| Summary: | 博士 === 高雄醫學大學 === 醫學研究所 === 100 === Restenosis around the site of vessel injury is a common complication after angioplasty or stenting. It is believed to be due to inflammatory reactions around the site of injury that cause smooth muscle proliferation resulting in stenosis. The aim of this thesis is to investigate the effect of shock wave (SW) therapy on preventing restenosis caused by the inflammatory response and the subsequent proliferation of smooth muscle cells (SMCs) proliferation after vascular injury. We first investigate the effectiveness of SW treatment on reducing neointimal formation and the expressions of inflammatory mediators after vascular injury. The results demonstrated significant reduction in neointimal formation. SW treatment also suppressed macrophage accumulation as well as IL-18, CD40, Cx43 and TGF-βexpressions after injury. The mRNA expression of eNOS remained unchanged after SW treatment. On the other hand, SW increased the mRNA expression of IL-10. On the part of investigating the SW treatment on alleviating SMCs proliferation, the results of in vitro studies showed significant reduction in lipopolysaccharide (LPS)-induced SMCs proliferation and TLR4 expression on cell surface through SW treatment. The SW treatment also reduced the expressions of TLR4 mRNA and protein inside smooth muscle cells, thereby inactivating the downstream NFκB-p65 and p38 MAPK pathways. In vivo investigation revealed significant suppression of neointimal formation together with reduced expressions of TLR4, NFκB-p65, and MAPK-p38 in SMCs after vascular injury following SW treatment. In conclusion, our results demonstrated that SW suppressed vascular injury-induced inflammatory responses and the subsequent SMCs proliferation, suggesting its potential clinical application in the prevention of restenosis after angioplasty and stenting.
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