PDF(Pubmed)
Abstract：
We aimed to determine effects of aliskiren, a direct renin inhibitor, loaded onto polymeric nanoparticles on the (pro)renin receptor (Atp6ap2), angiotensin II type 1 receptor (Agtr1), and angiotensin-converting enzyme (ACE) gene expression in the heart of spontaneously hypertensive rats (SHR). Twelve-week-old male SHRs were divided into an untreated group and groups treated with powdered aliskiren or aliskiren-loaded nanoparticles (25 mg/kg/day). After three weeks, the accumulation of aliskiren, distribution of polymeric nanoparticles, gene expression of Atp6ap2 and Agtr1 receptors and ACE, and protein expression of NADPH oxidase along with the conjugated diene (CD) concentration were analyzed. The accumulation of aliskiren in the heart was higher in the aliskiren-loaded nanoparticle group than in the powdered group. The fluorescent signals of nanoparticles were visible in cardiomyocytes, vessel walls, and erythrocytes. Aliskiren-loaded nanoparticles decreased the gene expression of Atp6ap2 and ACE, while not affecting Agtr1. Both forms of aliskiren decreased the protein expression of NADPH oxidase, with a more pronounced effect observed in the aliskiren-loaded nanoparticle group. CD concentration was decreased only in the aliskiren-loaded nanoparticle group. We hypothesize that aliskiren-loaded nanoparticle-mediated downregulation of Atp6ap2 and ACE may contribute to a decrease in ROS generation with beneficial effects in the heart. Moreover, polymeric nanoparticles may represent a promising tool for targeted delivery of aliskiren.
摘要：
我们的目的是确定阿利吉伦的影响，一种直接的肾素抑制剂,加载到（前）肾素受体（Atp6ap2）的聚合物纳米颗粒上，血管紧张素II1型受体（Agtr1），和血管紧张素转换酶（ACE）基因在自发性高血压大鼠（SHR）心脏中的表达。将十二周大的雄性SHR分为未治疗组和使用粉状阿利吉仑或负载阿利吉仑的纳米颗粒(25mg/kg/天)治疗的组。三周后,阿利斯吉伦的积累，聚合物纳米粒子的分布，Atp6ap2和Agtr1受体的基因表达和ACE，分析了NADPH氧化酶的蛋白质表达以及共轭二烯（CD）浓度。阿利吉仑在心脏中的积累在负载阿利吉仑的纳米颗粒组中高于粉末组中。纳米粒子的荧光信号在心肌细胞中可见，血管壁,和红细胞。负载阿利基仑的纳米颗粒降低了Atp6ap2和ACE的基因表达，而不影响Agtr1。两种形式的阿利吉仑都降低了NADPH氧化酶的蛋白表达，在加载阿利吉仑的纳米颗粒组中观察到更明显的效果。CD浓度仅在负载阿利吉仑的纳米颗粒组中降低。我们假设阿利吉仑纳米颗粒介导的Atp6ap2和ACE下调可能有助于减少ROS的产生，并对心脏产生有益作用。此外，聚合物纳米颗粒可以代表用于阿利吉仑的靶向递送的有前途的工具。
