氣球血管形成術前及後之睡眠剝奪增加老鼠頸動脈損傷後新生內膜增生-初步研究; Sleep Deprivation Before and After Balloon Angioplasty Significantly Augments Post-injury Neointimal Proliferation in Carotid Arteries of Rats – Preliminary Study

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Title:	氣球血管形成術前及後之睡眠剝奪增加老鼠頸動脈損傷後新生內膜增生-初步研究;Sleep Deprivation Before and After Balloon Angioplasty Significantly Augments Post-injury Neointimal Proliferation in Carotid Arteries of Rats – Preliminary Study
Authors:	林建亨;Chien-Heng Lin
Contributors:	中國醫藥大學：臨床醫學研究所碩士班
Keywords:	睡眠剝奪;氣球血管形成術;新生內膜增生;sleep deprivation;balloon angioplasty;neointimal proliferation
Date:	2008-07-09
Issue Date:	2009-08-12 14:23:38 (UTC+8)
Abstract:	冠狀動脈疾病可以使用冠狀動脈氣球血管形成術(percutaneous transluminal coronary angioplasty)來治療。雖然此步驟可有效擴張狹窄的血管，但也會引發血管受傷造成內皮增生並使血管再度狹窄。睡眠剝奪已被報告過會對傷口造成不良之影響；也是發生心血管疾病的危險因子。然而，睡眠剝奪會使氣球血管形成術後引發之內膜增生造成何種程度之影響，目前並不清楚。研究目的: 本研究想利用大白鼠睡眠剝奪模組與頸動脈氣球血管形成術模組來探討兩者之關聯，探討睡眠剝奪是否會造成氣球血管形成術後之血管新生內膜增生更明顯。研究方法: 故將大白鼠分組為無睡眠剝奪(C組，即對照組)、睡眠剝奪後 (A組)和睡眠剝奪前 (B組)施行頸動脈氣球血管形成術，頸動脈氣球血管形成術前及後皆睡眠剝奪(AB組)，在休息13天後，取其頸動脈血管，橫切其管徑並在電子顯微鏡下觀察，比較經睡眠剝奪和正常生理作息之大白鼠之動脈血管管徑中之血管新生內膜。將切下之血管切片做蘇木紫& 伊紅(hematoxylin and eosin)染色並以形態測定方法計算血管新生內膜及中膜的表面面積比率，分析及評估新生內膜增生的變化是否會因睡眠剝奪而增加。結果: C組有兩隻大白鼠，A組有兩隻大白鼠，B組有兩隻大白鼠，AB組有兩隻大白鼠。血管新生內膜及中膜的表面面積比率﹕C組為 0.900±0.010，A組為1.195±0.125，B組為1.435±0.045，AB組為1.725±0.021 。A組、B組、AB組的血管內膜及中膜的表面面積比率皆比C組有顯著增加，分別各增加了31.87%, 58.24%, 及 87.91%。且A組、B組的血管新生內膜及中膜的表面面積比率皆比C組有顯著低。結論: 無論是在睡眠剝奪之前或之後施行氣球血管形成術引起之新生內膜增生皆比無睡眠剝奪者明顯。而且施行氣球血管形成術前及後睡眠剝奪更引起新生內膜之增生。我們的結論是睡眠剝奪會增加氣球血管形成術後引發之新生內膜增生。 Background: Coronary artery disease can be treated with percutaneous transluminal coronary angioplasty (PTCA). Although this procedure is efficacious in opening stenotic arteries it may also cause injury and inflammation to the vessel producing neointima formation and subsequently restenosis. Sleep deprivation has major effects on early inflammatory response and may produce numerous untoward effects on cardiovascular disease and wound healing. However, whether sleep deprivation may affect injury-induced neointimal proliferation of the vessel is unknown. This preliminary study is to investigate if sleep deprivation will augment balloon angioplasty induced neointimal proliferation in carotid arteries of rats. Materials and Methods: Rats were randomly assigned to the following four groups: Group C (control group): balloon angioplasty without sleep deprivation. Group A: balloon angioplasty after 24-hours sleep deprivation. Group B: balloon angioplasty before 24-hours sleep deprivation. Group AB: 24-hours sleep deprivation before and after balloon angioplasty. Twenty four hours sleep deprivation was performed by the disc-on-water method for the rats in Group A, Group B and Group AB. Balloon injury was performed with all rats anesthetized and afterwards subjected to an injury of the right carotid artery with a 2F-Fogarty balloon catheter. The untouched left carotid artery was used as another (self) control. Thirteen days after the balloon injury, all of the rats were sacrificed and both carotid arteries were removed. The cross sections were later stained with hematoxylin and eosin (H&E) for morphometric analysis. Results: There were 2 rats in each group. The post injury neointima-to-media area ratio in Group C, Group A, Group B and Group AB were 0.90±0.01, 1.2±0.13, 1.44±0.05 and 1.73±0.02, respectively. There were 31.87%, 58.24%, and 87.91 increase in post-injury neointima-to-media area ratio in Group A, Group B and Group AB, respectively, compared with Group C (p<0.05). In addition, the post injury neointima-to-media area ratios in Group A and Group B were lower than that in Group AB (p<0.05). There were no neointimal proliferations in the left carotid artery for all groups. Conclusion: This preliminary study shows that neointimal proliferation induced by balloon angioplasty is significantly increased whether the 24-hours sleep deprivation was before and/or after balloon angioplasty of rats. In addition, sleep deprivation before and after balloon angioplasty had significantly more neointimal proliferation than sleep deprivation before or after angioplasty alone. We concluded that sleep deprivation significantly augments post-injury neointimal proliferation in carotid artery angioplasty of rats.
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