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目的 :观察心肌肥厚大鼠心肌肌浆网 ( sarcoplasmic reticulum,SR)和核被膜 ( nuclear envelope,NE)的 ryanodine受体 ( Ry R)的变化 ,进一步探讨心肌肥厚发生机制。方法 :采用腹主动脉缩窄术制作心肌肥厚模型。用差速离心和密度梯度离心法分离心肌 SR和 NE,用同位素标记配体研究 Ry R的动力学特征。结果 :心肌细胞 NE上也存在 Ry R,其最大结合 ( Bmax)为 SR的 1 / 68,而离解常数 ( Kd)为 SR的 61 %。与假手术组相比 ,术后 4周大鼠心肌显著肥厚 ,左室重量指数增加 4 4 % ,左心功能代偿性增加 ,心肌 SR的 Ry R最大结合增加2 0 % ,而 NE的该受体 Bmax则增加 1倍 ,SR与 NE的 Bmax比值显著降低 ( P<0 .0 1 ) ;Kd与对照组接近。结论 :大鼠心肌细胞 NE上存在低密度、高亲和 Ry R,心肌肥厚时心肌 SR和 NE的 Ry R均上调 ,而 NE的受体增加幅度更大 ,这些改变可能参与心肌肥厚时心功能代偿和核反应异常的发生。
OBJECTIVE: To investigate the changes of ryanodine receptor (RyR) in cardiac sarcoplasmic reticulum (SR) and nuclear envelope (NE) of myocardial hypertrophy in rats and further investigate the mechanism of cardiac hypertrophy. Methods: The model of cardiac hypertrophy was made by abdominal aorta constriction. Myocardial SR and NE were isolated by differential centrifugation and density gradient centrifugation, and the kinetic characteristics of RyR were studied using isotope labeled ligands. RESULTS: There was also Ry R in NE of cardiomyocytes, the maximum binding (Bmax) was 1/68 of SR, and the dissociation constant (Kd) was 61% of SR. Compared with the sham-operation group, the myocardial hypertrophy was observed at 4 weeks after operation in rats. The left ventricular mass index increased by 44%, compensatory increase of left ventricular function, and maximal RyR of myocardial SR increased by 20% Bmax increased by 1 time, the Bmax ratio of SR and NE decreased significantly (P <0.01); Kd was close to that of control group. CONCLUSION: Myocardial cell NE is characterized by low density and high affinity Ry R in myocardium. RyR of myocardium SR and NE are upregulated in cardiac hypertrophy, and receptors of NE are increased more significantly. These changes may be involved in cardiac function during cardiac hypertrophy Compensation and the occurrence of abnormal nuclear reaction.