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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Wistar Kyoto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Bcl-2和Bax mRNA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-Epl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)μm;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/bax mRNA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。
Objective To observe the relationship between aldosterone and ventricular remodeling and cardiomyocyte apoptosis in spontaneously hypertensive rats (SHR) and the effect of selective mineralocorticoid receptor antagonist Eplerenone (Epl) Ventricular remodeling and cardiomyocyte apoptosis. Methods Twenty male SHR were randomly divided into 2 groups: SHR-Epl group (Epl50mg / Kg) and SHR-C group (control group) and 10 male Wistar Kyoto rats (WKY) . Plasma and cardiac aldosterone concentrations were measured by radioimmunoassay. Myocardial fibrosis was evaluated by detecting the collagen deposition of Sirius red stained sections. Deoxyribonucleotide end-transferase-mediated nick end labeling (TUNEL) Cardiomyocytes apoptosis was observed. The mRNA and protein expressions of Bcl-2 and Bax were detected by RT-PCR and Western-blotting. Results Compared with WKY group, systolic blood pressure increased in SHR-Epl group and SHR-C group (P <0.01), but there was no difference between the two groups. The cardiac weight / body weight of SHR-Epl group, SHR-C group and WKY group were (3.48 ± 0.56), (4.04 ± 0.27) and (2.78 ± 0.12) mg / g respectively; the diameter of cardiomyocytes was (15.15 ± 0.14) 17.24 ± 0.36 and 14.31 ± 0.20 μm, respectively. The collagen deposition scores were (3.81 ± 0.30), (4.39 ± 0.23) and (3.48 ± 0.23)%, respectively. The apoptotic indexes were (0.36 ± 0.21) and (1.95 ± 0.17 (P <0.01) and SHR-Epl group (P <0.01), and SHR-Epl group was higher than WKY group (P <0.05). The ratio of Bcl-2 / bax mRNA and protein expression in SHR-Epl group was higher than that in SHR-C group (P <0.05). Conclusions SHR can secrete aldosterone and play an important role in ventricular remodeling and cardiomyocyte apoptosis. Epl can inhibit ventricular remodeling and cardiomyocyte apoptosis in SHR.