奥美沙坦酯对大鼠主动脉粥样斑块和血管钙化的干预作用

摘要

Objective:To investigate the intervention and possible mechanisms of olmesartan medoxomil on atherosclerosis of rats. Methods: Thirty 12-week-old male SD rats were randomly divided into 3 groups, including A group(normal group), B group(atherosclerosis model group), C group(olmesartan medoxomil intervention group). Rats in A group were fed with standard diet, rats in B group were fed with VitD3 for 3 days and high-fat diet, and rats in C group were fed with olmesartan medoxomil per day after VitD3 for 3 days and high-fat diet. The general state of health and body weight of rats was recorded per week. At the 0 week and 10th week, the serum samples were prepared after collecting the blood, and the serum level of fat, calcium, and high sensitivity C reactive protein(hs-CRP) were detected. At the 10th week the aorta were taken out and paraffin section were prepared. The morphology change was observed after HE stain, the calcium mineralization was observed after Von Kossa stain, and the expression of osteoprotegerin was detected after immunohistochemisty stain. Results: In contrast to model group, the rats in intervention group showed decreased atheromatous plaque and calcium mineralization at aorta wall, the serum level of total cholesterol and low density lipoprotein decreased markedly, as well as the serum level of hs-CRP and tissue expression level of osteoprotegerin at aorta wall. Conclusions: Olmesartan medoxomil, the angiotensin Ⅱreceptor blocker, could slow down the atherosclerosis process and improve the vascular calcification degree. The possible mechanism was implicated with the regulation of osteoprotegerin expression, the inhibition of inflammation response and the down-regulation of hyperlipidemia.%目的：探讨奥美沙坦酯对大鼠主动脉粥样硬化的干预作用及可能机制。方法：雄性12周龄SD大鼠30只随机分为正常组(A组)、动脉粥样硬化模型组(B组)和奥美沙坦酯干预组(C组)。 A组予标准饲料；B组予3 d 维生素D3(vitamin D3，VitD3)后予高脂饲料；C组予3 d VitD3后予高脂饲料和奥美沙坦酯。记录一般情况和每周体质量。0周和10周后分别取血制备血清样本，检测血脂、血钙、血高敏C反应蛋白水平。10周后取主动脉，常规制备石蜡切片，HE染色观察主动脉壁形态学变化，Von Kossa染色观察钙盐沉积，免疫组化染色检测骨保护素的表达。结果：与模型组相比，干预组大鼠主动脉壁粥样斑块和钙盐沉积明显减少，血总胆固醇和低密度脂蛋白水平明显降低，血高敏C反应蛋白水平明显降低，血管壁骨保护素的表达明显减少。结论：血管紧张素Ⅱ受体拮抗剂奥美沙坦酯可减缓大鼠的动脉粥样硬化过程，改善血管钙化程度，其机制可能与调控骨保护素的表达、抑制炎症反应和降低高脂血症有关。