应力导致血管平滑生长的信号转导机制

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The effect of cyclic mechanical strain on growth of rat vascular smooth muscle cells(VSMC) were examined. Cells were grown on silicone elastoner membrane subjected to cyclic strain (1HZ,14% elongation). A 24h exposure to mechanical strain increased the basal rate of thymidine incorporation by 1.5 fold vs unstrained cells.Cells subject to cyclic strain for 48h ,the basal rate of thymidine incorporation increased about 2.0 fold,and the cell number also have a dramatical growth. In addition ,the cyclic strain also effects the cell's morphology ,the shape index and dimension is significant increase,which occurred in time -dependent manner.We demonstrate that cyclic strain mediate cytoskeleton reorganization in cultured rat vascular smooth muscle cells.The microfilaments were removed to the cell mambrane ,as the time prolonged in cells exposured to cyclic strain.Meamwhile, VSMC exposured to cyclic strain for 12h we have not found the expression increase in cytoskeletal protein,but the α－actinin and paxillin have a tendenceto remove towards the mambrane .We also found the mechanical stress can cause tyrosine phosphorylation of cytoskeletal protein such as paxillin .. RGD,which can inhibits integrin attach to the extracellular matrix ,also can inhibit stress-induced proliferation,cytoskeleton reorganition and paxillin tytosine phosphorylation in vascular smooth muscle cells,but it do not effects the unstrained cells .In addition, a microfilament inhibitors,Cytochalasin B ,also can inhibits the proliferation by cyclic strain,but have not effcetsto static cultured cells .Genistein,a inhibitor of protein tyrosine kinases,which can inhibits cell growth both cyclic strained and static cultured cells.It implicate us the tyrosine phosphorylation is an important process not only in stress-induced VSMC proliferlation ,but it a significant event in the growth of static cultured cells.