IL-1RA, IL-18BP FC Fusion Protein Preliminary Study For Protection Of Vein Grafts

ObjectiveTo observe the IL-1Ra, IL-18BP-Fc fusion protein for vein grafts restenosis influence.Methods48male mice,24mice to remove the inferior vena cava as donor and were killed. Theinferior vena cavas transplanted to another24mice’s the right carotid artery with the cuffmethod.24male mice randomly divided into two groups: control group and treatmentgroup, the Cuff technology to establish inferior vena cava transplanted into carotid neckvein transplantation model, the control group will notbe injection BP-Fc fusion white, thetreatment group was given10mg/kg,respectively in a week, around, eight weeks todeath,take grafts,observe the unobstructed grafts, neo--intimal proliferation, film,inflammatory factor IL-1β, IL-18and expression. Use the rest vein of cardiac artery bypassgraft by HE stain and immunohistochemistry, study the expression of Interleukin-1beta(IL-1β) and Interleukin-18(IL-18).ResultsAll24mice survived. Vein graft intimal and medial showed varying degrees ofhyperplasia. Immunohis to chemical results show，Normal venous have not obviousinflammatory cell infiltration. Vein graft have been infiltrated a large number ofMAC-2-positive monocyte-macrophage cell,the expression of the inflammatory cytokinesIL-1β and IL-18were elevated. were(9.52±1.81)%VS(0.82±0.12)%,(.31±0.91）%VS(0.69±0.06)%，all p＜0.05. In the4th weeks, the8th weeks there is still a largenumber of macrophages infiltrating high expression of cytokines,the4weeks, the8weeksof IL-1β expression were(7.01±1.21）%,(2.48±0.62)%.The transplant vein wall graduallythickening, the lumen gradually narrow; compared with the control group vein（56.15μm±4.65μm）,the1th week, the4th weeks, the8th weeks intimal thickness were markedlythickened（204.26μm±24.29μm551.83μm±35.00μm723.90μm±127.42μm，all was p＜0.05）and compared the treatment group inflammatory cells invasion embellishdecrease,endo--metrial hyperplasia significantly reduce, eight weeks after good still open.In human samples, increased expression of IL-1β and IL-18was observed in restenosis ofbypass vein graft following coronary artery bypass grafting (CABG), accompanied byinfiltration of inflammatory cells.ConclusionExpression of the inflammatory cytokines IL-1β and IL-18was elevated in vein graftsin mouse, IL-1Ra-IL18-Fc fusion protein can inhibit the vein grafts restenosis.