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Inhibitory Effect of Local Delivery of Colchicine on Proli feration of Vascular Intima in
﨩bjective:
The study was performed to investi ga te the inhibition of the proliferation of vascular intima and smooth
muscle cell (SMC) by colchicine (COL ) of high local concentrations at the site of vein gra ft and to investigate the cause of vein graft stenosis. Methods: An animal model of autogenous vein graft through transplanting the jugul ar vein into abdominal aorta was established in 48 rats.The rats after operation were randomly divided into 4 groups.GroupⅠwas control group (only pluronic F 127 gel without any COL). GroupⅡreceived low concentration of COL in F 127 gel ( 0.044 mg/ml). Group Ⅲ received middle concentration of COL in F 127 gel (0.22mg /ml) . Group Ⅳ received high concentration of COL in F 127 gel (0.44 mg/ml). The vein grafts were collected 14 days after operation. The ne ointimal thickness and ratio of intimal area to medial area were measured by us ing computer graph analysis system. The positive cells of proliferating cellular nuclear antigen (PCNA) were detected to indicate the degree and the cause of hy perplasia of intima and SMC. Cell suspension was fixed with alcohol(70%),dyed w ith propidium iodide (PI),and detected with flow cytometry. Flow cytometry coun ted 10 000 cells,and computed results by DNA content and ratio in total cells of each cell cycle. Results: The neointimal thickness were sig nificantly reduced in groupⅡ, group Ⅲ, and groupⅣ compared with groupⅠ(P <0.05). The ratios of intimal area to medial area significantly decreased in groupⅡ, group Ⅲ, and group Ⅳ compared with groupⅠ(P<0.05).The positiv e cells of PCNA in groupⅡ, group Ⅲ, and group Ⅳ were less than that in group Ⅰ 14 days after operation(P<0.05). The cell cycle distribution were sig nificantly different between the groups. Conclusion: Local delivery of COL has the effect on inhibition of proliferation of intima and SMC of vein graft. The COL can stop the SMC in the metaphase of cell division and r efrain the SMC from the next cell proliferation cycle. The inhibitory effect of colchicine on intima hyperplasia has dose effect relationship with its dose.
Published: August 30, 2002
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