Hohenstein Bernd, Hugo Christian P M, Hausknecht Birgit, Boehmer Kirsten P, Riess Regine H, Schmieder Roland E
Roland E. Schmieder, Department of Nephrology and Hypertension, University Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany. Tel: +49-9131-8536245; Fax: +49-9131-8539209; E-mail:
Nephrol Dial Transplant. 2008 Apr;23(4):1346-54. doi: 10.1093/ndt/gfm797. Epub 2007 Dec 9.
Changes of renal nitric oxide (NO) production have been associated with glomerular hyperfiltration, vascular permeability, albuminuria, glomerulosclerosis and tubulointerstitial fibrosis. Several studies demonstrated an up- as well as downregulated expression of NO-synthases (NOS) in experimental diabetic nephropathy. It is still not yet specified whether the regulation and activity of NOS is changed in human diabetic nephropathy.
Renal biopsies and clinical data of 45 patients with diabetic nephropathy and of 10 control subjects were investigated. Glomerular and cortical endothelial NOS (eNOS) and inducible NOS (iNOS) expression were assessed by immunohistochemical staining and related to clinical data such as the duration of diabetes, insulin therapy and arterial hypertension, albuminuria/proteinuria, eGFR according to the formula modification of diet in renal disease (MDRD), presence of vascular complications or diabetic retinopathy.
The mean age of patients at biopsy was 60.3 years and the mean duration of diabetes 12.9 years. Expression of cortical and glomerular eNOS was increased in type 2 diabetes (P < 0.05). Increased expression of glomerular and cortical eNOS correlated with more severe vascular complications (r = 0.44; P < 0.05). Glomerular eNOS was strongly increased among different degrees of proteinuria (P < 0.01). In contrast to expression levels of eNOS, the glomerular expression pattern of iNOS changed from an endothelial pattern in glomeruli with preserved morphology towards expression predominantly by inflammatory cells.
Thus, increased eNOS expression by the renal endothelium could be demonstrated in type 2 diabetic nephropathy, whereas iNOS was unchanged but spatially differentially expressed. The eNOS expression was related to vascular lesions and the degree of proteinuria.
肾脏一氧化氮（NO）生成的变化与肾小球高滤过、血管通透性、蛋白尿、肾小球硬化和肾小管间质纤维化有关。多项研究表明，在实验性糖尿病肾病中，一氧化氮合酶（NOS）的表达上调和下调。在人类糖尿病肾病中，NOS的调节和活性是否发生变化仍未明确。
对45例糖尿病肾病患者和10例对照者的肾活检及临床资料进行研究。通过免疫组织化学染色评估肾小球和皮质内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）的表达，并与糖尿病病程、胰岛素治疗、动脉高血压、蛋白尿/蛋白尿、根据肾病饮食改良公式（MDRD）计算的估算肾小球滤过率（eGFR）、血管并发症或糖尿病视网膜病变等临床资料相关联。
活检时患者的平均年龄为60.3岁，平均糖尿病病程为12.9年。2型糖尿病患者皮质和肾小球eNOS的表达增加（P < 0.05）。肾小球和皮质eNOS表达增加与更严重的血管并发症相关（r = 0.44；P < 0.05）。在不同程度的蛋白尿中，肾小球eNOS显著增加（P < 0.01）。与eNOS的表达水平相反，iNOS在肾小球中的表达模式从形态正常的肾小球中的内皮模式转变为主要由炎症细胞表达。
因此，在2型糖尿病肾病中可证明肾内皮细胞eNOS表达增加，而iNOS未发生变化，但在空间上存在差异表达。eNOS表达与血管病变和蛋白尿程度相关。
