【摘要】 目的观察血管紧张素Ⅱ受体拮抗剂缬沙坦和盐皮质激素受体拮抗剂螺内酯对自发性高血压大鼠(spontane-ously hypertensive rats,SHR)心肌中活化的丝裂原活化蛋白激酶家族(m itogen-activated protein kinase fam ily,MAPK)(细胞外信号调节激酶[ERK]、c-Jun NH2-末端激酶[JNK]和p38)的影响。方法将18只雄性SHR随机分为3组,每组6只。其中两组分别用缬沙坦30 mg.kg-1.d-1、螺内酯20 mg.kg-1.d-1溶于饮水灌胃,连续治疗13周;对照组给正常饮水,并与W istar-kyoto大鼠(WKY)比较。用W estern-blot方法检测大鼠心肌磷酸化MAPK的表达。结果SHR对照组心肌磷酸化JNK/actin值高于其余3组(P<0.01),缬沙坦组高于螺内酯组和WKY组(P<0.01),螺内酯组与WKY水平接近;SHR对照组心肌磷酸化ERK/actin值高于其余3组(P<0.01),螺内酯和缬沙坦组高于WKY组(P<0.01),两用药组之间无差异;缬沙坦组磷酸化p38/actin值高于WKY组(P<0.01),低于SHR对照组和螺内酯组(P<0.01)。结论醛固酮能促进SHR的心肌肥厚和心肌纤维化,盐皮质激素受体拮抗剂能通过抑制MAPK途径而抑制左室肥厚和心肌纤维化。更多还原

【Abstract】 Objective To investigate the the role of spironolactone and valsartan in the expression of the dually phosphorylated active forms of mitogen-activated protein kinase family（MAPKs） [the extracellular signal-regulated kinase（ERK）,c-Jun NH₂-terminal kinase（JNK）,p38] in myocardium of spontaneously hypertensive rats（SHR）.Methods Six-week male SHRs were ramdomly assigned to administrate Spironolactone at dose of 20 mg·kg^-1·d^-1,or Valsartan of 30 mg·kg^-1·d^-1 or saline water that served as positive control（n=6 in each group） for 13 weeks.Six Wistar Kyoto rats（WKY） were used as normal control. Phosphorylation of MAPKs were assessed by Western blotting with phosphospecific antibodies.Results The ratio of phospho-JNK/actin in SHR control group was the highest among all groups（P<0.01）,and that of valsartan group was higher than that of spironolactone group and WKY group（P<0.01）.There was no significant difference between spironolactone group and WKY group（P>0.05）.The ratio of phospho-ERK/actin in valsartan group and spironolactone group was lower than that in SHR control group（P<0.01）,but higher than that in WKY group（P<0.01）.The difference between valsartan group and spironolactone group was not remarkable（P>0.05）.The ratio of phospho-p38/actin in spironolactone group was similar to that in SHR control group（P>0.05）,and that in valsartan group was higher than that in WKY group（P<0.01）,but lower than that in SHR control group and spironolactone group（P<0.01）.Conclusion These findings show that aldosterone promotes hypertrophy,cardiac remodeling and fibrosis,independent of blood pressure.Mineralocorticoid receptor blockade attenuates phosphorylation of MAPK and ameliorates cardiac remodeling in SHR.更多还原