活性氧对平滑肌细胞合成基质金属蛋白酶-1,3及其抑制物的影响

Regulation by reactive oxygen species of matrix metalloproteinase-1,3 and tissue inhibitor of matrix metalloproteinase-1 in smooth muscle cells

目的 :探讨活性氧 (ROS)对血管平滑肌细胞合成基质金属蛋白酶 - 1,3(MMP - 1,3)和基质金属蛋白酶抑制物 - 1(TIMP - 1)的影响 ,从而推测其是否促进动脉粥样硬化斑块的破裂。方法 :体外培养胎儿主动脉平滑肌细胞 ,加入含 10 0 μmol/L黄嘌呤 ,5U/L黄嘌呤氧化酶的无血清培养液 ,孵育 2 4h ,收集细胞上清液。用Westernblot ting方法检测浓缩后的细胞上清液中MMP - 1,3和TIMP - 1的含量。结果 :黄嘌呤 /黄嘌呤氧化酶组细胞上清液中的MMP - 1含量明显少于正常对照组 ,并且转化成活性形式 ;MMP - 3的含量明显多于正常对照组 ,并且转化成活性形式 ;TIMP - 1的含量明显少于正常对照组。结论 :ROS对MMPs-TIMPs平衡的影响很复杂 ,可能对动脉粥样硬化斑块的破裂起一定作用。

AIM: To understand whether reactive oxygen species promote the rupture of atherosclerotic plaques by regulating the balance of matrix metalloproteinase-1,3 (MMP-1,3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in smooth muscle cells. METHODS: Aortic smooth muscle cells from 4-6months-healthy abortive fetuses were incubated for 24 hours with xanthine (100 μmol/L) and xanthine oxidase (5 U/L) in vitro . MMP-1,3 and TIMP-1 in the concentrated culture media were measured by Western blotting ( n =3 independent experiments). RESULTS: Incubation with xanthine/xanthine oxdiase decreased the amount of MMP-1 in the aortic smooth muscle cells (21.2%±5.5% of the control group),and pro-MMP-1 was activated completely. Reactive oxygen species (ROS) also activated pro-MMP-3,and increased the production of MMP-3 in the aortic smooth muscle cells. On the other hand,ROS inhibited the production of TIMP-1 in the aortic smooth muscle cells. CONCLUSION: It is complicated that ROS regulates the balance of MMPs and TIMPs. ROS may contribute to matrix degradation and the rupture in the atherosclerotic plaques.