In Vitro And Animals Experiments Of SZ-21/VEGF/RAPA Mulilayer-coating Stent

Coronary heart disease is one major disease as serious threat to human health, and the treatment of this disease can be divided into three categories including drug treatment, surgical treatment and interventional therapy. The interventional therapy has become an important treatment of coronary heart disease, 95% of patients who received interventional therapy required stenting. The in-stent restenosis(IRS) reduce after the development of DES, Nevertheless, it could not completely eliminate the ISR. Recent study found that the drug-eluting stent lead to new problems, such as endothelialization delayed, late lead and very late in-stent thrombosis. Thus, the design of new drug-eluting stent to solve the problems becomes a hot topic in the field.SZ-21 is a platelet glycoprotein membrane proteinsⅡb/Ⅲa receptor antagonists, can function in the final link of platelet thrombosis, to specifically block the efficiency of platelet aggregation. VEGF is one kind that specifically act on the vascular endothelial cell growth factor, with pro-angiogenesis activity. RAPA is FDA approved for the anti-drug-eluting stents on the proliferation of drugs, because of its anti-proliferative effect of a strong and widely used. SZ-21/VEGF/RAPA multilayer-coating stent was cleverly combines all three to achieve the anti-restenotic, rapid internalization and advanced anti-thrombotic effect.This article studied the effect of SZ-21/VEGF/RAPA drug-eluting stent on cell behavior and function of HUVECs and SMCs,blood compatibility, anti-inflammatory ability in Vitro and rabbits in vivo to evaluate biocompatibility and the ability of anti-restenosis of the SZ-21/VEGF/RAPA drug-eluting stent,The main results are as follows:(1)SZ-21/VEGF/RAPA multilayer-coating stent On HUVECs. The results showed that the coating can promote HUVECs proliferation, adhesion and migration; ELISA assay HUVECs NOS and ET-1 release confirmed that the coating promoted the release of NOS but inhibition ET-1 release.(2)SZ-21/VEGF/RAPA multilayer-coating stent On SMCs. he results showed that the coating can inhibit SMCs proliferation, adhesion and migration. The cell morphology of SMCs on the coating surface changed, reducing long spindle-shaped but triangle and increasingorbicular-ovate(3)The blood compatibility of SZ-21/VEGF/RAPA multilayer-coating stent. The results show that the coating can decrease the rate of hemolysis, inhibit platelet adhesion and aggregation.and the APTT, PT, TT were remarkable prolonged, and Fbg significantly reduced.(4)To assess ability of the anti-inflammatory of SZ-21/VEGF/RAPA drug-eluting stents, the adhesion of macrophages and IL-1β, IL-6 were tested. The result confirmed that the coating can reduce adhesion of macrophages and IL-1β, and IL-6 release.(5)The animal experiment of SZ-21/VEGF/RAPA multilayer-coating stent. We implanted 316 L stainless steel stent, CS+PLLA coating stent and SZ-21/VEGF/RAPA multilayer-coating stent into rabbit carotid artery to study the thrombosis prevention and cure ISR by scanning electron microscopy observation, tissue staining, and Immunohistochemistry. The in-stent blood vessel, proximal blood vessel, distal blood vessel, serum samples and vital organs were got from the rabbits after stents implantation for 1 week,4 weeks and 12 weeks. The results showed that SZ-21/VEGF/RAPA multilayer-coating stent was safe and could effectively prevent thrombosis and in-stent restenosis in the 3-month observation period.