缬沙坦和螺内酯对高血压大鼠心肌c-Jun氨基末端激酶的影响

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(SHR)心肌中活化的丝裂原活化蛋白激酶家族(MAPK)中的c-Jun氨基末端激酶(JNK)的影响。方法将18只雄性SHR随机分为三组,每组6只。其中两组分别用缬沙坦30 mg.kg-1.d-1、螺内酯20mg.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Wistar-Kyoto大鼠(WKY)比较。用Western-blot方法检测大鼠心肌磷酸化JNK的表达。结果SHR对照组心肌磷酸化JNK/actin值高于其余三组(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。两治疗组的LVW/BW较SHR对照组明显减低(均P<0.01),但较WKY对照组有所升高(P<0.05,P<0.01)。两治疗组胶原容积分数(CVF)低于SHR对照组(均P<0.01),高于WKY组(均P<0.05)。结论缬沙坦和螺内酯均能通过抑制心肌中活化的JNK蛋白表达而抑制SHR的左室肥厚和心肌纤维化。

Effect of spironolactone and valsartan on the expressin of c-Jun NH2-terminal kinases in myocardium of spontaneously hypertensive rats

Objective To investigate the role of spironolactone and valsartan in the expression of the dually phosphorylated active forms of mitogen-activated protein kinase family（MAPKs） [c-Jun NH2-terminal kinase（JNK）] in myocardium of spontaneously hypertensive rats（SHR）.Methods Eighteen male SHR were divided into three groups at random：Spironolactone 20 mg·kg^-1·d^-1,Valsartan 30 mg·kg^-1·d^-1 were administered to rats in spironolactone group and valsartan group.SHR control group and Wistar Kyoto（WKY） group were given normal water during the same time.Phosphorylation of JNK was assessed by western blots with phosphospecific antibodies.Results After 13-week treatment,the rate of phospho-JNK/actin in hearts in SHR control group was the highest among all the groups（P〈0.01）,and the rate in valsartan group was higher than that in spironolactone group and WKY group（P〈0.01）.There was no significant difference between spironolactone group and WKY group（P〉0.05）.Conclusion These findings show that Valsartan and spironolacton can inhibit cardiac hypertrophy and fibrosis in SHR by attenuating phosphorylation of JNK.