依普利酮改善自发性高血压大鼠血管重构与降压无关

Effects of Eplerenone on Vascular Remodeling in Spontaneously Hypertensive Rats not Related with Blood Pressure

背景目前研究结果表明依普利酮降低血压的同时可以降低心肌小动脉的中层厚与腔径的比值及主动脉的中层面积,减少纤维堆积,改善血管重构,但依普利酮对血管重构的影响是否独立于降压之外尚无定论。目的观察自发性高血压大鼠(SHR)血管重构,醛固酮及其受体拮抗剂依普利酮对血管重构的影响。方法选择8周龄雄性SHR随机分为SHR组(n=10)和依普利酮组[50 mg/(kg.d),n=10],同龄雄性京都(WKY)大鼠作为对照组(n=10)。每周测量大鼠体质量,实验0、5及10周时测量血压。于0及10周时测血浆醛固酮。10周时取主动脉和颈动脉制成石蜡切片,天狼猩红染色并采用I mage-Pro Plus(IPP)图像分析系统测量中层厚度与腔径比值(MT/LD)、中层面积与腔面积比值(MA/LA),免疫组织化学法检测主动脉和颈动脉转化生长因子β1(TGF-β1)表达。结果实验10周时,依普利酮未能降低SHR收缩压(P>0.05)。10周时,依普利酮有降低SHR血浆醛固酮水平趋势(P>0.05)。依普利酮降低SHR主动脉的MT/LD、MA/LA及TGF-β1表达[MT/LD,依普利酮组(0.153±0.010)比SHR组(0.173±0.013);MA/LA,依普利酮组(0.333±0.034)比SHR组(0.370±0.031);TGF-β1表达,依普利酮组(0.030±0.008)比SHR组(0.044±0.014),均P<0.05]。同时依普利酮也能降低SHR颈动脉的MT/LD、MA/LA及TGF-β1表达(均P<0.05)。结论依普利酮在未降低血压的情况下,改善SHR主动脉和颈动脉以MT/LD、MA/LA增大和TGF-β1表达增高为特点的血管重构。

Background Several studies have shown beneficial effects of eplerenone in reduction of media to lumen ratio of intramyocardial arteries, media cross-sectional area of aorta, and attenuation of collagen deposition are concomitantly with lowering blood pressure. However, whether the effects of eplerenone on vascular remodeling are independent of lowering blood pressure are controversial. Objective To observe the effects of eplerenone on vascular remodeling in spontaneously hypertensive rats （SHR） in the absence of lowering BP. Methods Twenty SHR were randomly to receive plaeebo（n = 10） or eplerenone group （50 mg/kg per day, n = 10）, 10 Wistar-Kyoto （WKY） rats served as controls. Treatment began from 8th week old and last for 10 weeks. Blood pressure Was measured noninvasively every 5 weeks. Plasma aldosterone was measured. Aortic and carotid arteries were evalua- ted using Sirius red staining and image analysis. The ratio of media thickness/luminal diameter （MT/LD）, and media area/luminal area （MA/LA） , expression of transforming growth factor β1 （TGF-β1） of aortic and carotid artery were determined. Results 50 mg/kg dosage of eplerenone did not decrease the BP of SHR, but had the trend although not statistic significantly decreased plasma aldosterone （P〉0.05）. Eplerenone markedly decreased the MT/LD, MA/LA, and expression of TGF-β1 of aortic artery in SHR [MT/LD, eplerenone （0. 153±0. 010） vs placebo （0. 173±0. 013）; MA/LA, eplerenone （0. 333±0. 034） vs placebo （0.370±0. 031）; expression of TGF-β1, eplerenone： （0. 030±0. 008） vs placebo （0. 044±0. 014）, all P〈0.05-1, and also decreased the MT/LD, MA/LA, and expression of TGF-β1 of carotid artery significantly （all P〈0.05 ）. Conclusion Eplerenone prevented the progression of vascular remodeling without lowering effect on blood pressure.