阿托伐他汀钙对肾性高血压大鼠骨桥蛋白的影响

Effects of atorvastatin calcium on osteopontin in renovascular hypertensive rats

目的:观察阿托伐他汀钙对肾性高血压大鼠胸主动脉重构及骨桥蛋白(osteopontin,OPN)的影响。方法:通过两肾一夹方法构建高血压大鼠模型。21只大鼠随机取7只作为对照组(n=7),剩余14只建模后随机分为高血压组(n=7)和他汀组(n=7),术后4周末开始用阿托伐他汀钙30 mg/(kg.d)连续灌胃8周。检测大鼠尾动脉收缩压(SBP)、血脂,光镜下观察血管结构变化并计算胸主动脉中层壁厚与内径之比(MT/LD),免疫组织化学法检测OPN的表达水平,荧光定量PCR检测OPN mRNA表达。结果:高血压组的SBP、MT/LD、OPN及OPN mRNA表达比对照组显著升高,高密度脂蛋白(HDL)水平显著降低。他汀组的MT/LD、OPN及OPN mRNA表达比高血压组显著降低,HDL水平显著升高。结论:高血压可导致动脉血管OPN高表达,阿托伐他汀钙可能通过抑制OPN的过度表达而改善动脉血管重构。

Objective：To investigate the effects of atorvastatin calcium on development of vascular remodeling and osteopontin（OPN） in renovascular hypertensive rats.Methods： The 2-kindey,1-clip hypertensive rats were prepared with SD rats.Twenty-one rats were randomly selected seven rats as the control group（n=7）,the remaining rats were randomly divided into hypertension group（n=7） and the statins group（n=7） after the establishment of model.Statins group was treated with atorvastatin calcium 30 mg/（kg·d） four weeks after model construction and then given through lavage for 8 consecutive weeks.All rats were evaluated for caudal systolic blood pressure（SBP） and blood lipid,microscopic changes in vascular structure and ratio of intima media thickness to lumen diameter（MT/LD） of thoracic aorta.Expressions of OPN were assessed with immunohistochemical staining,and expressions of OPN mRNA with fluorescence quantitative PCR.Results： Compared with control group,hypertension group showed significant increase in SBP,MT/LD,and the expression of OPN and OPN mRNA,and significant decrease in HDL level.As compared with hypertension group,MT/LD and the expression of OPN and OPN mRNA of statins group were significantly decreased,while its HDL level significantly increased.Conclusion： Hypertension can lead to high expression of artery OPN,atorvastatin calcium was shown to improve the development of vascular remodeling in rats,possibly associated with decreased expression of OPN.