组织醛固酮对白发性高血压大鼠心脏靶器官的损害和伊普利酮的保护作用

目的观察自发性高血压大鼠（Spontaneously hypertensive rats,SHR）中醛固酮和心室重构与心肌细胞凋亡的关系以及选择性盐皮质激素受体拮抗剂——依普利酮（Eplerenone，Epl）对心室重构和心肌细胞凋亡的抑制作用。方法20只8周龄雄性SHR随机分为2组，SHR—Epl组（Epl50mg／Kg）和SHR—C组（高血压对照组），10只雄性WistarKyoto大鼠（WKY）作为正常血压对照组。用放射免疫方法检测血浆和心肌组织醛固酮浓度；通过检测天狼星红染色组织切片的胶原蛋白沉积分数来评价心肌纤维化；应用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL）检测心肌细胞凋亡；应用RT—PCR和Western—Blotting法检测Bel-2和BaxmRNA和蛋白表达。结果SHR—Epl组和SHR—C组较WKY组收缩压升高（P〈0．01），但此两组间无差别。SHR—Ep1组、SHR—C组和WKY组的心重／体重分别是（3．48±0．56），（4．04±0．27）和（2．78±0．12）mg／g；心肌细胞直径是（15．15±0．14），（17．24±0．36）和（14．31±0．20）Ixm；胶原蛋白沉积分数是（3．81±0．30），（4．39±0．23）和（3．48±0．23）％；凋亡指数是（0．36±0．21），（1．95±0．17）和（0．21±0．05）％，SHR—C组均高于WKY组（P〈0．01）和SHR—Epl组（P〈005），且SHR—Epl组高于WKY组（P〈0．05）。SHR—Epl组的Bcl-2／baxmRNA和蛋白表达比值高于SHR—C组（P〈0．05）。结论SHR心肌组织可以分泌醛固酮，且在心室重构和心肌细胞凋亡过程中起到重要的促进作用，Epl对SHR心室重构和心肌细胞凋亡有一定抑制作用。

Damage of Aldosterone on the Heart of the Rat with Spontaneously Hypertensive and Protective Effect of Eplerenone

Objective To observe the relationship between aldosterone in tissue and blood plasma and cardiomyocyte apoptosis in spontaneously hypertensive rats （SHR）, and the effect of Eplerenone （Epl） on ventricular remodeling and apoptosis. Methods Twenty 8-week-old male SHR were randomly divided into two groups： SHR-Epl （treated with Epl, 50 mg/kg） and SHR-C （placebo）. Ten male Wistar Kyoto rats （WKY） treated with placebo acted as the normotensive control. Aldosterone concentration of plasma and myocardial tissue were detected by radioimmunoassay. LV fibrosis was assessed by determination of collagen density （picrosirius red staining） on tissues obtained from the cross sections. Cardiomyoeyte apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. Bcl-2/bax mRNA and protein expression were examined by RT-PCR and Western Blotting. Results Systolic BP was increased significantly in both SHR-Epl and SHR-C group compared with WKY group （P〈0.01）, but no difference between SHR-Epl and SHR-C group （P〉0.05）. HW/BW （mg/g） of SHR-Epl, SHR-C and WKY group was 3.48±0.56, 4.04±0.27 and 2.78±0.12, respectively; Cardiomyocyte diameter （μm） were 15,15±0.14, 17.24±0.36 and 14.31±0.20; The collagen volume fraction （%） were 3.81_±0.30, 4.39±0.23 and 3.48±0.23; and the apoptotic index were 0.36±0.21, 1.95±0.17 and 0.21±0.05 respectively. SHR-C group were all increased than WKY group （P〈0.01） and than SHR-Epl group （P〈005）, then SHR-Epl group were higher compared with WKY group （P〈0.05）. The ratio of Bcl-2/bax mRNA and protein expression of SHR-Epl group was higher than SHR-C group （P〈0.05）. Conclusion Heart can produce aldosterone. Tissue aldosterone plays an important role in ventricular remodeling and cardiomyocyte apoptosis in SHR. Epl can attenuate the action of aldosterone and suppress the ventricular remodeling and heart apoptosis of SHR.