κ受体激动对去甲肾上腺素诱导的心肌肥大的抑制作用

目的　利用体外培养的乳鼠心肌细胞 ,观测κ阿片肽受体激动对去甲肾上腺素 (norepinephrine ,NE)诱导的心肌肥大的抑制作用 ,并探讨作用机制。方法　对培养乳鼠心肌细胞分组给药 48h后 ,用Lowrys法测心肌细胞的蛋白质含量 ;用消化分离法 ,通过目镜标尺测心肌细胞体积 ;用镜下计数法测心肌细胞的搏动频率。结果　κ阿片肽受体激动剂U5 0 ,488H(简称U5 0 ) (0 1～ 10 μmol·L-1)对培养心肌细胞的蛋白质含量具有抑制作用并呈剂量依赖性 ;对NE诱导的心肌细胞蛋白含量增加、体积增大具有抑制作用 ;同时观察到U5 0 ,488H(1μmol·L-1)具有抑制心肌细胞搏动频率的作用。U5 0 ,488H的上述作用均可被κ阿片肽受体拮抗剂Nor BNI(1μmol·L-1)拮抗。结论　U5 0 ,488H对NE诱导的心肌肥大具有抑制作用 ,这种作用是通过激动κ阿片肽受体发挥的。

Inhibitory effects of κ-opioid receptor stimulation on NE-induced cardiac hypertrophy of the cultured myocardial cells

AIM To study the effects of κ-opioid receptor activation on the cardiac hypertrophy, cultured cardiomyocytes were to used study the inhibitory effects of U58,488H on cellular volume and norepinephrine(NE)-induced hypertrophy in the presence or absence of norbinaltorphimine(nor-BNI). METHODS The protein content was assayed with Lowry's method. The cardiomyocytes'volumes was measured by an eyepiece graticule of inverted microscope. The contracting frequency of cultured myocytes was counted by the inverted microscope. RESULTS A κ-opioid receptor agonist U50,488H at (0.1～10 μmol·L -1 ) inhibited the protein content of cultured myocardial cells in normal serum medium in a dose-dependent manner. The inhibitory effects of U50,488H were completely blocked by pretreatment with nor-BNI, a specific κ-opioid receptor antagonist at 1 μmol·L -1 . U50,488H (0.1～10 μmol·L -1 ) also inhibited NE-induced cellular hypertrophy in low serum medium, which also were abolished by nor-BNI(1 μmol·L -1 ). CONCLUSIONS U50,488H inhibited NE-induced hypertrophy. The inhibitory effects of U50,488H are involved in mediating the action of NE-induced cardiac hypertrophy.