【摘 要】
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Background Rapamycin is an immunosuppressant drug, and rapamycin-coated stents inhibit endothelial proliferation and prevent restenosis in percutaneous coronary intervention.However, it is unclear if
【机 构】
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Department of Cardiac Surgery,Capital Medical University affiliated Beijing Anzhen Hospital,Beijing
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Background Rapamycin is an immunosuppressant drug, and rapamycin-coated stents inhibit endothelial proliferation and prevent restenosis in percutaneous coronary intervention.However, it is unclear if rapamycin could benefit patients undergoing artery bypass grafts.The objective of the present study was to investigate the effects of rapamycin released from the adventitia on intimal hyperplasia of the vein graft, using a mouse model of venous interposition graft.Methods The inferior vena cava of donor mice was used to replace the right common carotid artery of recipient mice.Rapamycin was delivered locally via Pluronic gel.Pathological and immunohistochemical studies were carried out on the grafted vein from week one to week six after operation and rapamycin application.Results 2 weeks after surgery, neointimal hyperplasia was significantly lower in the rapamycin group compared with the control group (2.1±1.6 vs.21.8±4.6 μm, P<0.05).4 weeks after surgery, adventitial cell density (2411±237 vs.6711±337 cells/μm2), and proliferation indexes of adventitia (18.6±4.8% vs.43.3±2.8%) and smooth muscle cells (17.4±3.6% vs.41.5±1.6%) were significantly lower in the rapamycin group compared with the control group (all P<0.05).In addition, lumen areas were larger in the rapamycin group compared with the control group at weeks 1 and 2 (week 1:0.69±0.01 vs.0.5±0.03μm2; week 2:0.60±0.02 vs.0.44±0.03μm2; both P<0.05).No differences were observed 6 weeks after operation.Conclusions Early venous intimal hyperplasia was delayed by rapamycin delivered locally via Pluronic gel.Rapamycin was a feasible therapeutic option for the treatment of grafted vessel disease.
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