探討震波治療對於減緩血管內膜損傷後所誘發之血管重塑所扮演的角色

The role of shock wave therapy in attenuating intima injury-induced vascular remodeling

邵佩琳(Pei-Lin Shao)

指導教授 ： 邱肇基

高雄醫學大學/醫學院/醫學研究所/博士(2011年)

摘要

血管壁受損處的血管再狹窄是行使氣球擴張術及植入血管支架後的副作用。在受損處的發炎反應及後續的平滑肌細胞增殖是造成血管再狹窄的主因。本論文的目標是利用震波治療來減少血管壁損傷後，血管處的發炎反應及後續的平滑肌細胞增生以阻止血管再狹窄的發生。本研究先觀察震波治療對於減少血管損傷後的內膜新生及發炎物質表現的效果。結果顯示，震波治療可以減少血管壁損傷後的內膜新生，同時也減少巨噬細胞聚集及IL-18、CD40、Cx43及TGF-β的表現，eNOS的表現則未改變，IL-10的表現則是增加。在探討震波治療減少平滑肌細胞增殖的部份，活體外研究結果顯示，震波治療可以減少以內毒素誘發的平滑肌細胞增殖，也抑制了平滑肌細胞表面的TLR4表現、細胞內的TLR4的訊息核糖核酸及蛋白質的表現。TLR4下游的訊息傳遞包含NFκB-p65 及P38 MAPK也受到體外震波治療而減少。動物實驗之中也發現震波治療減少內膜新生的同時，也伴隨著減少平滑肌細胞上的TLR4、NFκB-p65及P38 MAPK的表現。結論，本研究發現震波可以在血管壁損傷後，藉由減少發炎反應及後續的平滑肌細胞增生來預防血管再狹窄。因此，震波治療或許可以應用於氣球擴張術及血管支架植入後，預防血管再狹窄的新治療策略。

關鍵字

震波治療 ； 血管重塑 ； 血管再狹窄 ； 內膜新生 ； 血管損傷

並列摘要

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.

並列關鍵字

shock wave therapy ； vascular remodeling ； restenosis ； neointimal formation ； vessel injury

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