Irbesartan对动脉粥样硬化血管细胞粘附分子1 mRNA表达的影响

Effects of Irbesartan on the Expression of Vascular Cell Adhesion Molecule-1 in a Rabbit model of Early Atherosclerosis

利用高脂饮食诱发兔动脉粥样硬化模型 ,观察血管紧张素Ⅱ 1型受体拮抗剂Irbesartan对早期动脉粥样硬化的影响。将纯种雄性日本大耳白兔 2 5只随机分为三组 :对照组 8只 ,高胆固醇组 8只和Irbesartan组 9只。给予 1%胆固醇饮食建立动脉粥样硬化模型并检测如下指标 :①测定血脂、血浆脂蛋白及血管紧张素Ⅱ水平 ;②测量动脉内膜最大厚度及内膜 中膜厚度比 ;③RT PCR、NorthernBlot检测组织中血管细胞粘附分子 1表达水平。结果发现 ,与对照组相比 ,Irbesartan组和高胆固醇组总胆固醇和甘油三酯水平明显升高 ;Irbesartan组主动脉内膜最大厚度及内膜 中膜厚度比较高胆固醇组明显降低 (P <0 .0 5 ) ;Irbesartan明显降低主动脉组织中血管细胞粘附分子 1在转录水平的表达 (P <0 .0 5 )。结果提示 ,血管紧张素Ⅱ 1型受体拮抗剂Irbesartan通过抑制血管细胞粘附分子 1的表达而延缓早期动脉粥样硬化病变进展。

Aim To evaluate the effect of angiotensin Ⅱ type 1 receptor antagonist Irbesartan on the expression of vascular cell adhesion molecule-1 (VCAM-1)in a rabbit model of high cholesterol diet induced atherosclerosis. Methods Twenty-five rabbits were divided into three groups: control group, high cholesterol group, Irbesartan group [50 mg/(kg·d)]. The later two groups received 1% cholesterol diet for 12 weeks to establish the early atherosclerosis model. Blood samples were collected for cholesterol assessment and angiotensin Ⅱ concentrations. The levels of expression of VCAM-1 mRNA were evaluated by RT-PCR and Northern Blot. Results There is no difference between the two high-cholesterol groups, although the cholesterol level of these groups are much higher than control group. Rabbits received Irbesartan showed reduced intimal thickness and the ratio of aortic intimal thickness to medial thickness compared with high cholesterol group (P<0.05). Irbesartan administration for 12 weeks caused a down-regulation in arterial expression of VCAM-1 normalized to GAPDH (P<0.05). Conclusion Chronic Irbesartan treatment ameliorated the severity of the early atherosclerosis lesions, possibly because of the suppression of VCAM-1 mRNA expression.