论文部分内容阅读
目的研究两肾一夹高血压大鼠心肌肥厚过程中钙调神经磷酸酶(CaN)和丝裂原活化蛋白激酶(MAPK,包括胞外信号调节激酶、cJunNH2末端激酶、p38丝裂原活化蛋白激酶)的变化,探讨血管紧张素转换酶抑制剂培哚普利对心肌肥厚和CaN、MAPK的影响。方法制作两肾一夹高血压大鼠模型;以左心室重、左心室重与体重比值、心肌细胞横截面积、左心室后壁和室间隔厚度作为大鼠心肌肥厚指标;应用RTPCR法测定大鼠心肌CaN和MAPKmRNA表达,采用免疫印迹法检测CaN蛋白表达,以对硝基苯磷酸作底物测定CaN活性。结果两肾一夹术后2个月大鼠已发生心肌肥厚,术后3个月心肌肥厚进一步加重;手术组大鼠左心室心肌CaNmRNA、蛋白表达和CaN活性以及cJunNH2末端激酶mRNA表达均高于同龄假手术组。培哚普利治疗可逆转大鼠心肌肥厚和CaN、cJunNH2末端激酶的变化。结论培哚普利可通过抑制胞内CaN和cJunNH2末端激酶信号通路逆转两肾一夹高血压大鼠心肌肥厚。
Objective To study the effects of calcineurin (CaN) and mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase, cJunNH2 terminal kinase, p38 mitogen activated protein kinase ), To investigate the effect of angiotensin converting enzyme inhibitor perindopril on cardiac hypertrophy and CaN, MAPK. Methods Two-kidney-one-clip hypertensive rat models were established. Left ventricular mass, left ventricular mass and body weight ratio, myocardial cell cross-sectional area, left ventricular posterior wall and interventricular septum thickness were used as indexes of myocardial hypertrophy. Rat RTPCR The expressions of CaN and MAPK mRNA in myocardium were detected by Western blotting. The expression of CaN protein was detected by Western blotting. The activity of CaN was determined by using p-nitrophenylphosphate as substrate. Results Myocardial hypertrophy occurred 2 months after the two-kidney one-clip surgery in rats, and myocardial hypertrophy was further aggravated at 3 months after operation. CaN mRNA, protein expression, CaN activity and cJunNH2 terminal kinase mRNA expression in left ventricular myocardium were significantly increased in the operation group Same-age sham operation group. Perindopril treatment can reverse the changes of myocardial hypertrophy and CaN, cJunNH2 terminal kinase in rats. Conclusion Perindopril could reverse myocardial hypertrophy in two-kidney and one-clip hypertensive rats by inhibiting intracellular CaN and cJunNH2 terminal kinase signaling pathway.