糖尿病是导致终末期肾衰竭的主要原因,以肾脏炎症和肾小球功能障碍为特征,在全世界。肾脏炎症与促炎分子表达水平的改变有关,如核因子-κB(NFκB)和粘附分子,例如E-cadherin,导致肾小球功能障碍。然而,在人类糖尿病肾病中,这两个过程之间的关系仍然是一个悬而未决的问题。由于Psammomysobesus是研究糖尿病时间演变的理想动物模型,我们利用该模型研究了肾脏结构改变与随时间变化的NFκB和E-cadherin表达水平修饰之间的相关性。我们已经证明,用高能量饮食(HED)诱导糖尿病后,P.obesus发展人类疾病的特征性症状。详细来说,第3个月核因子NFκB在糖尿病大鼠肾脏表达及肾脏结构改变,如肾小球系膜扩张或间质纤维化,可检测到;在6个月时,肾小球基底膜增厚,肾小球硬化,发生肾小管萎缩;在9个月时,疾病最后阶段的症状,例如E-cadherin的下调表达,发生。作为这些观察的结果,我们提出NFκB激活和E-钙粘蛋白下调与糖尿病肾病(DKD)相关。
Diabetes mellitus is a major leading cause of end-stage renal failure, characterized by kidney inflammation and glomerular dysfunction, in worldwide. Kidney inflammation is associated to modifications in the expression levels of pro-inflammatory molecules, such as nuclear factor-κB (NFκB) and adhesion molecules, such as E-cadherin, leading to glomerular dysfunction. However, the relationships between these two processes in human diabetic nephropathy remain an open question. Since Psammomys obesus is an ideal animal model to study diabetes mellitus temporal evolution, we have used this model to study the correlation between kidney structural changes and modification on the expression levels of NFκB and E-cadherin over time. We have demonstrated that, after induction of diabetes metillus with a high energy diet (HED), P. obesus develops the characteristic symptoms of human disease. In detail, at the third month nuclear factor NFκB is expressed in the kidney of diabetic P. obesus and structural renal changes, such as mesangial expansion or interstitial fibrosis, are detectable; at 6 months, thickening of glomerular basement membrane, glomerular sclerosis, and tubular atrophy occurs; at 9 months, symptoms of the final stages of the disease, such as down expression of E-cadherin, happens. As a result of these observations we proposed that NFκB activation and E-cadherin down-expression are interlinked on diabetic kidney disease (DKD).