非对称二甲基精氨酸诱导大鼠心肌细胞肥大的作用

目的：探讨非对称二甲基精氨酸（ADMA）诱导心肌细胞肥大的作用机制。方法：原代取材新生SD大鼠的心肌细胞进行细胞培养。原代培养的第4天，用不同浓度的ADMA（4～16μmol／L）和L-精氨酸（L-arg）（0．8～3．2mmol/L）处理心肌细胞，24h后测定细胞上清液中一氧化氮（NO）的含量、一氧化氮合酶（NOS）的活性，细胞内氧活性物质（ROS）的水平、RNA含量、总蛋白量以及心肌细胞表面积。结果：①4μmol／L，8μmol／L，16μmol／L的ADMA分别能剂量依赖性使细胞内NO的含量减少，NOS的活性降低（P〈0．05）；②16μmol／L的ADMA能使心肌细胞内ROS的水平升高、细胞内RNA含量和总蛋白含量增加以及心肌细胞表面积增加（P〈0．05）；⑧0．8mmol／L，1．6mmol／L，3．2mmol/L的L-arg对ADMA诱导的心肌细胞内ROS水平的升高、细胞内RNA含量和总蛋白含量的增加以及心肌细胞表面积的增加产生剂量依赖性的抑制作用（P〈0．05）。结论：ADMA能够诱导心肌细胞肥大，NO的前体L-arg能够剂量依赖性地抑制ADMA诱导的心肌细胞肥大。

Induced Cardiomyocyte Hypertrophy in Rats by Asymmetric Dimethyl-arginine

Objective： To study the mechanism by which asymmetric dimethyl-arginine （ADMA） induced cardiomyocyte hypertrophy in rats. Methods： On day 4 of primary culture, neonatal rat cardiomyocytes were incubated with varied combination and levels of ADMA （4-16μmol/L） and L-arg （0.8-3.2 mmol/L） for 24 hours. The levels of nitric oxide （NO） and activity of nitric oxide synthase （NOS） in the conditioned medium, levels of ROS, total intracellular RNA and proteins, total cellular surface area were determined. Results： ①Incubation with 4, 8 and 16 μmol/L ADMA decreased contents of NO and NOS activities in cardiomyocytes in a dose-dependent manner （P〈0.05）.② Incubation with 16 μmol/L ADMA led to an rise in the levels of ROS, total RNA and proteins in cardiomyocytes （P〈0.05）.③ L-arginine （0.8, 1.6 and 3.2 mmol/L） showed dose-dependently inhibition on the ADMA-induced increase of ROS levels, total RNA and proteins, and total celluar surface area （P〈0.05）. Conclusions： ADMA may induce hypertrophy in neonatal rat cardiomyocytes, while the NO precursor, L-arginine, appears to inhibit ADMA-induced hypertrophy in dose-dependent manner.