CAJ | 학술논문

目的探讨血管内压力升高致动脉粥样硬化发生、发展的分子机制.方法对载质蛋白E基因敲除(ApoE-/-)小鼠行跨主动脉缩窄术后正常饮食,观察缩窄术上、下血管段动脉粥样硬化斑块形成情况,并应用肌动描记系统体外不同压力灌注小鼠颈动脉血管段,观察承受不同灌注压力血管段缺氧诱导因子-1α(HIF-1α)及其下游血红素氧和酶(HO-1)和活性氧的表达水平变化;免疫印迹(Western blot)检测腺苷酸活化蛋白激酶(AMPK)、磷酸化腺苷单磷酸活化蛋白激酶(p-AMPK)水平.结果 ApoE-/-小鼠正常饮食,跨主动脉缩窄术所引起的血流动力学改变,可造成缩窄上游血管段动脉粥样硬化斑块形成,而下游血管段无动脉粥样硬化斑块形成.体外高压力灌注血管段血管壁HIF-1α表达水平增高,且其下游HO-1表达水平较低压力灌注血管段增高(2.7±0.6)倍(P＜0.05);活性氧表达水平、p-AMPK水平增高(均P＜0.05).结论动脉压力导致血管壁氧张力降低,HIF-1α和AMPK途径激活是血管内压力升高致动脉粥样硬化形成的重要机制之一.
목적 탐토혈관내압력승고치동맥죽양경화발생、발전적분자궤제.방법 대재질단백E기인고제(ApoE-/-)소서행과주동맥축착술후정상음식,관찰축착술상、하혈관단동맥죽양경화반괴형성정황,병응용기동묘기계통체외불동압력관주소서경동맥혈관단,관찰승수불동관주압력혈관단결양유도인자-1α(HIF-1α)급기하유혈홍소양화매(HO-1)화활성양적표체수평변화;면역인적(Western blot)검측선감산활화단백격매(AMPK)、린산화선감단린산활화단백격매(p-AMPK)수평.결과 ApoE-/-소서정상음식,과주동맥축착술소인기적혈류동역학개변,가조성축착상유혈관단동맥죽양경화반괴형성,이하유혈관단무동맥죽양경화반괴형성.체외고압력관주혈관단혈관벽HIF-1α표체수평증고,차기하유HO-1표체수평교저압력관주혈관단증고(2.7±0.6)배(P＜0.05);활성양표체수평、p-AMPK수평증고(균P＜0.05).결론 동맥압력도치혈관벽양장력강저,HIF-1α화AMPK도경격활시혈관내압력승고치동맥죽양경화형성적중요궤제지일.
Objective To study the molecular mechanism of atherosclerosis induced by intravascular pressure.Methods Technic aortic coarctation (TAC) was performed in ApoE-/-mice (n＝8) and control littermate (n＝8) mice.HE staining was performed in the vessels upstream and downstream of the mice models.In vitro,hypoxia inducible factor-1a (HIF-1α),heme oxygenase,reactive oxygen species and phosphorylated AMP activated protein kinase (AMPK) were analyzed in different intravascular pressure with a myograph system that allowed independent variation of flow and pressure.Results After one month of TAC,ApoE/ mice in a normal chow diet developed occlusive plaque and accelerated atherosclerotic lesions exclusively in upstream high-pressure vessel segments.In vitro,HIF-1α was increased,heme oxygenase was higher over(2.7 ±0.6) fold,reactive oxygen species and phosphorylated AMPK were also enhanced in high intravascular pressure perfused vessel segments as compared with low intravascular pressure perfused vessel segments (all P＜0.05).Conclusions Intravascular pressure elevation can activate hypoxia and metabolism-associated pathways in the arterial wall,and predispose atherosclerosis accelerated.