Experimental Study On Genistein Prevention And Treatment Of Transplant Arteriosclerosis In Arotic Transplants Of Rat

Objective: To investigate the protective effects and potential mechanism of genistein on prevention and treatment of transplant arteriosclerosis.Methods: Male Brown-Norway to male Lewis aortic transplantation was performed. The recipients were randomly assigned four groups:(1) high-dose group(n=8): the recipients were administered with GEN at a dose of 20mg/kg body weight for 60 days continuously, (2) low-dose group(n=8): the recipients were administered with GEN at a dose of 2mg/kg body weight for 60 days continuously, (3) the dissolvent control(n=6): 0.5ml DMSO for 60 days , (4) the control(n=6): no treatment. On the sixtieth postoperative day, the graft was harvested and the blood was taken from inferior cava venae. Histological changes were monitored by HE stain. The infiltration of CD4+ and CD8+ T lymphocytes and the expression ofα- smooth muscle actin were detected by immunohistochemistry. Enzyme-labeled immunosorbent assay (ELISA) was performed for quantification of the vascular endothelial growth factor (VEGF). Results: Compared with the two controls, genistein significantly reduced the infiltration of CD4+ and CD8+ T lymphocytes and markedly prevented the proliferation and migration of VSMCs. Moreover, high dose group significantly inhibited the expression of VEGF(P<0.01), but in low group, there was no statistic difference compared with the two controls.Conclusion: The results tentatively suggest that treatment with genistein may inhibit graft arteriosclerosis. The mechanism that genistein protects transplant vessel against arteriosclerosis might involve the reduction of infiltration of inflammatory cells, down-regulation of cytokines and prevention of the proliferation and migration of VSMC. Therefore genistein might be developed to a new agent for preventing chronic allograft dysfunction.