脂多糖对血管平滑肌细胞表达MMP-2、9及TIMP-1、2的影响

目的 探讨脂多糖(1ipopolysaccharides，LPS)对培养的大鼠血管平滑肌细胞(vascular smooth muscle cell，VSMC)表达基质金属蛋白酶2、9(matrix metalloproteinase-2，-9；MMP-2，MMP-9)及其组织抑制因子1、2(tissue inhibitor of matrix metalloproteinases-1，-2；TIMP-1，TIMP-2)的影响。方法 贴块法进行血管平滑肌细胞培养，细胞免疫化学检测基质金属蛋白酶及其抑制剂的蛋白表达，原位分子杂交分析MMP-9 mRNA表达。结果 LPS是MMP-9的强诱导物。可在蛋白及mRNA水平诱导MMP-9的表达，同时LPS可诱导TIMP-1的表达，作用较对MMP-9减弱。LPS对二者诱导作用强度与LPS的浓度及作用时间呈正相关。LPS降低TIMP-2的表达，其表达与LPS的浓度及作用时间呈负相关。LPS对MMP-2的表达没有明显作用。结论 LPS诱导平滑肌细胞MMP-9、TIMP-1表达的同时可降低TIMP-2的表达，其作用呈浓度时间依赖性，在动脉粥样硬化发病过程中可能起一定作用。

Effects of Lipopolysaccharides on Expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in the Cultured Rat Vascular Smooth Muscle Cells

Objective To study the effects of lipopolysaccharides (LPS) on the expression of the MMP-2, MMP-9, TIMP-1 and TIMP-2 in the cultured rat vascular smooth muscle cells (VSMCs). Methods Rat VSMCs were cultured by a substrate-attached explanted method. The protein expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 was detected by immunohistochemistry and the expression of MMP-9 mRNA by hybridization in situ.Results Immunohistochemistry and hybridization in situ revealed that the protein and mRNA expression of MMP-9 was significantly increased. The change of TIMP-1 expression was the same as that of MMP-9. In contrast, LPS could decrease TIMP-2 protein production, but had no significant effect on the expression of MMP-2. Conclusion LPS induced the expression of MMP-9 and TIMP-1 in a dose- and time-dependent manner. LPS decreased the expression of TIMP-2. We concluded that LPS might play a role in atherosclerosis.