【摘要】 目的探讨缬沙坦对血管损伤小鼠血管重构的影响和机制。方法雄性C57BL/6小鼠160只,采用聚乙烯套管包裹于股动脉外的方法造模。随机分为4组:正常组(n=40)、假手术组(n=40)、手术组(n=40)和缬沙坦组(n=40,术后予缬沙坦治疗)。造模14天后处死小鼠,取套管处股动脉观察血管形态学变化,并检测血管内膜和中膜面积,同时采用逆转录酶-聚合酶链式反应(PT-PCR)法检测烟酰胺腺嘌呤二核苷酸磷酸盐氧化酶[NAD(P)H氧化酶]主要亚单位p22phox、p47phox及rac-1 mRNA水平,采用光泽精化学发光法测定股动脉超氧阴离子(O2-)含量。结果各组中膜均无增厚表现,仅手术组和缬沙坦组可见内膜增厚。与正常组和假手术组相比,手术组[(370.00±2.50)μm2]与缬沙坦组[(160.11±2.41)μm2]内膜面积增大,但两组比较无显著性差异(P>0.05);与正常组和假手术组相比,手术组和缬沙坦组p22phox、p47phox及rac-1 mRNA水平均有升高;与手术组相比,缬沙坦组p22phox[(0.530±0.038)vs.(0.885±0.030)]、p47phox[(0.525±0.035)vs.(0.745±0.032)]、rac-1[(0.435±0.037)vs.(0.910±0.015)]mRNA降低,差异有统计学意义(P>0.05);缬沙坦组与手术组股动脉O2-表达均明显增高,且p22pho(r=0.994)、p47phox(r=0.985)及rac-1(r=0.990)的表达量与O2-含量间均呈正相关。结论短期应用缬沙坦可抑制损伤后血管内膜增厚、逆转血管重构,其机制可能与缬沙坦抗氧化应激作用有关。更多还原

【Abstract】 Objective To investigate the influence of valsartan on vascular remodeling in mice with vascular injury and the mechanism.MethodsThe model of vascular injury was established by applying polyethylene tubes wrapping around femoral artery in male C57BL/6 mice(n=160), and then the mice were randomly divided into normal group, sham-operation group operation group and valsartan group(with valsartan treatment), each n=40. After modeling for 14 days, the femoral artery with tube wrapping was collected for observing the changes of vascular morphology and intimal and medial areas of arteries were detected. The levels of p22phox, p47phox and rac-1 mRNA [subunits of NAD(P) H oxidase] were detected by applying reverse transcription-polymerase chain reaction(RT-PCR), and content of O2- in femoral artery was determined by using lucigenin chemiluminescence.ResultsThere was no medial thickening observed in all groups and intimal thickening observed only in operation group and valsartan group. Compared with normal group and sham-operation group, intimal area increased in operation group [(370.00±2.50) μm2] and valsartan group [(160.11±2.41) μm2] but there was no significant difference between these two groups(P>0.05). Compared with normal group and sham-operation group, the levels of p22phox, p47phox and rac-1 mRNA increased in operation group and valsartan group. Compared with operation group, the levels of p22phox [(0.530±0.038)vs.(0.885±0.030)], p47phox [(0.525±0.035)vs.(0.745±0.032)] and rac-1 mRNA [(0.435±0.037)vs.(0.910±0.015)] decreased in valsartan group(P<0.05). The expression of O2-increased significantly in valsartan group and operation group, and the expressions of p22pho(r=0.994), p47phox(r=0.985) and rac-1(r=0.990) were positively correlated to O2-content.ConclusionThe short-term administration of valsartan can inhibit the thickening of vascular intima and reverse vascular remodeling, and the mechanism may be related to the antioxidant stress effect of valsartan.更多还原