尾加压素对常氧及低氧大鼠肺动脉平滑肌细胞周期的影响

IMPACT OF HUMAN UROTENSIN Ⅱ ON THE PULMONARY ARTERIAL SMOOTH MUSCLE CELLS CYCLE IN NORMOXIC/HYPOXIC RATS

目的 :观察新近发现的缩血管活性肽人类尾加压素Ⅱ(humanurotensinⅡ ,hUII)对体外培养的大鼠肺动脉平滑肌细胞 (PASMCs)周期的影响。方法 :体外培养大鼠肺动脉平滑肌细胞 ,加入不同浓度 (mol/L)的hUII(1 0 - 7、1 0 - 8、1 0 - 9) ,在常氧及低氧条件下孵育 1 2h,用流式细胞术碘化丙啶染色法 ,分析PASMCsDNA直方图细胞周期时项、细胞增殖指数及凋亡亚二倍体峰的改变 ,以初步观察hUII对PASMCs增殖与凋亡的影响。结果 :hUII呈浓度依赖方式促进PASMCs的增殖 ,主要表现为细胞周期S期的百分比增加 ,细胞增殖指数 (PI)增高 ,常氧作用比低氧作用更明显。hUII浓度 (mol/L)为 1 0 - 7、1 0 - 8、1 0 - 9时 ,与PASMCs常氧作用 1 2h,PI分别比对照组增加了的 1 75 %、1 35 %、1 1 8% ;低氧作用 1 2h ,PASMCsPI分别是对照组的 1 35 %、1 1 8%、1 0 3 % ,hUII浓度为 1 0 - 7mol/L时作用最明显。同时DNA直方图分析各浓度范围的hUII均未见PASMCs凋亡亚二倍体峰出现。结论 :hUII以剂量依赖方式刺激常氧及低氧PASMCsS期DNA合成速率 ,使PI增高 。

Aim:To investigate the impact of human urotensin II (hUII) on pulmonary arterial smooth muscle cell (PASMCs) cycle in vitro . Methods: PASMCs dissected from wistar rats were cultured in vitro , and incubated with series of concentrations of hUII (10 -7 mol/L,10 -8 mol/L, 10 -9 mol/L)for 12 hours under normoxia or hypoxia condition, in order to analyze cell cycle progression and sub G 1 of PASMCs by using flow cytometric analysis stain of propidium iodide, which represented the proliferative and apoptotic changes in PASMCs.Results:The study showed a does dependent effect of hUII on PASMCs proliferation , which reflected the increase both in percentage of S phase of cell cycle and proliferative index (PI). The response of PASMCs to hUII was different under normoxic and hypoxic conditions. Compared with the control group, the treatemet of 10 -7 mol/L, 10 -8 mol/L and 10 -9 mol/L hUII produced an increase of 175%, 136% and118% under normoxia, respectively, and 135%, 118% and 103% under hypoxia, respectively. The concentration 10 -7 mol/L hUII played a significant role in PASMCs proliferation both under hypoxia and normoxia( P <0.01). The results of cell cycle did not show sub G 1 of PASMCs at various concentrations of hUII.Conclusion:hUII may stimulate DNA synthesis in S phase cell cycle of PASMCs and the proliferation of PASMCs under normoxia and hypoxia conditions,which promote cell growth in a does dependent manner.