衰老大鼠动脉顺应性与凋亡相关指标变化及缬纱坦对其影响  

The Effect of Valsartan on Arterial Compliance and Indexes Associated with Apoptosis in Aging Rat

作　　者：单海燕[1] 白小涓[1] 宗志红[2] 孟小娜[2] 陈香美[3] 

机构地区：[1]中国医科大学附属第一医院循环内科 [2]中国医科大学生物化学教研室,辽宁省沈阳市110001 [3]解放军总医院肾内科全军肾病中心暨重点实验室,北京市100853

出　　处：《中国动脉硬化杂志》2007年第9期657-660,共4页Chinese Journal of Arteriosclerosis

基　　金：国家973重点基础研究发展规划项目(G2007CB507405);辽宁省教育厅高等学校科学研究项目(05L470)

摘　　要：目的探讨衰老大鼠动脉顺应性与凋亡相关指标变化及缬纱坦对其影响,为阐明血管衰老对动脉硬化诊治的重要意义。方法Wistar大鼠分为青年组、衰老组及缬纱坦组,测定血浆丙二醛、超氧化物歧化酶水平,同时采用恒速注入流体方法测定大鼠颈动脉血管的顺应性,并利用免疫组织化学染色法、反转录—聚合酶链式反应和蛋白免疫印迹法分析各组凋亡相关基因Bcl-2 mRNA及蛋白表达、半胱氨酸天门冬氨酸蛋白酶3活性变化水平。结果与衰老组相比,缬纱坦组血浆丙二醛浓度明显降低(P<0.05),超氧化物歧化酶浓度明显升高(P<0.05);颈动脉血管的顺应性增高,其中弹性面积差异有显著性(P<0.05);主动脉血管Bcl-2阳性内皮细胞百分率增高(P<0.05),半胱氨酸天门冬氨酸蛋白酶3表达降低(P<0.05);Bcl-2 mRNA及蛋白表达水平明显增高(P<0.05),半胱氨酸天门冬氨酸蛋白酶3活性水平降低(P<0.01)。结论血管衰老有其特征性生理改变,凋亡相关基因Bcl-2表达下调、半胱氨酸天门冬氨酸蛋白酶3活性增高可能是血管衰老的重要分子机制之一,缬纱坦对血管衰老有一定保护作用,为延缓血管衰老以及防治动脉硬化开辟新途径。Aim To explore the effect of valsartan on arterial compliance and indexes associated with apoptosis in aging rat and its possible action mechanism. Methods The healthy Wistar rat were divided into young group, aging group and valsartan group to detect malondialdehyde （MDA）and superoxide dismutase （SOD）level aorta plasma, and measure the compliance of rat carotid segment by constant liquid injection. Immunohistochemistry, RT-PCR and Western-Blot were used to analyze the expression of apoptosis-association genes B-ceil lymphoma/leukemia-2 （Bcl-2 ）, Cysteinylasparate specific proteinase-3 （Caspase-3）. Results Compared with the aging group, malondialdehyde concentration in valsartan group evidently declined（ P 〈 0.05）, but superoxide dismutase markedly ascended（ P 〈 0.05 ）. The carotid flexibility increased, especially flexibility area were significantly different （ P 〈 0. 05 ）. The percentage of Bcl-2 positive cell increased （ P 〈 0.05 ）, but the percentage of Caspase-3 posi- tive ceil decreased （ P 〈 0.05 ）. Bcl-2 mRNA and protein expression increased markedly （ P 〈 0.05 ）, but Caspase-3 protein expression decreased evidently （ P 〈 0.01 ）. Conclusions Vascular aging has its special physiologic function changes. One of its molecular mechanism might be associated with decreasing the expression level of Bcl-2 and increasing Caspase-3 protein. Valsartan may protect vascular from aging through up-regulating Bcl-2 gene expression and iuhibiting Caspase-3 activation.

关 键 词：内科学 血管衰老 细胞凋亡 动脉硬化 Bcl-2 半胱氨酸天门冬氨酸蛋白酶3 缬纱坦 

分 类 号：R5[医药卫生—内科学]