| Objective:Sirolimus-eluting stent(SES) and paclitaxel-eluting stent(PES) are prevalently applied. The findings of multicentric, large-scale, double-blind and randomized clinical trials demonstrated a marked reduction in the incidence of restenosis, late in-stent lumen loss ,target vessel revascularization compared to bare metal stents(BMS). However,there are some potential problems,such as the drugs released from the stent delay re-endothelialization by inhibiting proliferation and migration of endothelial cells that may be the cause of late or very late stent thrombosis. To explore a new and effective drug eluting stent which can prevent in-stent thrombosis and restenosis is still a hot spot in nowadays research. To take the advantages of Chinese medicine in China, we developed a new drug eluting stent by coating triptolide.In order to reveal the mechanism of in-stent restenosis and provide theoretical fundamentals of clinical application of triptolide-eluting stent, we assess the effects of these stents on neointimal hyperplasia and the expressions of CDC2,MMP-2 in Mini-pig Coronary Artery .Methods:1. 30 Tibet mini-pigs were randomly divided into 5 groups: bare metal stent group, rapamycin-eluting group, triptolide-eluting 60μg, 100μg group and 200μg group. Each animal was implanted two same type stents in left anterior descending coronary(LAD) and right coronary artery(RCA) respectively. At 7 or 28 days, Coronary angiography was investigated before animals were sacrificed and the coronary arteries perfusion fixed.2. The stented coronary arteries were sected and the injury score, neointimal thickness above the struts and between the struts of stents were analyzed,3. The immunohistochemical staining was used to determine the protein expression of CDC2 and MMP-2. Quantitative expression of CDC2 and MMP-2 were analyzed according to the optical density.Results1. There was no significant difference in the injury scores of the BMS group (2.24±0.21), SES group (2.20±0.25), 60μg(2.11±0.24),100μg(2.18±0.22),200μg triptolide-eluting stent group(2.25±0.18)( p=0.457). To compare the BMS and 60μg triptolide eluting-stent groups with SES,100μg and 200μg triptolide-eluting stent groups, there was a significant difference in neointimal thickness above the struts and between the struts. The complete re-endothelialization were observed in all groups at 28 day.2. Immunohistochemical analysis showed that MMP-2 staining was positive in the cytoplasma of VSMC.After stent implantation 7 days and 28 days,the intensity of MMP-2 expression in 60μg triptolide eluting-stent group and BMS group were higher than in 100μg ,200μg triptolide-eluting stent group and SES group(p<0.01).3. Immunohistochemical analysis showed that CDC2 positive particles were mainly located at nuclei of SMC,and a little at cytoplasma. After stent implantation 7 days and 28 days,the intensity of CDC2 expression in 60μg triptolide-eluting stent group and BMS group were higher than in 100μg triptolide-eluting stent group and SES group(p<0.01).Conclusions1. 100μg troptolide eluting-stent group could inhibit the protein expression of MMP-2 and inhibit the migration and proliferation of vascular smooth muscle cell.2. 100μg troptolide eluting-stent could inhibit the protein expression of CDC2 and promote apoptosis of vascular smooth muscle cell.3. A local toxic reaction occured early in 200μg troptolide eluting-stent group and the latter performance was the inhibition of VSMC proliferation and neointimal hyperplasia.4. The complete re-endothelialization were observed at 28 days in all groups.100μg troptolide eluting-stent group could inhibit neointimal hyperplasia in mini-pig coronary models.
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