内源性一氧化碳对内皮素-1诱导的大鼠血管平滑肌细胞增殖的抑制作用

The inhibition of endogenous carbon monoxide on vascular smooth muscle cell proliferation induced by endothelin 1

目的探讨内源性一氧化碳（ＣＯ）对内皮素１（ＥＴ１）诱导的血管平滑肌细胞（ＶＳＭＣ）增殖的影响。方法体外培养Ｗｉｓｔａｒ鼠主动脉ＶＳＭＣ，用ＥＴ１诱导其增殖，用氯血红素诱导血红素氧合酶１（ＨＯ１），促进ＣＯ生成，测定培养上清液中碳氧血红蛋白（ＣＯＨｂ）含量和ＶＳＭＣｓ３Ｈ胸腺嘧啶核苷（３ＨＴｄＲ）参入量。结果加入梯度浓度氯血红素１０μｍｏｌ／Ｌ、２０μｍｏｌ／Ｌ、４０μｍｏｌ／Ｌ，培养上清液中ＣＯＨｂ量分别增高８．３％、１４．６％和１６．７％（Ｐ＜０．０５或Ｐ＜０．０１），对由ＥＴ１增高的ＶＳＭＣｓ３ＨＴｄＲ参入量抑制率分别为２２．９％，４３．９％和５１．７％（Ｐ＜０．０１），与加入的氯血红素及上清液中ＣＯＨｂ含量呈浓度依赖关系。结论ＶＳＭＣｓ产生的ＣＯ对ＥＴ１刺激的平滑肌细胞的增殖有抑制作用。提示血红素ＨＯＣＯ系统在血管重塑中有一定作用。

Objective To determine the effect of endogenous carbon monoxide (CO) on vascular smooth muscle cells (VSMCs) proliferation induced by endothelin 1 (ET 1).Methods Wistar rat aortic VSMCs were cultured in vitro and stimulated to proliferate by endothelin 1 (ET 1 10 -7 mol/L), hemin (a substrate and inducer of HO 1) was added in gradient concentrations of 10, 20 and 40μmol/L to induce CO production. The relative amount of CO released into the media was quantitated as carbon monoxide hemoglobin (COHb). Results With hemin added in gradient concentrations, 3H TdR incorporations of VSMCs were reduced 22.9%, 43.9% and 51.7%, respectively ( P <0.01). The reduction was dependent on the amount of added hemin and the concentration of COHb in the media. Conclusion Endogenous CO released from VSMCs has an inhibitive effect on VSMCs proliferation induced by endothelin 1 (ET 1). The HO CO system might play an important pathophysiologic role in the vasculature remodeling when high level of ET 1 is present.