CaMKⅡ信号通路在神经肽Y诱导心肌细胞肥大中的作用

目的：探讨钙离子／钙调蛋白（Ca^2＋／CaM）依赖的蛋白激酶Ⅱ（CaMKⅡ）信号通路在神经肽Y（NPY）诱导下心肌细胞肥大的作用。方法：原代培养SD乳鼠心肌细胞，将细胞分为5组，NPY组：培养液中加入终浓度为100nmol／L的NPY：KN-931组、KN-935组和KN-9310组除加入100nmol／L的NPY外，分别加入CaMKⅡ特异性抑制剂KN-93，终浓度为1μmol／L、5μmol／L和10μmol／L；对照组：培养液中不加任何刺激药品。加药24h后采用 ^3H-亮氨酸（Leu）掺入法测定各组心肌细胞蛋白质合成速率，Western blotting测定对照组与NPY组心肌细胞的CaMKⅡδ蛋白表达。结果：经100nmol／L NPY刺激24h后，可明显增加心肌细胞^3H-Leu掺入量（p〈0．05），KN-93（1-10μmol／L）可以抑制NPY刺激的心肌细胞^3H-Leu掺入量的增加，并呈剂量依赖性（P均〈0．05）；100nmol／L NPY明显增加心肌细胞内CaMKⅡδ蛋白的表达（P〈（0．05）。结论：Ca^2＋／CaM依赖的蛋白激酶Ⅱ（CaMKⅡ）信号途径参与NPY诱导的大鼠心肌细胞肥大反应。

The Role of CaMK Ⅱ Signal Pathway in Neuropeptide-Y-induced Cardiomyocyte Hypertrophy

Objective： To explore the role of Calcium/Calmodulin- dependent protein kinase Ⅱ （CaMK Ⅱ） signaling pathway on neuropeptide Y（NPY）-induced cardiac hypertrophy in rats. Methods： The primarily cultured cardiomyocytes of neonatal Sprague-Dawley rats were randomly divided into five groups, including the NPY group treated with 100 nmol/L NPY, KN-931, KN-935 and KN-9310 groups treated with 1 μmol/L, 5μmol/L and 10 μmol/L KN -93 （a specific inhibitor of CaMK U ）, respectively as add-ons to 100 nmol/L NPY and a control group without any treatment. After 24- hour stimulation, ^3H-Leu incorporation was used to assess protein synthesis rate and Western blotting was employed to measure CaMK Ⅱδ protein expression in these cardiomyocytes. Results： ^3H-Leu incorporation of cardiomyocytes increased significantly with 100 nmol/L NPY after 24 hours （P〈0.05）. KN-93 was shown to decrease the NPY-induced ^3H-Leu incorporation in a dose-dependent manner. In addition, the CaMK Ⅱδ protein expression in cardiomyocytes was remarkably elevated by 100 nmol/L NPY （P〈0.05）. Conclusion： CaMK Ⅱ pathway may have a role in neuropeptide Y-induced cardiomyocvtcs hypertrophy.