贝那普利和氯沙坦联合阻断肾素—血管紧张素系统对自发性高血压大鼠左心室重构的影响
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中央保健专项资助课题(鲁A032)


The Influence of Blocking Renin-Angiotensin System by Benazepril and Losartan on the Left Ventricular Remodeling of the Aged Spontaneously Hypertensive Rats
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    摘要:

    目的探讨贝那普利和氯沙坦单独与联合治疗对改善及逆转老龄自发性高血压大鼠左心室重构的影响。方法选55周龄Wistar京都大鼠18只,同龄自发性高血压大鼠54只,随机抽取Wistar京都大鼠和自发性高血压大鼠各6只检测,以确定左心室肥厚,其余分为Wistar京都大鼠对照组、自发性高血压大鼠对照组、贝那普利组10 mg/(kg.d)、氯沙坦组30 mg/(kg.d)及贝那普利10 mg/(kg.d)+氯沙坦15 mg/(kg.d)联合用药组。监测动脉收缩压及左心室质量指数,光镜观察心肌组织结构改变,免疫组织化学法测心肌胶原纤维表达,TUNEL末端标记法进行细胞凋亡检测。结果各药物干预组均可降低左心室质量指数(p<0.01),改善心肌组织结构的改变,降低总胶原及Ⅰ型胶原表达(p<0.01),并轻度降低Ⅲ型胶原表达,均以联合用药组更显著(p<0.01);贝那普利组心肌细胞凋亡率显著高于自发性高血压对照组(p<0.01),氯沙坦组及联合用药组心肌细胞凋亡率显著降低(p<0.01)。结论贝那普利和氯沙坦联合治疗自发性高血压大鼠对改善和逆转左心室重构优于单剂。

    Abstract:

    Aim To find out the effects of the combination of Benazepril and Losartan on improving and reversing left ventricular remodeling of the aged spontaneously hypertensive rats(SHR). Methods 18 WistarKyoto rats(WKY) and 54 SHR of 55 weeks old were chosen as the experiment animals.54 SHR were divided into 4 groups randomly: SHR-control group,SHR-Benazepril group [10mg/(kg·d)],SHR-Losartan group [30 mg/(kg·d)],SHR-Benazepril [10 mg/(kg·d)]+Losartan [15 mg/(kg·d)] group.After 12 weeks of treatment,all rats were drawn for detection,including observing systolic blood pressure(SBP) and left ventricular mass index(LVMI),myocardial pathologic changes and detecting the collagen protein level of left ventriculum by the immunohistochemical methods.TUNEL-method was used to detect the apoptosis rate of myocardial cells. Results Both SBP and LVMI of the SHR-control group were higher than those of drug-interfered groups(p<0.01). And it was the combination that can lower the LVMI most notably.Compared with the SHR-control group,pathological changes were obviously improved in all three drug-interfered groups,with the combination group being the most.The expression levels of type Ⅰ and total collagen fibers of each treatment group were lower than those of SHR-control group(p<0.01),especially for the combination group.The expression levels of type Ⅲ collagen fibers in each drug-interfered group were decreased slightly,and also with the combination group being the most(p<0.01).Compared with the SHR-control group,the apoptosis rate of Benazepril group was significantly higher(p<0.05),while that of Losartan group and the combination group were significantly lower(p<0.01). Conclusions Compared with monotherapy,the combination of Benazepril and Losartan seems more efficient in improving and reversing the aging SHR's left ventricular hypertrophy,myocardial apoptosis and myocardial fibrosis.

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刘雪平,祝玮玮,刘静静,迟翔宇,邵建华.贝那普利和氯沙坦联合阻断肾素—血管紧张素系统对自发性高血压大鼠左心室重构的影响[J].中国动脉硬化杂志,2006,14(1):4~8.

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  • 收稿日期:2005-01-03
  • 最后修改日期:2005-11-15
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