Casey R G, Joyce M, Roche-Nagle G, Chen G, Bouchier-Hayes D
Department of Surgical Research, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
J Surg Res. 2005 Feb;123(2):176-81. doi: 10.1016/j.jss.2004.08.001.
Development of diabetes causes early functional (endothelial dysfunction) and morphological abnormalities in the kidney. If left untreated, these will ultimately progress to renal failure. Apart from strategies aimed at maintaining very tight glycemic control, attention has turned to the development of adjuvant therapy to maintain endothelial function in these patients. The agents receiving the most critical appraisal due to their endothelial protective effects are the 3-hydrox 3-methylglutaryl (HMG)-Co-enzyme A (CoA) reductase inhibitors. The aim of the study was to investigate: (1) the early alterations in the renal diabetic injury; and (2) to examine the protective role of Pravastatin in this end-organ diabetic model.
Sprague Dawley rats (n = 21) were randomized into three groups: (1) control; (2) diabetic; and (3) diabetic treated with Pravastatin. Diabetic nephropathy was investigated with serum biochemical parameters (urea, creatinine), functional parameters (total urinary protein loss, glomerular filtration rate, renal cortical blood flow), and structural assessment (hemotoxylin and eosin staining).
We demonstrated impairment in functional, biochemical, and structural parameters in the diabetic nephropathy group, which was diminished by treatment with Pravastatin. This was attributed to an up-regulation in endothelial constitutive nitric oxide synthase (ecNOS) expression in the treated diabetic group.
We have shown that Pravastatin, in an experimental model of early diabetes nephropathy preserves microvascular endothelial function in the presence of hyperglycemia, thus inhibiting the early stage of diabetic microangiopathy.
糖尿病的发展会导致肾脏早期出现功能性（内皮功能障碍）和形态学异常。若不加以治疗，这些异常最终会发展为肾衰竭。除了旨在维持严格血糖控制的策略外，人们已将注意力转向开发辅助治疗方法，以维持这些患者的内皮功能。因其内皮保护作用而受到最严格评估的药物是3-羟基-3-甲基戊二酰（HMG）-辅酶A（CoA）还原酶抑制剂。本研究的目的是调查：（1）糖尿病肾损伤的早期改变；（2）检验普伐他汀在这种终末器官糖尿病模型中的保护作用。
将21只Sprague Dawley大鼠随机分为三组：（1）对照组；（2）糖尿病组；（3）糖尿病普伐他汀治疗组。通过血清生化参数（尿素、肌酐）、功能参数（总尿蛋白丢失、肾小球滤过率、肾皮质血流量）和结构评估（苏木精和伊红染色）来研究糖尿病肾病。
我们证明糖尿病肾病组的功能、生化和结构参数出现损伤，而普伐他汀治疗可减轻这些损伤。这归因于治疗后的糖尿病组内皮型一氧化氮合酶（ecNOS）表达上调。
我们已表明，在早期糖尿病肾病的实验模型中，普伐他汀在高血糖情况下可保留微血管内皮功能，从而抑制糖尿病微血管病变的早期阶段。
