Simvastatin reverses podocyte injury but not mesangial expansion in early stage type 2 diabetes mellitus.
Simvastatin reverses podocyte injury but not mesangial expansion in early stage type 2 diabetes mellitus.
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DOI：
10.1080/08860220902963848
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发表时间：
2009
期刊：
影响因子：
3
通讯作者：
Sansom SC
中科院分区：
文献类型：
--
作者：
Wei P;Grimm PR;Settles DC;Balwanz CR;Padanilam BJ;Sansom SC
他汀类药物可以在多种肾小球疾病中提供肾脏保护，包括糖尿病肾病（DN）。然而，不同的肾小球病变有不同的病因，并且对他汀类药物可能有不同的反应。本研究旨在确定辛伐他汀 (SMV) 对早期 2 型糖尿病 (DM) 小鼠模型中肾小球病理学的不同影响，包括系膜扩张和足细胞损伤。通过喂食高脂肪饮食（HF；45 kcal% 脂肪），在雄性 C57BL/6 小鼠中诱导 2 型糖尿病。 22周后，一组HF小鼠用SMV（HF-SMV；7μg/天/g BW）治疗，另一组通过微型渗透泵用载体（HF-载体）治疗4周。第三组作为年龄匹配的正常饮食载体对照（ND-载体；10 kcal% 脂肪）。治疗结束时，以盲法评估肾小球形态以确定 DN 的进展。心衰小鼠的体重、血糖、胰岛素、高密度脂蛋白胆固醇和甘油三酯增加，但低密度脂蛋白胆固醇没有增加。在治疗过程中，ND-载体的24小时尿白蛋白排泄量(UAE)没有变化。 HF 小鼠表现出UAE 升高，使用SMV 后UAE 降低，但使用媒介物后UAE 没有变化。绝对系膜体积和每肾小球体积的相对系膜体积在 HF 载体中增加，并且在 SMV 治疗后保持升高。去氧肾上腺素（足细胞裂隙隔膜完整性的蛋白质标志物）的免疫染色在 HF 载体中降低；然而，HF-SMV组的去氧肾上腺素数量与ND-载体没有差异。结论是，SMV 可逆转足细胞损伤，但不影响 2 型糖尿病早期蛋白尿肾脏中的系膜扩张。
Statins may confer renal protection in a variety of glomerular diseases, including diabetic nephropathy (DN). However, various glomerular lesions have different etiologies and may have different responses to statins. This study was performed to determine the differential effects of simvastatin (SMV) on glomerular pathology including mesangial expansion and podocyte injury in a mouse model of early stage type 2 diabetes mellitus (DM). Type 2 DM was induced in male C57BL/6 mice by feeding a high fat diet (HF; 45 kcal% fat). After 22 weeks, one group of HF mice was treated with SMV (HF-SMV; 7 μg/day/g BW) and another group was treated with vehicle (HF-vehicle) for 4 weeks via osmotic mini-pump. A third group served as age-matched normal diet vehicle controls (ND-vehicle; 10 kcal% fat). At the end of treatment, glomerular morphology was evaluated in a blind manner to determine the progression of DN. Body weight, blood glucose, insulin, HDL-cholesterol and triglycerides, but not LDL-cholesterol, were increased in HF mice. Over the course of treatment, the 24-hour urinary albumin excretion (UAE) was unchanged in ND-vehicle. HF mice exhibited elevated UAE, which decreased with SMV, but was unchanged with vehicle. The absolute mesangial volume and the relative mesangial volume per glomerular volume increased in HF-vehicle and remained elevated with SMV treatment. The immuno-staining of nephrin, a protein marker of the integrity of podocyte slit diaphragms, was decreased in HF-vehicle; however, the nephrin quantity of the HF-SMV group was not different from ND-vehicle. It is concluded that SMV reverses podocyte damage, but does not affect mesangial expansion in the kidneys of early stage proteinuria of type 2 DM.
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影响因子：
4
作者：
Cha, DR;Kang, YS;Kim, NH
通讯作者：
Kim, NH
影响因子：
4.8
作者：
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通讯作者：
Abboud, HE
DOI：
10.1152/ajprenal.00502.2005
发表时间：
2006-07-01
影响因子：
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作者：
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通讯作者：
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影响因子：
4.8
作者：
CONTI, FG;STRIKER, LJ;STRIKER, GE
通讯作者：
STRIKER, GE
DOI：
10.1097/01.asn.0000037401.02391.76
发表时间：
2003-01-01
影响因子：
13.6
作者：
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通讯作者：
Shimizu, F