多巴胺系统及L-精氨酸／一氧化氮通路在大鼠心肌肥大中的作用研究

Effects of L-Arginine/nitric oxide pathway on myocardial hypertrophy

目的 探讨多巴胺系统及L-精氨酸／一氧化氮（L—Arg／NO）通路在大鼠心肌肥大动物模型中的作用及相关机制。方法 采用腹主动脉缩窄术复制大鼠心肌肥大动物模型。将Wistar大鼠随机分为4组：①腹主动脉缩窄术（AC）组；②假手术（SO）组；③L-精氨酸（L—Arg）组；④左旋硝基精氨酸甲酯（L—NAME）组。通过心肌肥大指数，心肌组织胶原染色，心功能检测等方法分析各组大鼠心肌组织肥大状况：采用RT—PCR和Western blot结合图像分析系统，观察药物干预后，心肌组织中多巴胺受体D1、D2mRNA和蛋白质表达变化：借助紫外分光光度计，分析心肌组织匀浆中一氧化氮（NO）水平和一氧化氮合酶（NOS）活性。结果 AC组左心肥大明显．表现为室内压显著升高，胶原增多；与SO组比较，腹主动脉缩窄术后D1、D2mRNA和蛋白质表达均明显降低（P〈0.01），NO、NOS水平明显下降（P〈0.01）；应用NOS抑制剂L-NAME预处理能够促进肥大的发生。使用NO合成的前体L-Arg干预，则抑制肥大发生。结论 压力负荷加大能引起心肌肥大。其机制可能与NO合成减少有关：大鼠心肌细胞内存在多巴胺受体D1、D2mRNA和蛋白质表达，心肌肥厚时二者均明显减低。

Objective To explore the role and possible mechanisms of dopamine system and L- Arginine/nitric oxide （L-Arg/NO） pathway in myocardial hypertrophy. Methods Hypertrophy model of rats was established using abdominal aorta coarctation. Wistar rats were randomly divided into four groups： abdominal aorta coaretation（AC） group, sham-operation（SO） group, L-Arg group, L-NAME group. Hypertrophy status of rats were determined by hypertrophy coefficient, collagen content and heart function; RT-PCR and Western blot integrating image analysis system were applied to examine D1, D2 mRNA and protein expression in rat heart, respectively; Spectrophometer were employed to measure NO content and NOS activity. Results A Significant hypertrophy of left ventricle occurred in the rats of AC group, which was characterized by the raising of ventricle pressure and collagen content; Both dopamine receptor D1, D2 mRNA and protein were detected in normal rat heart; Compared with SO group, D1, D2 mRNA and protein were remarkably decreased in AC group （P 〈 0.01 ）, while NO content and NOS activity have obviously decreased （P 〈 0.01 ） ; Hypertrophy coefficient increased in L-NAME group and reduced in L- Arg group. Conclusions Myocardial hypertrophy can be induced by abdominal aorta coarctation, whose mechanism is related with decreased NO in cardiomyocytes; Both D1 and D2 exist in normal rat heart and remarkably decreases in myocardial hypertrophy.