Folic acid attenuates hyperhomocysteinemia-induced glomerular damage in rats
Folic acid attenuates hyperhomocysteinemia-induced glomerular damage in rats
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DOI：
10.1016/j.mvr.2013.07.002
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发表时间：
2013-09-01
影响因子：
3.1
通讯作者：
Tan, Hongmei
中科院分区：
文献类型：
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作者：
Cao, Lu;Lou, Xiaoying;Tan, Hongmei
本研究旨在探讨叶酸（FA）降低血浆同型半胱氨酸（Hcy）水平是否能减轻高同型半胱氨酸血症（HHcy）相关的肾小球损伤及其可能机制。采用L-蛋氨酸灌胃法建立大鼠高同型半胱氨酸动物模型。FA也被灌胃给药。测定血浆Hcy、肌酐和尿白蛋白。光镜和电镜观察组织学和超微结构变化。采用免疫组化和Western blot方法检测肾组织中α-平滑肌肌动蛋白（α-SMA）、增殖细胞核抗原（PCNA）和转化生长因子β 1（TGF-β 1）的表达。L-蛋氨酸诱发大鼠高同型半胱氨酸。HHcy大鼠出现肾小球硬化和纤维化。血浆肌酐浓度和尿白蛋白排泄量也明显增加。HHCy大鼠足细胞足突消失并广泛融合，这与HHCy大鼠肾皮质nephrin蛋白表达减少有关。补充FA可显著降低血浆Hcy水平。血浆肌酐浓度和尿白蛋白排泄也显着衰减FA。形态学上，HHcy相关的肾小球硬化，纤维化，足细胞足突消失和足细胞nephrin的损失，显着改善FA。HHcy大鼠肾皮质α-SMA、PCNA和TGF-β 1表达增加，FA可部分逆转上述变化。提示血浆Hcy水平升高是肾小球损伤的重要致病因素。FA降低血浆Hcy水平可抑制TGF-β 1的表达，减轻Hcy对肾小球的损伤。(C)2013 Elsevier Inc. All rights reserved.
The present study investigated whether lowering plasma homocysteine (Hcy) with folic acid (FA) could attenuate hyperhomocysteinemia (HHcy)-associated glomerular damage and possible mechanisms. The HHcy animal model was established by intragastric administration with L-methionine in rats. FA was also given intragastrically. Plasma Hcy and creatinine and urinary albumin were measured. Histological and ultrastructural changes were observed by light and electron microscopes. The expression of alpha-smooth muscle actin (alpha-SMA), proliferating cell nuclear antigen (PCNA) and transforming growth factor-betal (TGF-beta 1) in the kidney was examined by immunohistochemical staining and western blot analysis. The administration of L-methionine induced HHcy in rats. The HHcy rats developed glomerulosclerosis and fibrosis. Plasma creatinine concentration and urinary albumin excretion were also significantly increased in HHcy rats. Effacement and extensively fusion of podocyte foot process was observed in HHcy rats, which was associated with decreased expression of nephrin protein in renal cortex of HHcy rats. Supplementation with FA lowered plasma Hcy significantly. Plasma creatinine concentration and urinary albumin excretion were also significantly attenuated by FA. Morphologically, HHcy-associated glomerulosclerosis, fibrosis, podocyte foot process effacement and loss of podocyte nephrin, were significantly improved by FA. The expressions of alpha-SMA, PCNA and TGF-beta 1 were increased in renal cortex of HHcy rats, and which were also partially reversed by FA. These data suggest that elevated plasma Hcy is an important pathogenic factor for glomerular damage. Lowering plasma Hcy by FA can inhibit TGF-beta 1 expression and attenuate HHcy-induced glomerular damage. (C) 2013 Elsevier Inc. All rights reserved.