1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐对肥厚心肌DNA含量和培养心肌细胞DNA合成的影响

为研究1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基) 丙烷盐酸盐(DDPH)对心肌肥厚大鼠左室组织 DNA 含量有无逆转作用, 用部分狭窄腹主动脉的方法建 立心肌肥厚的模型. 术后wk4开始给药, 连续8 wk, 左室心肌切片并进行 Feulgen染色, 用 TJTY-300 图像分析系统对DNA进行相对定量, 发现肥厚组平均吸光度为0.089, 是对照组的1.43倍,而二个给药组分别为0.079和0.071, 明显低于肥厚组, 但仍高于对照组(P<0.05), 说明DDPH对肥厚心肌的 DNA 含量有一定的逆转作用. 为进一步研 究 DDPH 能否抑制去甲肾上腺素 (NE) 致培养乳鼠心肌细胞DNA合成的作用, 体外培养乳鼠心肌细胞, 实验分 6 组: (1) 对照组; (2) NE组; (3) DDPH 1.0 μmol·L^-1组; (4) DDPH 10 μmol·L^-1组; (5) 哌唑嗪(Pra) 1.0 μmol·L^-1组; 6) Pra 10 μmol·L^-1组. 每孔加［³H］TdR 37 Bq, 3 h后测 cpm 值, 发现 NE 组为对照组的3.1倍,而 DDPH 及 Pra 组均减少 cpm 值 (P<0.01), 且 Pra 组作用更明显, 二个高剂量组与对照组无显著差异, 结果说明 DDPH 可以抑制 NE 诱导的乳鼠心肌细胞 DNA 合成的增加.

Effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethyl-amino)- propane hydrochloride on DNA content in hypertrophic myocardium and DNA synthesis in cultured myocardial cells

To investigate the reversing effect of DDPH on DNA content in left ventricle tissue of rats with cardiac hypertrophy, the model of cardiac hypertrophy was made by partly narrowing abdominal aorta. At wk 4 after operation, the rats were given drugs for 8 wk. DNA was specially stained by Feulgen method, and the relative content was determined by TJTY-300 image processing system. It was found that the average light density in model group was 0.089, that was 1.43 times of that in control group, DDPH 25 and DDPH 50 mg·kg^-１·d^-１ groups were 0.079 and 0.071, significantly lower than that in model group (P<0.05 and P<0.01, respectively), but still higher than that in control group (P<0.05). It indicated that DDPH has certain effect on reversing DNA content in left ventricle tissue of rats with cardiachypertrophy. To further investigate the inhibitory effect of DDPH on DNA synthesis in cultured myocardium stimulated by norepinephrine(NE), myocardium of newborn rats was cultured in cultivating plate with 24 holes, the cells were divided into 6 groups, each having 4 holes: 1) control; 2) NE; 3) DDPH 1.0 μmol·L^-1; 4) DDPH 10 μmol·L^-1; 5) Pra 1.0 μmol·L^-1; 6) Pra 10 μmol·L^-1. In each hole was added 37 Bq ［³H］TdR, radioactivity was determined 3 h later, it was found that the value in model group was 3.1 times of that in control groups. Both DDPH and Pra groups could significantly decrease the value (P<0.01), and the effect of higher dosage was more obvious, Pra was more efficient than DDPH at the same dosage. It is concluded that DDPH can inhibit DNA synthesis in myocardium stimulated by NE.