SRT1720对DOCA盐敏感性高血压大鼠的治疗作用
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国家973项目(2013CB530604)


Therapeutic effect of SRT1720 on DOCA salt-sensitive hypertensive rats
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    摘要:

    目的:观察沉默信息调节因子2相关酶1(Sirtuin1,SIRT1)激活剂SRT1720对醋酸去氧皮质酮(DOCA)盐敏感性高血压大鼠(DHR)血压的调控作用-方法:28只SD大鼠行左肾切除后随机分为3组:对照组-模型组-SRT1720治疗组-对照组(n=8):饮自来水;模型组(n=10)和SRT1720治疗组(n=10):将200 mg/kg DOCA与硅胶制成的橡皮介质放置在大鼠两侧肩胛骨之间的皮下,并予1% NaCl饮水-SRT1720治疗组给予100 mg/(kg·d)灌胃-每周测收缩压1次-4周后处死,处死前检测中心动脉压及大鼠脉搏波速度,处死后取胸主动脉分别作HE染色观察主动脉厚度与血管口径变化-结果:模型组大鼠收缩压-中心动脉压-脉搏波速度明显增高,HE染色示血管平滑肌细胞(VSMC)明显肥大,弹力纤维层增厚,主动脉厚度显著增厚,而血管内径则明显下降-SRT1720治疗组大鼠收缩压-中心动脉压及脉搏波速度均较模型组显著下降-同时,SRT1720治疗后血管壁的病理改变明显减轻,血管平滑肌细胞肥大受到显著抑制,主动脉厚度显著下降,而血管内径明显增加-结论:SRT1720可通过抑制血管平滑肌细胞肥大,降低主动脉厚度,从而扩大血管内径,降低中心动脉压及收缩压-

    Abstract:

    Objective:To investigate the role of silent mating type information regulation 2 homolong1(SIRT1)activator SRT1720 in deoxycorticosterone acetate(DOCA)salt-sensitive hypertensive rats(DHR). Methods:A total of 28 male Sprague-Dawley rats underwent left nephrectomy were randomly divided into three groups:control group,model group,and SRT1720 treatment group. Control group(n=8):drinking water; model group(n=10)and SRT1720 treatment group (n=10):DOCA and silicone rubber medium at the concentration of 200 mg/kg was placed subcutaneously in rats on both sides of the scapula and given 1% NaCl drinking water. SRT1720 treatment group was given intragastric administration of SRT1720 for 4 weeks at the concentration of 100 mg/(kg·d). Systolic blood pressure(SBP)was measured once a week. After 4 weeks,central arterial pressure and pulse wave velocity (PWV)were monitored,and then rats were sacrificed. Thoracia aorta was taken for HE staining to observe the thickness and vascular caliber change. Results:In model group,SBP,central aortic pressure and PWV were significantly increased. HE staining showed marked vascular smooth muscle cell(VSMC)hypertrophy,and marked thickening of elastic fiber layer and aortic media,but a significantly decreasing in vessel diameter. Meanwhile,SRT1720 treatment group reversed these changes. Conclusion:SRT1720 could inhibit VSMC hypertrophy,reduce aortic media thickness,thereby expend blood vessel diameter,and reduce central arterial pressure and peripheral blood pressure in DOCA salt-sensitive hypertensive rats.

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张园园,王 璐,苗 莉,宋瑞花,林加娟,白 咪,张爱华,黄松明. SRT1720对DOCA盐敏感性高血压大鼠的治疗作用[J].南京医科大学学报(自然科学版),2016,(8):960-963

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  • 收稿日期:2016-03-27
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  • 在线发布日期: 2016-08-19
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