有氧运动改善ApoE基因缺陷小鼠NO合成抗AS机制的探讨

目的 :观察有氧运动对ApoE基因缺陷小鼠动脉粥样硬化 (AS)斑块形成、胸主动脉中诱导型NOS(iNOS)和内皮型NOS(eNOS)蛋白含量及血清NO浓度的影响 ,以期探讨有氧运动调节血脂代谢以外的抗AS机制。方法 :10周游泳运动后 ,测定ApoE基因缺陷小鼠AS斑块面积和血清NO浓度。采用免疫组织化学染色及计算机模拟图像定量分析法测定胸主动脉iNOS和eNOS的蛋白含量。常规HE染色和胸主动脉矢状面油红 -O大体染色观察。结果 :运动组ApoE基因缺陷小鼠AS斑块平均面积小于对照组 (P <0 0 1) ,NO浓度和eNOS蛋白含量显著高于对照组 (P <0 0 1) ,胸主动脉iNOS蛋白含量显著低于对照组 (P <0 0 5 ) ,血管壁及内膜损伤程度较对照组轻。结论 :有氧运动可能通过增高eNOS蛋白 ,抑制iNOS蛋白 ,提高生物活性形式的NO浓度 ,以改善血管内皮功能 ,延缓动脉粥样硬化斑块的发生发展 ,这可能属独立于血脂调节作用以外的其他抗动脉粥样硬化机制。

Regulating Synthesis of Nitric Oxide in Progression of Atherosclerotic after 10-week Aerobic Training in ApoE-deficient Mice

Objective In order to probe other possible mechanisms of aerobic tra ining in anti-atherosclerosis besides lipid-regulation, we observed the influenc e of aerobic training on the formation of atherosclerotic plaque, the concentrat ion of nitric oxide(NO) in serum, the content of inducible nitric oxidase (iN OS) and endothelial nitric oxidase (eNOS) in thoracic aorta in ApoE-deficient mi ce. Methods The atherosclerotic lesions, the serum NO, the con tent of thoracic aortic iNOS and eNOS by ABC immunohistochemical staining combin ed with computer image quantitative analysis technique on frozen sections were m easured after 10-week swimming training. Thoracic aorta Oil Red O (ORO) staining on the intima were als o analyzed. Results Compared with controls, aerobic training d elayed the plaque formation i n ApoE-deficient mice (P<0.01); the concentration of serum NO was increased (P<0.01); the content of thoracic aortic iNOS was decreased (P<0.05) and that of eNOS was increased (P<0.01);less lesions area in thoracic aort ic wall and intima was observed by gross light mic roscopic examination. Conclusions These data demonstrate that aerobic trainin g significantly increased active NO production by inhibiting iNOS expression mai nly in smooth muscle cells (SMCs) while increasing eNOS in endothelial cells. Th us, this selective regulation may contribute to the anti-inflammatory effect and prevention of the onset and development of atherosclerotic plaques in ApoE-defi cient mice, which may play an important role in the improvement of endothelial f unction and reflect a new mechanism of aerobic training on anti-atherosclerosis independent of lipid-regulation mechanism.