Lipid accumulation and transforming growth factor-β upregulation in the kidneys of rats administered angiotensin II

Lipid accumulation and transforming growth factor-β upregulation in the kidneys of rats administered angiotensin II
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DOI:
10.1161/01.hyp.0000184653.75036.d5
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发表时间:
2005-11-01
期刊:
影响因子:
8.3
通讯作者:
Nagai, R
Nagai, R
中科院分区:
医学1区
文献类型:
--
作者:
Saito, K;Ishizaka, N;Nagai, R

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脂质代谢异常可能在进行性肾衰竭中起作用。我们研究了血管紧张素ii注入动物肾脏中是否发生脂质积累以及脂质沉积是否与转化生长因子- β 1 (tgf - β 1)共定位。油红0染色显示血管紧张素ii处理的大鼠小管上皮细胞和血管壁细胞有明显的脂质沉积,而去甲肾上腺素处理的大鼠则没有。组织学分析显示,血管紧张素ii输注动物的脂质阳性小管上皮细胞中超氧化物含量增加,tgf - β 1 mRNA表达增强。血管紧张素ii处理大鼠肾脏中固醇调节元件结合蛋白I (SREBP-1)和脂肪酸合酶mRNA的表达分别约为对照组的3倍和1.5倍。用铁螯合剂去铁胺治疗血管紧张素ii注入的动物,减轻了血管紧张素ii诱导的肾中SREBP-1和脂肪酸合成酶表达的增加,并使肾皮质组织中的脂质含量正常化。脂质代谢异常可能与血管紧张素ii注入动物肾脏中tgf - β 1 I表达上调和铁稳态异常有关。
Abnormal lipid metabolism may play a role in progressive renal failure. We studied whether lipid accumulation occurs and whether lipid deposits are colocalized with transforming growth factor-beta 1 (TGF-beta 1) in the kidney of angiotensin II-infused animals. Oil red 0 staining showed marked lipid deposition in the tubular epithelial and vascular wall cells of angiotensin II-treated but not in norepinephrine-treated rats. Histological analyses showed that increased amounts of superoxide and intense TGF-beta 1 mRNA expression were present in lipid-positive tubular epithelial cells in angiotensin II-infused animals. Protein expression of sterol regulatory element-binding protein I (SREBP-1) and mRNA expression of fatty acid synthase in the kidney were approximate to 3 times and 1.5 times, respectively, higher in angiotensin II-treated rats than in controls. Treatment of angiotensin II-infused animals with an iron chelator, deferoxamine, attenuated the angiotensin II-induced increases in renal expression of SREBP-1 and fatty acid synthase and normalized the lipid content in the renal cortical tissues. Abnormal lipid metabolism may be associated with upregulation of TGF-beta 1 I expression and aberrant iron homeostasis in the kidneys of angiotensin II-infused animals.