吡哆胺和替米沙坦对自发性高血压大鼠心肌重塑相关指标的影响

摘要

目的：：观察单用及联用吡哆胺和替米沙坦对自发性高血压大鼠（SHR）心肌重塑相关指标的影响。方法：48只22周龄雄性SHR，随机分为4组，12只/组。高血压对照组（H组）予以蒸馏水2 ml/d、替米沙坦组（T组）予以替米沙坦6 mg/（kg·d）、吡哆胺组（P组）予以吡哆胺200 mg/（kg·d）、联合干预组（TP组）予以替米沙坦6 mg/（kg·d）+吡哆胺200 mg/（kg·d）灌胃。测定干预前后大鼠尾动脉收缩压。干预16 W后，化学发光法检测血清一氧化氮（NO）、超氧化物歧化酶（SOD），酶联免疫吸附测定法检测血清晚期糖基化终末产物（AGEs），计算左心室重量指数，计算心肌胶原容积分数，实时定量聚合酶链式反应（PCR）检测心肌晚期糖基化终末产物受体（RAGE）信使核糖核酸（mRNA）表达水平。结果：与H组相比，T组、TP组收缩压下降（P <0.01），P组收缩压无明显改变（P>0.05）；与H组相比，T组、P组、TP组血清NO、SOD浓度升高（P <0.01）；与T组、P组相比，TP组血清NO浓度、SOD浓度进一步升高（P <0.05）。与H组相比，T组、P组、TP组左心室重量指数、心肌胶原容积分数降低（P <0.01）；与T组、P组相比，TP组左心室重量指数、心肌胶原容积分数进一步降低（P<0.05）。与H组（6.71±0.50） mg/L相比，T组（5.99±0.51） mg/L、P组（5.57±0.91） mg/L、TP组（5.24±0.63） mg/L血清AGEs降低（P <0.01）；与T组、P组相比,TP组血清AGEs进一步降低（P<0.05）。吡哆胺和替米沙坦两因素在左心室重量指数、心肌胶原容积分数中存在协同效应（P <0.05）。与H组（0.053±0.010）相比,T组（0.035±0.010）、P组（0.036±0.005）、TP组（0.024±0.007）RAGE mRNA表达水平降低（P <0.01）；与T组、P组相比,TP组RAGE mRNA表达水平进一步降低（P <0.05）。差异均有统计学意义。结论：吡哆胺有独立于降压因素之外的改善SHR体内氧化应激状态、改善心肌重塑相关指标的作用，联用吡哆胺和替米沙坦可以从不同途径打破氧化应激介导的AGEs-RAGE和肾素—血管紧张素系统的协同作用，进一步改善心肌重塑相关指标。%Objective: To observe the effect of pyridoxamine and telmisartan on the indexes of myocardial remodeling in spontaneous hypertensive rats (SHR). Methods: A total of 48 male SHR at 22 weeks of age were randomly divided into 4 groups:①Hypertension (H) control group, the rats received distilled water 2 ml/d,②telmisartan (T) group, the rats received telmisartan 6 mg/(kg.d),③pyridoxamine (P) group, the rats received pyridoxamine 200 mg/(kg.d),④Combination (TP) group, the rats received both telmisartan and pyridoxamine. All animals were treated for 16 weeks and the systolic blood pressure (SBP) was measured before and after treatment. After treatment, the serum levels of nitric oxide (NO) and super oxide dismutase (SOD) were examined by chemiluminescent method, advanced glycation end-products (AGEs) was detected by ELISA, left ventricular weight index and collagen volume fraction (CVF) in myocardial tissue were calculated, the mRNA expression of myocardial receptor of advanced glycation end products (RAGE) was evaluated by real time RT-PCR. Results: Compared with H group, SBP levels were decreased in T and TP groups,P<0.01, while SBP in P group stayed similar,P>0.05. Compared with H group, the serum levels of NO and SOD were increased in T, P and TP groups,P<0.01; while compared with T group and P group, the levels of NO and SOD were further increased in TP group,P<0.05. Compared with H group, left ventricular weight index and CVF were decreased in T, P and TP groups,P<0.01; while compared with T group and P group, left ventricular weight index and CVF were further decreased in TP group,P<0.05. Pyridoxamine and telmisartan had the coordinative effect on left ventricular weight index and CVF, P<0.05. The serum levels of AGEs were lower in T group (5.99 ± 0.51) mg/L, P group (5.57 ± 0.91) mg/L and TP group (5.24 ± 0.63) mg/L than that in H group, (6.71 ± 0.50) mg/L,P<0.01; while compared with T group and P group, AGEs was further decreased in TP group,P<0.05. The mRNA expressions of RAGE were reduced in T group (0.035 ± 0.010), P group (0.036 ± 0.005) and TP group (0.024 ± 0.007) than that in H group (0.053 ± 0.010),P <0.01; while compared with T group and P group, the mRNA of RAGE was further reduced in TP group, P<0.05. Conclusion: Pyridoxamine could improve the oxidative stress and the indexes of myocardial remodeling independently from decreasing blood pressure in SHR. Combined intervention of P and T may break the coordination systems between AGEs-RAGE and renin-angiotensin, therefore further improve the indexes of myocardial remodeling in SHR.