CaMKⅡ信号通路在神经肽Y诱导心肌细胞肥大中的作用  

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

作　　者：林晓圳[1] 董颀[2] 石永英[1] 张弋[3] 陈敏生[1] 

机构地区：[1]广州医学院第二附属医院心脏内科,广东广州510260 [2]广州医学院生理教研室,广东广州510182 [3]广州医学院第二附属医院急诊科,广东广州510260

出　　处：《广州医学院学报》2008年第1期10-13,共4页Academic Journal of Guangzhou Medical College

基　　金：国家自然科学基金资助项目(30440053;30570759);广东省自然科学基金资助项目(04004529)

摘　　要：目的:探讨钙离子/钙调蛋白(Ca2+/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,Westernblotting测定对照组与NPY组心肌细胞的CaMKⅡδ蛋白表达。结果:经100nmol/LNPY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/LNPY明显增加心肌细胞内CaMKⅡδ蛋白的表达(P<0.05)。结论:Ca2+/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。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.

关 键 词：钙调蛋白激酶Ⅱ 神经肽Y 心肌细胞 动物实验 大鼠 

分 类 号：R542.2[医药卫生—心血管疾病]