[过氧化物酶体增殖物激活受体α激动剂非诺贝特使自发性高血压大鼠左心室肥厚消退并增加心肌过氧化物酶体增殖物激活受体α表达]

[PPAR alpha activator fenofibrate regressed left ventricular hypertrophy and increased myocardium PPAR alpha expression in spontaneously hypertensive rats].

作者信息

Chen Hong-juan, Chen Jun-zhu, Wang Xing-xiang, Yu Min

机构信息

The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007 Sep;36(5):470-6. doi: 10.3785/j.issn.1008-9292.2007.05.011.

DOI:10.3785/j.issn.1008-9292.2007.05.011

PMID:17924466

Abstract

OBJECTIVE

To investigate the effect of PPAR alpha activator fenofibrate on left ventricular hypertrophy and myocardium PPAR alpha (peroxisome proliferator-activated receptor-alpha) expression in spontaneously hypertensive rats (SHR).

METHODS

Sixteen nine-week-old male spontaneously hypertensive rats were randomly divided into two groups: SHR received fenofibrate 100 mg x kg(-1) x d(-1) by oral gavage once daily for 8 weeks (SHR-F, n=8), and SHR received vechile (0.9 % saline) acted as controls (SHR, n=8). Age-matched Wistar-kyoto rats received vehicle for 8 weeks were served as negative controls (WKY, n=8). Systolic blood pressure was measured at the beginning, 2, 4, and 8 weeks of the experiment. At the end of the experiment, plasma BNP (brain natriuretic peptide)and lipid levels were measured. Left ventricular hypertrophy was accessed by pathological analysis. The expression of PPAR alpha and nuclear factor-kappa B (NF-kappa B p65) were investigated by the method of Western blotting.

RESULT

Compared with SHR group, systolic blood pressure was slightly lowered in SHR-F group, but it didn't reach significant level(p>0.05). Fenofibrate administration lowered plasma BNP in SHR-F group (P<0.01). There were not much difference of plasma lipid levels between SHR-F and SHR group. Left ventricular mass index (assessed by left ventricular weight/body weight, g x kg(-1)), transdiameter of cardiomyocyte (TDM), cardiomyocyte area (CA), collagen volume fraction (CVF), and perivascular circumferential area (PVCA) decreased significantly in SHR-F group (P<0.05, P<0.01). The myocardium PPAR alpha expression increased significantly (P<0.01), and NF-kappa B p65 expression decreased significantly (P<0.01) in SHR-F group.

CONCLUSION

PPAR alpha activator fenofibrate can regress left ventricular hypertrophy and increase myocardium PPAR alpha expression in spontaneously hypertensive rats, which is perhaps independent of its lipid-lowering activity.

摘要

目的

研究过氧化物酶体增殖物激活受体α（PPARα）激动剂非诺贝特对自发性高血压大鼠（SHR）左心室肥厚及心肌PPARα表达的影响。

方法

将16只9周龄雄性自发性高血压大鼠随机分为两组：SHR组给予非诺贝特100 mg·kg⁻¹·d⁻¹，每日经口灌胃1次，共8周（SHR-F组，n = 8）；SHR组给予溶媒（0.9%生理盐水）作为对照（SHR组，n = 8）。将年龄匹配的Wistar-kyoto大鼠给予溶媒8周作为阴性对照（WKY组，n = 8）。在实验开始时、第2、4和8周测量收缩压。实验结束时，检测血浆脑钠肽（BNP）和血脂水平。通过病理分析评估左心室肥厚情况。采用蛋白质印迹法检测PPARα和核因子κB（NF-κB p65）的表达。

结果

与SHR组相比，SHR-F组收缩压略有降低，但未达到显著水平（p>0.05）。非诺贝特给药降低了SHR-F组的血浆BNP水平（P<0.01）。SHR-F组与SHR组血脂水平差异不大。SHR-F组左心室质量指数（以左心室重量/体重，g·kg⁻¹评估）、心肌细胞横径（TDM）、心肌细胞面积（CA）、胶原容积分数（CVF）和血管周围周径面积（PVCA）均显著降低（P<0.05，P<0.01）。SHR-F组心肌PPARα表达显著增加（P<0.01），NF-κB p65表达显著降低（P<0.01）。