摘要
目的:探讨PPARα(peroxisome proliferator-activated receptor-α)激动剂菲诺贝特(fenofibrate)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)左室肥厚及心肌PPARα表达的影响。方法:自发性高血压大鼠分两组(每组8只),非诺贝特治疗组(SHR-F)以非诺贝特100mg.kg-1.d-1灌胃;对照组(SHR)以生理盐水灌胃。同周龄Wistor-Kyoto鼠为阴性对照组(WKY,n=8),以生理盐水灌胃,共治疗8周。治疗前及治疗后2、4、8周测量大鼠尾动脉血压,治疗后测血浆脑型钠尿肽(brain natriuretic peptide,BNP)及血脂水平,以心脏组织病理分析判断心肌肥厚,Western blot检测心肌组织PPARα及核因子-κB p65亚单位(nuclear factor-kappa B,NF-κBp65)的表达水平。结果:经过8周治疗,SHR-F组尾动脉血压与SHR组相比略有降低,但无统计学意义(P>0.05)。SHR-F组与SHR组血脂水平无明显差异(P>0.05)。SHR-F组血浆BNP低于SHR组(P<0.01),与WKY组无明显差异。SHR-F组左室重量指数、心肌纤维化指标低于SHR组(P<0.05,P<0.01)。SHR-F组PPARα表达高于SHR组(P<0.01),NF-κB p65表达则低于SHR组(P<0.01)。结论:PPARα激动剂非诺贝特能改善自发性高血压大鼠左室肥厚及PPARα表达,其可能通过降脂以外的作用。
Objective： To investigate the effect of PPARα activator fenofibrate on left ventricular hypertrophy and myocardium PPARα （peroxisome proliferator-activated receptor-α） expression in spontaneously hypertensive rats （SHR）. Methods： Sixteen nine-week-old male spontaneously hypertensive rats were randomly divided into two groups ：SHR received fenofibrate 100mg · kg^-1 · 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 anaylsis. The expression of PPARα and nuclear factorkappa B （NF-κB p65） were investigated by the method of Western blotting. Results： 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 · 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 PPARα expression increased significantly （P 〈 0. 01 ）, and NF-κB p65 expression decreased significantly （P 〈 0. 01 ） in SHR-F group. Conclusion ： PPARα activator fenofibrate can regress left ventricular hypertrophy and increase myocardium PPARα expression in spontaneously hypertensive rats ,which is perhaps independent of its lipid-lowering activity.
出处
《浙江大学学报（医学版）》
CAS
CSCD
2007年第5期470-476,共7页
Journal of Zhejiang University(Medical Sciences)
基金
浙江省科技厅研究基金(021107613)
浙江省卫生科学研究基金(2003A043)
作者简介
陈红娟（1969-），女，博士，副主任医师，从事心血管内科基础及临床研究
通讯作者：陈君柱（1943-），男，教授，博士生导师，从事心血管内科基础及临床研究；Email：cch87019@163.com
