动脉粥样硬化早期家兔血管丝裂素活化蛋白激酶表达及氯沙坦的干预作用

为探讨血管紧张素Ⅱ受体拮抗剂对加速性动脉粥样硬化早期家兔血管增生及丝裂素活化蛋白激酶蛋白表达的影响 ,以家兔加速性动脉粥样硬化早期模型为研究对象 ,采用组织学、免疫细胞化学和生物化学方法评价加速性动脉粥样硬化早期家兔血管组织学、增殖细胞核抗原及丝裂素活化蛋白激酶蛋白表达和组织胆固醇含量的改变以及口服氯沙坦的干预效应。结果发现 ,动脉粥样硬化组血管内膜与中膜厚度比值、内膜增殖细胞核抗原阳性细胞数及丝裂素活化蛋白激酶蛋白表达均显著增加 ,氯沙坦干预组内膜与中膜厚度比值较动脉粥样硬化组显著下降 ,增殖细胞核抗原阳性细胞数明显减少 ,血管壁丝裂素活化蛋白激酶蛋白表达水平明显下降 (P均 <0 .0 0 1) ,主动脉组织胆固醇含量明显降低 (P <0 .0 5 )。结果提示 ,服用氯沙坦可明显减轻加速性动脉粥样硬化病变血管内膜增生 ,抑制血管损伤时血管壁丝裂素活化蛋白激酶蛋白表达 ,减少胆固醇在血管壁沉积 ,从而可能在预防动脉粥样硬化发生中起重要作用。

Effects of Losartan on Expression of Mitogen-Activated Protein Kinases and Vessel Proliferation in a Rabbit Model of Early Accelerated Atherosclerosis

Aim To investigate the effects of Losartan on expression of mitogen-activated protein kinases (MAPK) and vessel proliferation in a rabbit model of early accelerated atherosclerosis. Methods Aortic cholesterol content, expression of proliferation cell nuclear antigen (PCNA) and MAPK protein were detected by enzymatic analysis and immunohistochemistry. Results The ratio of vascular intimal to medial thickness, numbers of positive PCNA cells, and expression of MAPK protein in As group singnificantly increased compared with control group. There was a significant decrease in the ratio of vascular intimal to medial thickness, numbers of positive PCNA cells and expression of MAPK protein (P<0.001) in the Losartan-pretreated group. Aortic cholesterol content in the Losartan-pretreated group was significantly decreased compared with As group (P<0.05). Conclusion Losartan inhibits vascular MAPK expression, intimal proliferation and decreases cholesterol deposit in vascular walls which may play an important role in prevention of atherosclerosis.