The Study Of Adventitia Applied Slow-Releasing Triptolide Inhibiting Intima Hyperplasia Of Autologous Vein Grafts Of Rabbits

Objectives: To investigate the mechanism of Triptolide inhibiting proliferation and inducing apoptosis of vascular smooth muscle cell(VSMC), thus to inhibit intima hyperplasia of the autologous vein grafts, and to investigate the feasibility of administration through vascular adventitia.Methods: Twenty-four healthy male rabbits weighted 2.0~2.5kg were randomly divided into 3 equal groups, the animal model of autologous vein graft was established through transplanting jugular vein into carotid artery. Each groups was accepted different management after vascular anastomosis being finished, blank-control group: the grafts accepted no any management; F-127 pluronic gel control group: 0.5ml F-127 pluronic gel containing 0.1ml DMSO was locally applied on the adventitia of the grafts; experiment group:0.5ml F-127 gel containing 300μg triptolide was locally applied on the adventitia. The vein grafts were harvested 2 weeks after the operation. Histomorphologic methods were used to detect the degree of intima hyperplasia of the samples. Computer image analysis system was used to measure the thickness of intima and media of the vein grafts, then calculated the degree of intima hyperplasia(thickness of intima/ thickness of media). The expression of PCNA, Bcl-2 and Fas of the samples were detected by immunohistochemistry. The apoptosis VSMCs were detected by TUNEL(terminal-deoxynucleotidyl transferase mediated nick end labeling). The variance of all the experimental data were analysised by SPSS12.0 statistics software, SNK-q test was used to compare between groups.Results: The animal model of autologous vein graft was successfully established. 2 weeks after the operation, the intima of blank and F-127 control groups thickened obviously, and their I/M ratios also increased obviously. While the intima thickness and the I/M ratio of experimental group were inhibited significantly compared with other groups (P<0.05), which were detected by histomorphologic methods and computer image analysis system. Compared with blank and F-127 control groups, the expression of PCNA and Bcl-2 of experimental group were markedly inhibited (P<0.05); while Fas was markedly increased (P<0.05). The positive cells of TUNEL also increased significantly in experimental group compared with the other 2 groups (P<0.05). There was no significant deviation between blank and F-127 control group (P>0.05).Conclusions: 1 Triptolide may inhibit the expression of PCNA and Bcl-2, enhance the expression of Fas, accordingly, inhibit the proliferation of VSMC and induce the apoptosis of VSMC. Through the two mechanisms, triptolide inhibit intima hyperplasia of the vein grafts effectively. 2 The administration route through vascular adventitia is feasible and effective.