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为了研究细胞核三磷酸肌醇受体在心肌肥厚中的作用 ,制备了腹主动脉缩窄大鼠心肌肥厚模型、用差速离心和密度梯度离心提纯心肌细胞核 ,以 [3H]IP3为配基 ,采用放射受体分析心肌细胞核膜IP3R与其配体的最大结合容量 (Bmax)和解离常数 (Kd)。大鼠心肌细胞核上存在IP3R、CaM和PKC激动剂PMA ,能显著抑制该受体与IP3的结合 (P <0 0 5 ) ;核外 [Ca2 +]也能剂量依赖的抑制细胞核IP3R与IP3的结合。腹主动脉缩窄术后 4周 ,大鼠心肌显著肥大 ,伴有明显的血流动力学异常 ,其心肌细胞核IP3R的Bmax和Kd与对照组比较分别增加 1 2 17和2 14 9倍 (P <0 0 1)。心肌细胞核上存在IP3R ,并受CaM和PMA及核外 [Ca2 +]所抑制 ,心肌细胞核IP3R密度上调和亲和力降低可能参与了压力超负荷心肌肥厚的发生过程。
In order to investigate the role of nuclear inositol 1,4,5-triphosphate receptor in cardiac hypertrophy, a rat model of cardiac hypertrophy induced by abdominal aorta was prepared. Cardiomyocyte nuclei were purified by differential centrifugation and density gradient centrifugation. [3H] IP3 was used as ligand, The maximum binding capacity (Bmax) and dissociation constant (Kd) of cardiomyocyte nuclear membrane IP3R and its ligand were analyzed by radioactive receptor. The presence of IP3R, CaM and PKC agonist PMA in the nuclei of rat myocardial cells significantly inhibited the binding of this receptor to IP3 (P <0 05); extranuclear [Ca2 +] also dose-dependently inhibited nuclear IP3R and IP3 Combined. At 4 weeks after abdominal aorta constriction, myocardial hypertrophy was observed in rats with significant hemodynamic abnormalities. The Bmax and Kd of IP3R in nucleus pulposus were increased by 1217 and 2 14 9 times (P <0 0 1). The presence of IP3R on the nucleus of myocardial cells is inhibited by CaM and PMA and extracellular [Ca2 +], and the increased density and decreased affinity of IP3R in myocardial nuclei may be involved in the development of hypertrophic cardiac hypertrophy.