| Objective:In order to investigate the effect of local application of prostaglandin E1 (PGE1)-loaded Anke fibrin sealant on vascular intimal hyperplasia and smooth muscle cells's proliferation after balloon-induced injury to common carotid artery in rabbits. Determine an effective approach to prevent vascular restenosis after angioplasty.MethodsObserve the drug delivery effect of the self-made PGE1-loaded Anke fibrin sealant and draw its release curve. forty healthy male white rabbits were randomly divided into four groups: isolated carotid artery group (group I), injured carotid artery group (group II), injured carotid artery and Anke fibrin sealant group (group III) and injured carotid artery and PGE1-loaded Anke fibrin sealant group (group IV). Each group contained 10 rabbits. The right common carotid artery endothelial was denuded with balloon catheter, and the intima was injured. Two weeks after intervention, the models were sacrificed and defined segments were sectioned and measured by means of pathology and immunohistochemistry. The images were digitalized by computer video analysis system. Meanwhile the phenotypes of the vascular smooth muscle (VSMC) cells were observed by electron microscope.Results: ⑴PGE1 and Anke fibrin sealant had good biocompatibility. Approximately 50%, 76% and 90% of total PGE1 was released in the first 48h, 120h and 240h, respectively. The release curve showed that PGE1-loaded Anke fibrin sealant was a good drug delivery system and had a sustained releasing character with stability and effectiveness.⑵The vascular intima was smooth and monolayer endothelial cells were continuous in group I. In group II and group III, the intima became thick obviously, VSMCs displayed hyperplasia and infiltered into intima, while endothelial cells ranked orderly, the intima showed slight hyperplasia, and foaming VSMCs were rarely observed in group IV. The intimal areas, the degree of the vascular stricture, the positive expression of proliferating cell nuclear antigen (PCNA) in VSMCs and the number of synthetic VSMCs in group IV decreased significantly compared with group II and group III (all P<0.01). No significant deviation was found between group II and group III (P>0.05).Conclusion:⑴PGE1-loaded Anke fibrin sealant is a good drug delivery system and has a sustained releasing character with stability and effectiveness.⑵The rabbit model of restenosis by balloon-injured rabbit carotid artery is feasible and intimal proliferation is the main factor of restenosis.⑶PGE1 can significantly suppress the intimal hyperplasia and inhibit smooth muscle cells'proliferation in injured artery by local Anke fibrin sealant. Thus, PGE1-loaded Anke fibrin sealant may have clinical prospect in prevention and treatment of carotid artery restenosis after angioplasty. |
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