聚乙二醇修饰载血管紧张素转化酶RNA壳聚糖纳米粒治疗高血压

Polyethylene glycol-modified chitosan nanoparticles loaded with angiotensin converting enzyme-shRNA for hypertension

BACKGROUND: Traditional antihypertensive drugs always have a short half-life period, and show unsatisfactory treatment outcomes. Chitosan, as a gene vector, can carry target genes into the designated location. Polyethylene glycol (PEG) combined with DNA to form the nanoparticles, which can provide surface protection, stabilize the nanoparticles and lengthen the nanoparticle’s half-life.OBJECTIVE: To investigate the antihypertensive effect and the histological changes of heart after PEG-modified chitosan nanoparticles loaded with angiotensin converting enzyme (ACE)-shRNA injected into the rat models of spontaneous hypertension.METHODS: There were five groups: 32 rats with hypertension were randomized into model, chitosan experimental and positive drug groups (n=8 per group); another 8 healthy rats served as controls. The rats in the model and control groups were given the injection of the same amount of normal saline via tail vein, the rats in the chitosan group received the injection of 1 mg/kg chitosan via the tail vein, those in the experiment group received the injection of 1 mg/kg PEG-modified chitosan nanoparticles loaded with ACE-shRNA, and the positive drug group rats were treated with 0.5 mg/kg benazepril hydrochloride via gastric lavage at 1 and 10 days, respectively.RESULTS AND CONCLUSION: The blood pressure in the experimental group at 3 days after treatment was significantly lower than that at 1 day (P < 0.05). Aorta, renal and cardiac biopsies showed positive for green fluoresce in the experimental group, which was consistent with the in vivo distribution of ACE. At 3 days after treatment, compared with the model group, in the experimental group, ACE mRNA expression and levels of myocardial hypertrophy-related indicators were significantly decreased, and myocardial hypertrophy was significantly improved (P < 0.05). These results revealed that PEG-modified ACE-shRNA chitosan nanoparticles can reduce the blood pressure and repair the injured heart of rat models of hypertension, which may be associated with ACE.