Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.
Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.
复制标题
高脂血症会加重 B6.ROP Os/ 小鼠的肾脏疾病。
DOI：
10.1111/j.1523-1755.2004.00854.x
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Alpers,CharlesE
中科院分区：
文献类型：
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作者：
Muhlfeld,AnjaS;Spencer,MinW;Hudkins,KellyL;Kirk,Elizabeth;LeBoeuf,ReneeC;Alpers,CharlesE
B6.ROP Os/+小鼠的高血压性肾病。IntroductionReduction肾质量经常与肾功能的进行性丧失有关。方法采用高脂饮食（HFHC）和普通饲料喂养B6. ROP Os/+小鼠12周，观察高脂血症对B6. ROP Os/+小鼠肾脏病理和组织损伤介质的影响。肾功能和肾脏病理进行了assessed. ResultsHyperglycemia导致C57 BL/6小鼠肾功能下降。肾脏病理学特征为肾小球基质和细胞结构增加、肾小球和肾小管间质巨噬细胞内流以及肾小管上皮细胞更新增加。喂食饲料的B6.ROP Os/+动物表现出肾小球肥大，肾小球系膜基质和细胞结构增加，其特征在于巨噬细胞流入和增殖增加。肾小管上皮细胞显示巨噬细胞增加以及肾小管萎缩和扩张。肾脏病理伴有血尿素氮（BUN）和蛋白尿增加。与普通饲料喂养的B6.ROP Os/+动物相比，B6.ROP Os/+小鼠中的高血压导致血浆BUN增加，并通过进一步增加肾小球基质和肾小球细胞过多而加重肾脏病理学。肾小球细胞增多与血小板衍生生长因子-B（PDGF B）及其受体β表达增加相关。B6.ROP Os/+小鼠肾小球转化生长因子-β（TGF-β）mRNA表达增加，高脂血症C57 BL/6小鼠和高脂血症B6.ROP Os/+小鼠与对照组相比，与系膜基质的量相关。肾功能下降的小鼠至少部分通过细胞因子PDGF B和TGF-β的肾表达增加介导。
Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.IntroductionReduction of renal mass is frequently associated with progressive loss of kidney function. We examined the effects of hyperlipidemia on renal pathology and mediators of tissue damage in B6.ROP Os/+ mice, a model of reduced renal mass.MethodsC57BL/6 control mice and B6.ROP Os/+ mice were fed normal rodent chow or a high fat, high cholesterol (HFHC) diet for 12 weeks. Kidney function and renal pathology were assessed.ResultsHyperlipidemia led to a decline in kidney function in C57BL/6 mice. Renal pathology was characterized by an increase in glomerular matrix and cellularity, glomerular and tubulointerstitial macrophage influx, and increased tubular epithelial cell turnover. Chow-fed B6.ROP Os/+ animals demonstrated glomerular hypertrophy with an increase in mesangial matrix and cellularity that was characterized by macrophage influx and increased proliferation. The tubulointerstitium showed increased macrophages as well as tubular atrophy and dilation. Renal pathology was accompanied by an increase in blood urea nitrogen (BUN) and proteinuria. Hyperlipidemia in B6.ROP Os/+ mice resulted in increased plasma BUN compared to chow-fed B6.ROP Os/+ animals and aggravated renal pathology by further increasing glomerular matrix and glomerular hypercellularity. Glomerular hypercellularity was associated with increased expression of platelet-derived growth factor-B (PDGF B) and its receptor β. Glomerular transforming growth factor-β (TGF-β) mRNA expression was increased in B6.ROP Os/+ mice, hyperlipidemic C57BL/6 mice and hyperlipidemic B6.ROP Os/+ animals compared to controls and correlated with the amount of mesangial matrix.ConclusionThis study demonstrates that hyperlipidemia worsens renal pathology in B6.ROP Os/+ mice with a decline in renal function mediated at least in part through increased renal expression of the cytokines PDGF B and TGF-β.