| 摘要: |
| 目的探讨阿托伐他汀不依赖降血脂的肾脏保护作用的可能机制。方法雄性C57BL小鼠给予普通饮食作为对照组,CD36/SR-A/ApoE三敲小鼠随机分为高脂组和治疗组(高脂+阿托伐他汀)。实验满14周后处死取标本。采用酶法检测血清脂质水平；油红“O”染色检测肾组织内脂质沉积情况,H-E、PAS、Masson染色观察肾脏形态学改变；定量PCR技术与免疫组化检测肾组织转化生长因子(TGF-β)、纤维连接蛋白(fibronectin)、Ⅰ型胶原、Ⅳ型胶原、α肌动蛋白(α-SMA)表达。结果阿托伐他汀能够减少三敲小鼠肾脏组织脂质沉积,但血清中的脂质水平无明显降低。阿托伐他汀可以减少高脂饮食诱导的肾脏组织系膜细胞的增生、系膜基质的沉积,肾小管间质炎症细胞的浸润、肾小管的变性扩张,细胞外基质的沉积。阿托伐他汀不但可以明显降低肾脏组织TGF-β的基因与蛋白表达,还降低纤维化相关因子的基因与蛋白表达。结论阿托伐他汀可不依赖降血脂,独立于SR-A、CD36受体途径而发挥肾脏保护作用；这种作用可能是通过降低TGF-β的表达而实现的。 |
| 关键词: 阿托伐他汀；高脂血症；肾小球硬化症；转化生长因子β A类清道夫受体； CD36抗原 |
| DOI：10.3724/SP.J.1008.2010.0734 |
| 投稿时间：2010-03-12修订日期：2010-04-29 |
| 基金项目:国家自然科学基金(30871159,30971389,30772295,30530360), 重庆市自然科学基金重点项目(2008BA5016, 2009BA5080, 2009-1-34). |
|
| Reno-protective effects of atorvastatin independent of blood cholesterol lowering |
| XU Zhen-e1, YAN Feng2, RUAN Xiong-zhong2, CHEN Ya-xi 2*, LI Qiu1*,LI Qiu，CHEN Ya-xi |
| (1.Department of Nephrology, Children’s Hospital, Chongqing Medical University, Chongqing 400014, China; 2.Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing 400016, China) |
| Abstract: |
| ObjectiveTo investigate whether atorvastatin can prevent renal injury in mice independent of the lipid-lowering effects.MethodsCD36-/-SR-A-/-ApoE-/-mice were randomly assigned to a high fat diet (high fat group) and high fat diet plus atorvastatin (atorvastatin) group; male C57BL mice with a chow diet served as controls.Terminal blood samples were taken for plasma cholesterol assay 14 weeks later.Renal sections were used for histological and immunohistochemistry assessments.The lipid accumulation in the kidney was evaluated by Oil Red O (ORO) staining.The mRNA expression of transforming growth factor-β (TGF-β), collagen Ⅰ and Ⅳ, fibronectin, and α-smooth muscle actin (α-SMA) were analyzed by real-time PCR.ResultsBlood total cholesterol levels (LDL-cholesterol and HDL-cholesterol) were not significantly different between atorvastatin group and high fat group.Meanwhile, ORO staining showed that atorvastatin decreased lipid accumulation in the kidney; Masson and H-E staining demonstrated that atorvastatin therapy attenuated massive structural changes, including mesangial proliferation, interstitial matrix deposition, accumulation of extracellular matrix proteins, tubular-interstitial inflammatory cell infiltration, and renal deformations with glomerulosclerosis/tubulointerstitial fibrosis in the high fat group.Moreover, atorvastatin therapy not only decreased TGF-β expression at mRNA and protein levels, but also decreased the expression of factors related to fibrosis.ConclusionAtorvastatin can protect the kidney independent of the lipid-lowering effects and SR-A,CD36 receptor pathways, and it might be related to decrease of TGF-beta expression. |
| Key words: atorvastatin hyperlipidemias glomerulosclerosis transforming growth factor beta class A scavenger receptors CD36 antigens |
