丹参对血管平滑肌细胞基质金属蛋白酶和骨桥蛋白基因表达及细胞增殖的影响

Effects of Salvia miltiorrhiza on Matrix Metalloproteinases and Osteopontin Gene Expression and Proliferation of Cultured Vascular Smooth Muscle Cells

目的 :探讨丹参 (SAL)对氧化低密度脂蛋白 (ox LDL)诱导体外培养的血管平滑肌细胞(VSMC)基质金属蛋白酶 (MMP)和骨桥蛋白 (OPN)基因表达的影响 ,以提示SAL抑制VSMC增殖和迁移的作用机理。方法 :应用Northern、Western印迹和斑点杂交检测SAL对MMP 2、MMP 9和OPN表达的影响 ;采用3H TdR掺入实验 ,检测VSMC增殖活性。结果 :SAL或复方丹参 (SALC)注射液对ox LDL诱导的MMP 2和MMP 9表达以及OPN的合成与分泌具有明显的下调作用 ,且可显著抑制VSMC的DNA合成 ;将ox LDL与SAL或SALC注射液共孵育 1h后再处理VSMC ,ox LDL对上述基因表达和VSMC增殖的诱导作用基本消失。结论 :SAL抗VSMC增殖与迁移的作用与其调整基质代谢有关。

Objective: To study the effect of Salvia on gene expression of matrix metalloproteinase 2 (MMP 2), MMP 9 and osteopontin (OPN) induced by oxidized low density lipoprotein (ox LDL) in cultured rat vascular smooth muscle cell (VSMC). Methods: Northern blot, dot blot and western blot were used to analyse the changes of MMP 2, MMP 9 and OPN expression, 3?H TdR incorporation was used to detect the DNA synthesis to estimate the proliferative activity of VSMC. Results: The ox LDL induced MMP 2, MMP 9 expression as well as synthesis and secretion of OPN could down regulated obviously by Salvia or composite Salvia injection (SALC), they could also inhibit the DNA synthesis of VSMC. When VSMC was treated by ox LDL co incubated with Salvia or SALC for 1 hr, the induction of MMP expressions and cell proliferation decreased significantly. Conclusion: Salvia plays an important role in regulating extracellular matrix metabolism, which might be the mechanism in depressing VSMC proliferation and migration.