SRT1720对DOCA盐敏感性高血压大鼠的治疗作用

Therapeutic effect of SRT1720 on DOCA salt-sensitive hypertensive rats

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%Na Cl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。

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% Na Cl 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.