去甲肾上腺素促进兔肺动脉平滑肌细胞增殖的受体亚型研究

Study of subtypical adrenoceptors in the proliferation of rabbit PASMCs induced by NE

目的：观察肾上腺素能受体亚型β１、α１、α２在去甲肾上腺素（ＮＥ）促进肺动脉平滑肌细胞（ＰＡＳＭＣ）增殖中的作用，并观察钙通道阻滞剂的影响．方法：离体培养新西兰兔ＰＡＳＭＣ，采用四唑盐比色法（ＭＴＴ）和３Ｈ－ＴｄＲ参入实验观察ＰＡＳＭＣ增殖和ＤＮＡ合成量的变化．结果：ＮＥ（１×１０－５～１×１０－４ｍｏｌ／Ｌ）对ＰＡＳＭＣ的增殖和ＤＮＡ的合成有显著的促进作用．β１受体阻断剂Ｐｒｏｐｒａｎｏｌｏｌ使四唑盐比色法（ＭＴＴ）的吸光度（Ａ）和３Ｈ－ＴｄＲ参入率分别下降２５％和２１．８％；α１受体阻断剂ｐｒａｚｏｓｉｎ（１×１０－４ｍｏｌ／Ｌ）使ＭＴＴ的Ａ值和３Ｈ－ＴｄＲ参入率分别下降２９．５％和３５．７％；而α２受体阻断剂ｙｏｈｉｍｂｉｎ（１×１０－３ｍｏｌ／Ｌ）无显著影响．钙通道阻滞剂ｖｅｒａｐａｍｉｌ和ｎｉｆｅｄｉｐｉｎｅ（１×１０－６ｍｏｌ／Ｌ）使ＭＴＴ的Ａ下降３１％和３６％，使３Ｈ－ＴｄＲ参入率下降３６％和４０％．结论：ＮＥ能促进ＰＡＳＭＣ的增殖和ＤＮＡ合成，此效应主要是通过β１和α１受体介导的，可能和α２受体无明显关系．细胞内的Ｃａ２＋增加是ＮＥ促进ＰＡＳＭＣ增殖的重要原因．

Objective: To investigate the actions of β 1 and α 1, α 2 subtypical adrenoceptors in the proliferation of the pulmonary arterial smooth muscle cells (PASMCs)induced by noradrenalin (NE)and observe the effects of calcium channel antagonists. Methods: Rabbit PASMC culture in vitro , MTT method and 3H TdR incoporation were used. Results: 1×10 -5 ～1×10 -4 mol/L NE markedly stimulated the proliferation and the DNA synthesis of PASMC. Propranolol (1×10 -5 mol/L), β 1 ardenoceptor antagonist, decreased the absorbance ( A ) of MTT and 3H TdR incorporation by 25%, 21.8% and Prazosin, α 1 ardenoceptor antagonist by 29.5%, 35.7% respectively. No effects of yohimbin(1×10 -3 mol/L), α 2 ardenoceptor antagonist, on the A value of MTT and 3H TdR incorporation were observed. Calcium channel antagonist verapamil(1×10 -3 mol/L)decreased the A value of MTT and 3H TdR incorporation by 31%, 36%, and nifedipine by 36%, 40% respectively. Conclusion: NE can stimulate the proliferation and DNA synthesis of PASMC, which is mainly mediated through β 1 and α 1 adrenoceptors, while having no relation to α 2 adrenoceptor. The proliferation of PASMC induced by NE is significantly due to the increasing of cytoplasmic calcium.