[Preventive effect of gene therapy with pro-uk gene on the formation of intimal hyperplasia of vascular anastomotic site].

OBJECTIVES

To develop a new way to prevent vascular anastomotic sites from intimal hyperplasia, we applied medical suture which had been soaked in pN2-pro-uk plasmid solution to perform rat carotid artery end-to-end anastomosis and study the effect of gene therapy with pro-uk gene on the formation of intimal hyperplasia of vascular anastomotic sites.

METHODS

11/0 nylon medical suture which had been soaked in pN2-pro-uk plasmid solution was applied to perform rat carotid artery end to end anastomoses. The rats were randomly divided into control and treatment groups. In the control group, medical suture was soaked in the pN2 plasmid solution for 72 hours before use. In the treatment group, medical suture was soaked in the pN2-pro-uk plasmid solution. By means of Northern blot analysis, pro-urokinase activity assay, the number detection of cr-51 labelled platelets accumulating at anastomotic sites, 3H-TDR incorporation detection of anastomotic sites, pathological changes study, the following results were obtained.

RESULTS

When isolated RNA was hybridized with the radiolabeled pro-uk probe, band appeared in Northern blot analysis in the treatment group, but band could not be found in the control group. The pro-uk activity could be detected on the 2nd, 7th, 14th, 90th day in the treatment group, but could not be detected in the control group. The number of platelets accumulating at the anastomotic sites, the average intimal area and 3H-TDR incorporation of anastomotic sites were significantly fewer in the treatment group than in the control group (P < 0.01).

CONCLUSIONS

When medical suture which has been soaked in pN2-pro-uk plasmid solution is used to perform vascular anastomoses, the foreign gene can produce pro-uk at anastomotic sites and effectively prevent the formation of intimal hyperplasia. The mechanism is probably related to the decrease of platelets accumulating at anastomotic sites. This study provides a new way to prevent vascular anastomotic sites from intimal hyperplasia.