硫化氢对培养的大鼠主动脉平滑肌细胞增殖的抑制作用

Inhibitory effect of hydrogen sulfide (H_2S) on cultured rat aortic smooth muscle cells

目的 :探讨硫化氢 (H2 S)对内皮素 - 1(ET - 1)诱导的血管平滑肌细胞 (VSMC)增殖的影响及丝裂原激活的蛋白激酶 (MAPK)信号转导途径的作用。方法 :体外培养雄性SD大鼠主动脉VSMC ,将细胞分成对照组、血清组、内皮素组、NaHS组、血清 +NaHS组和内皮素 +NaHS组进行研究 ,以不同浓度梯度NaHS处理VSMC ,观察对VSMC [3 H]-TdR掺入和MAPK活性的影响。结果 :加入 5× 10 -5- 5× 10 -4mol/LNaHS可明显浓度依赖性地抑制由内皮素诱导的VSMC增殖 ,其 [3 H]-TdR掺入量减低 ,抑制率分别为 16 .8% - 37.4 % (P <0 .0 1) ,其MAPK活性明显减低 ,抑制率为 7.4 % - 33.6 % (P <0 .0 5或P <0 .0 1)。结论 :H2 S对内皮素诱导的VSMC增殖有抑制作用 ,同时使MAPK活性下调。推测H2 S对VSMC增殖的抑制效应可能由MAPK信号途径所介导。

AIM: To explore the effects of hydrogen sulfide (H_2S) on proliferation of vascular smooth muscle cells (VSMC) stimulated by endothelin (ET-1, 10 -7 mol/L ) and mitrogen-activated protein kinase (MAPK) activity in VSMCs. METHODS: Cultured VSMCs were divided into six groups: (1) control group, (2) serum group, (3) endothelin group, (4) NaHS groups, (5) serum+NaHS group, and (6) endothelin+NaHS group. VSMC proliferation was measured by [ 3H]-TdR incorporation and MAPK activity in VSMC was determined by radioactivity assay. RESULTS: ET-1 increased VSMC [ 3H]-TdR incorporation by 2.39 times ( P< 0.01) and MAPK activity by 1.62 times( P< 0.01), as compared with control. H_2S (5×10 -5 -5×10 -4 mol/L) decreased VSMC [ 3H]-TdR incorporation and MAPK activity by 16.8%-37.4% and 7.4%-33.6%, respectively ( P <0.05 or P< 0.01). CONCLUSION: This study demonstrates that H_2S inhibits ET-1-induced proliferation of VSMC,which might be mediated by the inhibition of MAPK.