PPARα agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

被引:80
作者
Hou, Xiaoyang [1 ,2 ,3 ]
Shen, Ying H. [3 ]
Li, Chuanbao [1 ,2 ]
Wang, Fei [1 ,2 ]
Zhang, Cheng [1 ,2 ]
Bu, Peili [1 ,2 ]
Zhang, Yun [1 ,2 ]
机构
[1] Shandong Univ, Qilu Hosp, Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Qilu Hosp, Chinese Minist Hlth, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Shandong, Peoples R China
[3] Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA
关键词
Peroxisome proliferator-activated receptor alpha; Hypertension; Renal fibrosis; Oxidative stress; Inflammation; MAPK; ACTIVATED RECEPTORS PPARS; RENAL DAMAGE; KINASE ACTIVATION; PROGRESSION; EXPRESSION; PRESSURE;
D O I
10.1016/j.bbrc.2010.03.043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidative stress has been shown to play an important role in the development of hypertensive renal injury Peroxisome proliferator-activated receptors alpha (PPAR alpha) has antioxidant effect. In this study, we demonstrated that fenofibrate significantly reduced proteinuria, inflammatory cell recruitment and extracellular matrix (ECM) proteins deposition in the kidney of SHRs without apparent effect on blood pressure To investigate the mechanisms involved, we found that fenofibrate treatment markedly reduced oxidative stress accompanied by reduced activity of renal NAD(P)H oxidase, increased activity of Cu/Zn SOD, and decreased phosphorylation of p38MAPK and JNK in the kidney of SHRs Taken together. fenofibrate treatment can protect against hypertensive renal injury without affecting blood pressure by inhibiting inflammation and fibrosis via suppression of oxidative stress and MAPK activity (C) 2010 Elsevier Inc All rights reserved.
引用
收藏
页码:653 / 659
页数:7
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