替米沙坦联合吡哆胺对自发性高血压大鼠主动脉重构的改善  

Combined use of telmisartan and pyridoxamine improved aortic remodeling in spontaneously hypertensive rats

作　　者：林帆[1] 朱鹏立[1] 孙成爱[1] 林虹[1] 余惠珍[1] 

机构地区：[1]福建省立医院老年科,福建省临床老年病研究所,福建医科大学省立临床医学院

出　　处：《心血管康复医学杂志》2014年第4期415-419,F0003,共6页Chinese Journal of Cardiovascular Rehabilitation Medicine

基　　金：福建省自然科学基金(2010J01127;2010J01120)~~

摘　　要：目的:探讨单用或联合应用替米沙坦及吡哆胺对自发性高血压大鼠(SHR)主动脉重构的影响,及其可能的机制。方法:雄性SHR 48只随机均分为高血压对照组,替米沙坦组,吡哆胺组,替米沙坦+吡哆胺联用组,取相同周龄和性别的京都Wistar大鼠为血压正常对照组。干预16周末取胸主动脉做切片分别行有关染色。计算主动脉壁厚/管腔半径比值(Tw/Rl)、管壁/管腔面积比(W/L)、中膜弹性纤维/胶原纤维面积比,检测腹主动脉有关酶、受体等的含量。结果:与高血压对照组比较,单用或联用替米沙坦和吡哆胺组均使中膜弹力纤维/胶原纤维面积比值显著升高,中膜胶原/中膜面积比均显著降低,联合用药还可显著降低Tw/Rl[(0.17±0.02)比(0.12±0.01)]、W/L[(0.29±0.03)比(0.22±0.02)]比值,P<0.05或<0.01;免疫组化显示联合用药可使SHR胸主动脉晚期糖基化终产物受体(RAGE)[(0.24±0.03)比(0.17±0.03)]、细胞外信号调节剂激酶1/2(pERK1/2)[(0.63±0.06)比(0.37±0.04)]表达明显下降(P<0.05,0.01)。荧光定量PCR显示药物治疗使烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶亚基p47phox的mRNA表达显著下降(P均<0.01),尤以联合用药组下降更为明显(P=0.001)。结论:联合应用替米沙坦和吡哆胺比单用具有更加明显的改善SHR胸主动脉重构的作用,其机制可能与其降低局部RAGE、p-ERK1/2表达,抑制NADPH氧化酶p47亚基活性有关。Objective：To explore influence of monotherapy or combined use of telmisartan and pyridoxamine on aor-tic remodeling in spontaneously hypertensive rats （SHR）and its possible mechanism.Methods：A total of 48 male SHE were randomly and equally divided into hypertension control group,telmisartan group,group,and telmisartan＋ group （combined treatment group）. Kyoto Wistar rats of the same age and gender were regarded as normal blood pressure control group （normal control group）. Thoracic aortic section were examined by related staining af-ter 16 weeks intervention to calculate the ratio of aortic wall thickness to radius of lumen （Tw/Rl）,the ratio of wall area to lumen area （W/L）,and the area ratio of media elastic fiber/collagen fiber. Concentrations of related en-zymes and receptor etc. of abdominal aortic were measured.Results：Compared with hypertension control group, there was significant rise in ratio of media elastic fiber/collagen fiber area and significant reduction in media collagen fiber/media area ratio in telmisartan group,pyridoxamine monotherapy group and combined treatment group,and there were significant decrease in Tw/Rl [（0.17±0.02）vs. （0.12±0.01）]and W/L [（0.29±0.03）vs. （0.22± 0.02）]ratios in combined treatment group,P 〈0.05 or 〈0.01;immunohistochemistry indicated that there were significant reductions in thoracic aortic receptor of advanced glycation end products （RAGE） [（0.24±0.03）vs.（0.17±0.03）]and extracellular signal-regulated kinase 1/2 （p-ERK1/2 ）expression [（0.63 ± 0.06）vs. （0.37± 0.04）]in combined treatment group,P 〈0.05,〈0.01. Fluorescence quantitative PCR indicated that medication can significantly reduce nicotinamide adenine dinucleotide phosphate （NADPH）oxidase subunit p47phox mRNA ex-pression （P 〈0.01 all）,especially in combined treatment group （P =0.001）.Conclusion：Combined use of telmis-artan and pyridoxamine is superior to the single use of either drug on improving thoracic aortic remod

关 键 词：大鼠 近交SHR 糖基化终产物 高级 吡哆胺 替米沙坦 

分 类 号：R544.1[医药卫生—心血管疾病]