Katzir Ze'ev, Leibovitch Elena, Vaknin Hanan, Schreiber Letizia, Berger Esther, Matas Zipora, Fux Asora, Boaz Mona, Briliant Alexander, Biro Alexander
Institute of Nephorolgy, E. Wolfson Medical Center, Holon, Israel.
Clin Nephrol. 2013 Mar;79(3):214-20. doi: 10.5414/CN107621.
IgA nephropathy (IgAN) is the most common chronic glomerulonephritis in humans and is a major cause of end-stage kidney disease worldwide. There is no agreement on the exact underlying mechanism or therapeutic intervention for this disorder. Mesangial proliferation typifies the renal histopathology in IgAN. Statin drugs, as prenylationinhibitors, have been shown to have an antiproliferative effect on renal mesangial cells and to reduce IgAN-associated glomerulusclerosis and proteinuria. The aim of this study is to examine the effect of atorvastatin on kidney function, proteinuria and kidney histology changes in IgANinduced rats.
IgAN was induced in Wistar-Kyoto rats by bovine γ-globulin (BGG). Four groups of rats were treated in metabolic cages: 1) control; 2) atorvastatin (2 mg/kg body weight/day through nasogastric tube) - treated rats; 3) IgAN-rats; 4) IgAN-rats treated with atorvastatin. Urine volume, urine protein excretion, blood urea and creatinine concentrations in addition to creatinine clearance were examined every 14 days, throughout the duration of the study (56 days). All kidneys from sacrificed rats were examined for histology including glomerular cell nuclei count and immunofluorescence.
There were no differences in blood creatinine concentrations between the groups. Creatinine clearance was lower on the 42nd day and proteinuria was higher on Days 14, 42 and 56, in rats in Group 3 compared to all others; additionally, histology examination revealed a higher glomerular cell nuclei count in this group. Immunofluorescence was equally positive for IgA in mesangial cells in the kidneys from rats of Groups 2, 3 and 4.
Atorvastatin attenuates kidney-function impairment, proteinuria and mesangial cell proliferation in BGG model of IgANinduced rats.
IgA 肾病（IgAN）是人类最常见的慢性肾小球肾炎，也是全球终末期肾病的主要病因。对于这种疾病的确切潜在机制或治疗干预尚无共识。系膜增生是 IgA 肾病肾脏组织病理学的典型特征。他汀类药物作为异戊二烯化抑制剂，已被证明对肾系膜细胞具有抗增殖作用，并可减少 IgA 肾病相关肾小球硬化和蛋白尿。本研究的目的是探讨阿托伐他汀对 IgA 诱导大鼠的肾功能、蛋白尿和肾脏组织学变化的影响。
通过牛γ球蛋白（BGG）在 Wistar-Kyoto 大鼠中诱导 IgA 肾病。四组大鼠在代谢笼中接受治疗：1）对照组；2）阿托伐他汀（通过鼻胃管给予 2mg/kg 体重/天）治疗的大鼠；3）IgA 肾病大鼠；4）用阿托伐他汀治疗的 IgA 肾病大鼠。在整个研究期间（56 天），每 14 天检测尿量、尿蛋白排泄、血尿素和肌酐浓度以及肌酐清除率。对处死大鼠的所有肾脏进行组织学检查，包括肾小球细胞核计数和免疫荧光检查。
各组间血肌酐浓度无差异。与其他所有组相比，第 3 组大鼠在第 42 天肌酐清除率较低，在第 14、42 和 56 天蛋白尿较高；此外，组织学检查显示该组肾小球细胞核计数较高。第 2、3 和 4 组大鼠肾脏系膜细胞中 IgA 的免疫荧光同样呈阳性。
阿托伐他汀可减轻 IgA 诱导大鼠的 BGG 模型中的肾功能损害、蛋白尿和系膜细胞增殖。
