Ca^(2+)信号在肿瘤坏死因子-α诱导心肌肥大PI3-K信号途径中的作用  

Ca^(2+) is involved in tumor necrosis factor-α induced cardiomyocyte hypertrophy through PI3-kinase pathway in rats

作　　者：王桂君[1] 姚玉胜[2] 李戆鹏[1] 王洪新[3] 

机构地区：[1]辽宁医学院附属第一医院,锦州121000 [2]辽宁医学院附属第二医院,锦州121000 [3]辽宁医学院药理学教研室,锦州121000

出　　处：《中国应用生理学杂志》2010年第3期284-288,共5页Chinese Journal of Applied Physiology

摘　　要：目的:研究Ca2+信号在肿瘤坏死因子-α(TNF-α)诱导心肌细胞肥大PI3-K信号途径中的作用。方法:Lowry法测心肌细胞蛋白含量;计算机图像分析系统测心肌细胞体积;[3H]-亮氨酸掺入法测心肌细胞蛋白合成;Till阳离子测定系统观察胞内[Ca2+]i瞬变。结果:①TNF-α(100μg/L)明显诱导心肌细胞蛋白含量、蛋白合成及体积的增加,PI3-K特异性抑制剂LY294002(50μmol/L)明显抑制TNF-α诱导的心肌肥大,但对正常心肌细胞生长无影响。L型Ca2+通道阻断剂verapamil(1μmol/L)对TNF-α诱导的心肌肥大无明显影响。②TNF-α引起心肌细胞内钙离子浓度([Ca2+]i)瞬间变化幅度增高,LY294002明显降低TNF-α诱导的上述改变,L型Ca2+通道阻断剂verapamil(1μmol/L)对TNF-α引起的变化无明显影响。结论:PI3-K可能通过引起心肌细胞[Ca2+]i升高参与TNF-α诱导的心肌细胞肥大,但与L型Ca2+通道无关。Objective： To investigate whether Ca^2 ＋ contribute to cardiomyocyte hypertrophy induced by tumor necrosis factor-α （TNF-α） through PI3-kinase pathway. Methods： The protein content was assayed with Lowry＇ s method . The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-lencine incorporation method. [ Ca^2＋]i transient was measured by Till image system by cell-loading Fura-2/AM. Results： （1）TNF-α significantly induced the increase of protein content, [^3H]-leucine incorporation and cell size. These responses were significantly suppressed by LY294002, a selective PI3-kinase inhibitor. Verapamil, L-type calcium channels antagonist, slightly attenuated TNF-α-induced these responses. （2）TNF-α increased the amplitude of the spontaneous Ca^2＋ transients in cultured ventricular myocytes from the neonatal rat; PI3-kinase inhibitor LY294002 could suppress the elevation induced by TNF-a, but calcium antagonist verapamil took the minor effects of TNF-α on [ Ca^2＋ ]i metabolism. Conclusion： Increasing the intercellular free Ca^2 ＋ level may play an essential role in TNF-α-induced cardiomyocyte hypertrophy through PI3-kinase pathway in rats, while L-type calcium channel takes the minor effects on it.

关 键 词：心肌肥厚 肿瘤坏死因子-Α 钙离子 磷脂酰肌醇-3激酶 L型Ca^2+通道 

分 类 号：R972[医药卫生—药品]