神经肽Y经Ca^2＋/CaM依赖的钙调神经磷酸酶途径诱导心肌细胞肥大  

Role of Ca^(2+)/calmodulin-dependent calcineurin signaling pathway in neuropeptide Y-induced cardiac hypertrophy in rats

作　　者：李晓云[1] 陈敏生[1] 黄少华[2] 董颀[3] 李荧辉[4] 张舒[5] 刘振秀[4] 

机构地区：[1]广州医学院第二附属医院心内科,广东广州510260 [2]广州医学院第一附属医院,广东广州510120 [3]广州医学院生理教研室,广东广州510120 [4]航天医学工程研究所,北京100094 [5]第四军医大学生理系,陕西西安710033

出　　处：《南方医科大学学报》2008年第12期2139-2141,共3页Journal of Southern Medical University

基　　金：国家自然科学基金(30440053);广东省自然科学基金(4004529)

摘　　要：目的观察神经肽Y(NPY)诱导心肌细胞肥大效应,及Ca2+/CaM依赖的钙调神经磷酸酶(CaN)途径在其中起的作用。方法用NPY(10、100nmol)刺激心肌细胞,用环胞素A(CsA)特异性抑制CaN活性。测定心肌细胞蛋白合成速率(3H-Leu掺入量)、CaN-蛋白表达、c-junmRNA表达、CaN酶活性、细胞内游离钙含量。结果(1)在100nmolNPY作用下,心肌细胞3H-Leu掺入量及c-junmRNA表达量均较对照组显著增高(P<0.05,P<0.001)。NPY+CsA组和对照组相比无显著差别。(2)在100nmolNPY作用下,NPY组心肌细胞内CaN酶比活力、CaN-α表达、胞浆及核内钙含量较对照组显著增高(P<0.05,P<0.05,P<0.001,P<0.001)。结论NPY可刺激心肌细胞肥大,CaN信号途径在其中起重要作用。Objective To investigate the role of Ca^2＋/calmodulin-dependent calcineurin （CAN） signaling pathway in neuropeptide Y （NPY）-induced cardiomyocyte hypertrophy in rat. Methods Cardiomyocytes of neonatal Wistar rats were cultured in the presence of 10 and 100 nmol/L NPY, and cyclosporine A （CsA） was applied to inhibit the activity of CaN. The protein synthesis rate, c-jun mRNA expression, CaN protein expression, CaN activity and intracellular Ca^2＋ concentration in the cardiomyocytes were assessed. Results Compared with the control group, 3H-Leu incorporation and expression of c-jun mRNA in the cardiomyocytes treated with 100 nmol/L NPY increased significantly （P〈0.05, P〈0.001）, and the effect of NPY was blocked by CsA. The activity of CaN （P〈0.05）, CaN expression （P〈0.05）, and Ca^2＋ concentration in the cytoplasm （P〈0. 001） and nuclei （P〈0.001） of the cells with 100 nmol/L NPY treatment also significantly increased compared with those in the control cells. Conclusion NPY can induce cardiomyocyte hypertrophy in rats, in which process Ca^2＋/calmodulin-dependent CaN signaling pathway plays an important role.

关 键 词：神经肽Y 钙调神经磷酸酶 胞内钙 心肌细胞肥大 

分 类 号：R544.1[医药卫生—心血管疾病] R541.3[医药卫生—内科学]