Role of alkaloid sinomenine in chronic rejection in the rat heart transplantation model

OBJECTIVE: To evaluate the possible role of alkaloid sinomenine (SIN) on chronic rejection in rat heart transplantation model. METHODS: After a brief course of cyclosporine A (CsA), DA recipients of PVG hearts were treated with placebo, SIN, CsA, or a combination of both drugs. Grafts were analyzed morphometrically and by immuno-histochemistry. Expressions of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and endothelin 1 (ET-1) were assessed by reverse transcription-polymerase chain reaction. RESULTS: Cardiac grafts of SIN-treated rats showed a mild degree of vasculopathy compared with untreated rats or CsA-treated recipients. Degree of vasculopathy was significantly reduced in rats treated with combined SIN and CsA than rats receiving either drug alone. Treatment with SIN alone did not affect gene expressions of bFGF, VEGF, and ET-1 while expressions of bFGF, VEGF, and ET-1 were significantly reduced by combined treatment with SIN and CsA. CONCLUSION: These results demonstrated a potential value of SIN, in combination with low-dose CsA to attenuate the vasculopathy in this rat model of chronic cardiac allograft rejection.