛋白1（MCP1）以及与蛋白尿相关的nephrin表达的影响。
我们研究了接受或未接受RSG治疗的对照大鼠和糖尿病大鼠。在1、3和9个月时处死动物。通过免疫印迹研究肾脏MCP1和nephrin表达，通过免疫组织化学研究肾脏巨噬细胞浸润，通过酶联免疫吸附测定法研究蛋白尿。使用电子显微镜评估肾小球超微结构形态。在分离培养的大鼠肾小球中进行体外实验。
接受和未接受RSG治疗的糖尿病大鼠的血糖控制相似，且所有组的血压相当。RSG在9个月时预防了糖尿病诱导的蛋白尿，在3和9个月时预防了肾脏巨噬细胞浸润和MCP1上调。RSG消除了糖尿病介导的nephrin下调。糖尿病诱导的肾小球硬化、肾小球基底膜增厚和足突融合不受RSG影响。在分离的肾小球中，MCP1直接诱导nephrin下调，而RSG可预防这种情况。RSG对nephrin表达无影响。
RSG在实验性糖尿病中独立于血糖和血压控制预防蛋白尿和nephrin下调。这种作用可能通过纠正糖尿病诱导的炎症过程而发生。
