Abstract: BACKGROUND: Ginsenoside Rg1 can reduce myocardial cell apoptosis and inflammatory response in mice with myocardial infarction, and improve cardiac function in mice. However, most previous studies used intraperitoneal injection. There are few related studies on the application of ginsenoside Rg1 in nanoparticles for myocardial infarction.
OBJECTIVE: Ginsenoside Rg1 was coated with nanoparticles to observe the effect of local application on myocardial infarction in rats.
METHODS: Ginsenoside Rg1 nanoparticles were prepared by double emulsion method. The particle size, morphology, potential, sealing rate and drug loading of the nanoparticles, as well as the sustained drug release effect in vitro were detected. Sixty-four male Sprague-Dawley rats were randomly divided into four groups (n=16). In sham operation group, only laparotomy was performed without ligation of the left anterior descending coronary artery. In the model group, ligation of left anterior descending coronary artery was conducted to make myocardial infarction model. In the medicine group, after myocardial infarction model was established, ginsenoside Rg1 was intraperitoneally injected. In the nanoparticle group, ginsenoside Rg1 nanoparticle suspension was injected into the peri-infarct area after replicating the myocardial infarction model. Echocardiogram, myocardial histology and RT-qPCR were conducted 28 days after operation. 
RESULTS AND CONCLUSION: (1) The average particle size of the ginsenoside Rg1 nanoparticles was (231.28±3.66) nm and the Zeta potential was (-24.31±3.65) mV. Transmission electron microscopy showed that the nanoparticles were spherical with a particle size of about 198 nm. The nanoparticles were evenly dispersed without agglomeration and the encapsulation efficiency of the nanoparticles was (69.82±3.21)%. The drug load was (6.05±0.02)%. The nanoparticles could release ginsenoside Rg1 for more than 30 days. (2) Echocardiogram demonstrated that compared with the sham operation group, the left ventricular function and structure of the model group were abnormal. Compared with the model group, the left ventricular function and structure were significantly improved in the medicine group and nanoparticle group; the improvement was more obvious in the nanoparticle group. (3) Hematoxylin-eosin staining and Masson staining showed that the myocardial tissue fibers of the rats in the model group were loosely arranged and irregular; the interstitial edema was accompanied by obvious congestion and inflammatory cell infiltration, and a large amount of collagen deposition was seen in and around the ischemic center. The fibers of the myocardial tissue of the rats in the medicine and nanoparticle groups were slightly loose, and the arrangement was more regular than that in the model group. The interstitial edema and inflammatory cell infiltration were less common, and the collagen deposition in and around the ischemic center was significantly reduced. Among them, the pathological improvement in the nanoparticle group was more obvious. (4) RT-qPCR detection exhibited that compared with the model group, the mRNA expression of hypoxia-inducible factor 1α, von Willebrand factor, vascular endothelial growth factor A, angiopoietin 1, connexin 43, and cadherin increased in the medicine group and nanoparticle group (P < 0.05), and the mRNA expression of tumor necrosis factor α, interleukin-1β, and interferon γ decreased (P < 0.05), and the improvement was more obvious in the nanoparticle group. (5) Local administration of ginsenoside Rg1 nanoparticles can inhibit the inflammatory response and ventricular remodeling of infarcted myocardial tissue, improve cardiac function, and promote the repair of myocardial tissue. This effect may be associated with the expression of myocardium functional proteins and genes that inhibit inflammatory factors through the promotion of vascular-related genes.

Key words: myocardial infarction, nanoparticle, ginsenoside Rg1, cardiac structure, vascularization, cardiac function