有氧运动对小鼠动脉血红素加氧酶-1表达的影响及在动脉粥样硬化形成中的作用研究

目的:探讨有氧运动对小鼠动脉血红素加氧酶-1(heme oxygenase-1,HO-1)的影响及其在抗动脉粥样硬化(atherosclerosis,AS)形成中的作用。方法:采用8周龄C57小鼠和ApoE基因敲除小鼠(ApoE-/-小鼠,饲以高脂饮食饲料建立动脉粥样硬化模型),分为ApoE-/-安静组(AC组)、ApoE-/-运动组(AE组)、C57运动组(CE组)、C57安静组(CC组)4组,每组15只。运动组进行12周中等强度跑台运动(10米/分×30→13米/分×60分,5次/周)。实验12周后安静时取材,采用HE染色、免疫组织化学方法及图像分析系统测定主动脉弓、腹主动脉、颈动脉组织解剖结构及HO-1表达。结果:CC组和CE组动脉组织结构正常。AC组主动脉多为纤维粥样硬化期病变,AE组多为脂纹脂斑早期病变。CC组主动脉无HO-1表达,CE组主动脉内皮层有HO-1表达。AC组主动脉内皮细胞和斑块可检测到HO-1大量表达,AE组比AC组表达减少。经图像分析,和AC组比,AE组主动脉弓、腹主动脉和颈动脉HO-1表达显著下降(分别为P<0.01、P<0.05、P<0.05),其中主动脉弓减少比腹主动脉、颈动脉明显。结论:有氧运动增强正常动脉的抗氧化能力(HO-1表达增加)。运动延缓AS形成中的动脉病变,可能与其降低主动脉的氧化应激水平(氧化应激标志HO-1降低)有关。这些改变均以主动脉弓表现明显。

Effects of Aerobic Exercise on the Heme Oxygenase-1 Expression of Aorta and Atherogenesis in Mice

Objective To reveal the anti-atherogenic role of aerobic exercise through the investigation of expression of heme oxygenase-1 in mice.Methods 8-week-old normal C57 mice and apolipoprotein E(ApoE) knockout C57 mice(ApoE-/-)were used as subjects.ApoE-/-mice were fed with high fat diet(containing 0.15% of cholesterol and 21% of fat) for 12 week to establish atherosclerotic model.Both normal and apolipoprotein E(ApoE)-knockout C57 mice were divided into C57 sedentary group(group CC),C57 exercise group(group CE),ApoE-/sedentary group(groups AC)and ApoE-/-exercise group(groups AE).Mice in exercise groups ran on a treadmill 5 days per week with gradually increased speed from 10m/min ×30 minutes to 13m/min×60 minutes for a total of 12 weeks.Heme oxygenase-1(HO-1) in aortic arch,abdominal aorta and carotid was observed with histological and immunohistochemical analysis.Results Histological structures in groups CC and CE were normal.Atheromatous plaques were detected in group AC.12-week aerobic exercise retarded the progression of atherosclerotic lesions(fatty streak)in group AE.Expression of HO-1 was not detected in group CC.Group CE exhibited an invisible expression of HO-1 in endothelial cells of aorta(especially aortic arch).The immunostaining of endothelial HO-1 became apparent in groups AC and AE.As compared with group AC,the relative area for HO-1 in group AE decreased significantly in aortic arch(P <0.01),abdominal aorta(P <0.05),and carotid(P <0.05).Conclusions Aerobic exercise increased the expression of HO-1 in aorta.The protective effect of aerobic exercise on histological structure in aortic arch was evident.