霉酚酸对内皮素-1诱导的肺动脉平滑肌细胞增殖迁移收缩的影响

目的 研究霉酚酸对内皮素-1诱导的大鼠肺动脉平滑肌细胞(PASMCs)的增殖、收缩和迁移的影响,探讨霉酚酸酯对肺动脉高压的作用机制.方法 采用四甲基偶氮唑蓝(MTT)、划痕实验、Millicell培养小室及测微尺计量的方法观察霉酚酸对内皮素-1诱导PASMCs增殖、迁移和收缩的影响,并了解鸟嘌呤对霉酚酸抑制PASMCs增殖的逆转作用.采用配对t检验进行统计分析.结果 与内皮素-1组相比,低浓度霉酚酸组平滑肌细胞增殖降低吸光度(A)值:0.348±0.036与0.447±0.013,t=6.357,P=0.000];高浓度MPA组进一步降低.与低浓度霉酚酸组相比,霉酚酸加鸟嘌呤组平滑肌细胞增殖有所增加(A值:0.390±0.018与0.348±0.036,t=2.573,P=0.028).霉酚酸组细胞平均迁移距离较内皮素-1组缩短,霉酚酸组平均迁移细胞数较内皮素-1组减少,霉酚酸组平均细胞长度长于内皮素-1组.结论 霉酚酸具有抑制内皮素-1诱导的PASMCs增殖、迁移和收缩的作用,外源性鸟嘌呤可部分逆转霉酚酸抑制PASMCs增殖的作用.

The effects of mycophenolic acid on the endotheline-1 induced proliferation, contraction and migration of pulmonary arterial smooth muscle cells: in vitro study

Objective To investigate the effect of mycophenolic acid (MPA) on the endotheline-1 (ET-1) induced proliferation, contraction and migration of pulmonary arterial smooth muscle cells (PASMCs)and to explore the mechanism of MPA on pulmonary arterial hypertension (PAH), and the effect of exogenous guanosine nucleotide reversing anti-proliferative effect of MPA. Paired-samples t-test was used for statistical analysis. Methods MTT test, scarification test, Millicell cell culture insertion and the length of PASMCs mcasured under microscope were used. Results The A values of group ET-1 + low concentration MPA decreased when compared with group ET-1 (0.348±0.036 vs 0.447±0.013, t=6.357, P=0.000) and the A values of group ET-1 + high concentration MPA was further decreased. The A values of group ET-1 + low concentration MPA + guanosine was higher than that of group ET-1 + low concentration MPA (0.390±0.018 vs 0.348 ±0.036, t=2.573, P=0.028). The average migration distance and the average migration numbers of PASMCs of groups MPA was decreased than that of group ET-1. The average cell length of PASMCs of groups MPA was increas ed than that of group ET-1. Conclusion MPA can effectively inhibit the proliferation,contraction and migration of PASMCs by ET-1 induction. The IMPDH may play a role in anti-proliferative effect of MPA on PASMCs, but is unnecessary to be the sole mechanism. These findings has provide new insight into the mechanisms of mycophenolate mofetil in the treatment of PAH.