左旋精氨酸抑制人血管平滑肌细胞合成胶原的作用

目的:探讨内皮素(ET-1)对人血管平滑肌细胞(HVSMC)合成胶原的影响并观察左旋精氨酸(L-arginine)对HVSMC合成胶原的影响。方法:将ET-110-8mol/L和不同浓度L-arginine加入体外培养HVSMC。培养24h之后测培养液中NO含量,测细胞内cGMP含量及3H-脯氨酸掺入量即总胶原含量。结果:加入梯度浓度L-arginine,NO水平呈剂量依赖性增加(P均<0.01);ET-1使胶原合成量增加80%(P<0.001),加入梯度浓度L-arginine较ET-1组胶原合成量分别减少了37%、41%、56%(P均<0.01),呈剂量依赖性;ET-1+L-arginine低、中、高浓度组较ET-1组细胞内cGMP含量明显增加(P均<0.01),且cGMP含量随L-arginine增加而增加;细胞内cGMP含量与胶原合成量呈良好负相关关系(r=-0.93)。结论:ET-1可引起HVSMC合成胶原增多;L-arginine可剂量依赖地抑制HVSMC合成胶原;L-arginine对胶原合成的抑制作用可能是通过cGMP途径起作用。

L-arginine inhibits collagen synthesis in human vascular smooth muscle cells

Objective: To study the effect of ET-1 on collagen synthesis of cultured HVSMC, to observe the effect of L-arginine on ET-1 induced collagen synthesis of HVSMC and to explore the mechanism of preventing RS by L-arginine. Methods: HVSMC were cultured in vitro. The HVSMC were administered ET-1 (10~ -8mol/L) and L-arginine of different conlentration. The medium was collected after 24 hours to determine NO. The cells were harvested at the same time to assay cGMP content. The medium and the cells were harvested separately to determine collagen. Results: The level of NO was significantly increased in ET-1 L-arginine group compared with that in ET-1 group (P<0.01). The collagen level in ET-1 group was increased by 80% compared with that in C group (P<0.001). With L-arginine added in gradient concentrations, the production of collagen was decreased in a concentration-dependent fashion: 37%, 41% and 56%, respectively (P all<0.01). The level of cGMP in ET-1 L-arginine group was significantly higher than that in ET-1 group (P all<0.01). Linear correlation: There was a significant negative correlation between the level of cGMP and that of collagen (r=-0.93, P<0.01). Conclusion: ET-1 increased the synthesis of collagen in HVSMC, which was an important cause of intimal hyperplasia in RS. L-arginine inhibited synthesis of collagen of HVSMC in a concentration-dependent fashion, thus it could inhibit intimal hyperplasia. L-arginine inhibited production of collagen, during which the signaling molecule cGMP played an important role in mediating the intracellular signal transduction.