Abstract:

Objective To investigate the effects of different doses of immunodepressant cyclosporine (CsA) on the degree of acute rejection and activity of serum indoleamine 2, 3-dioxygenase (IDO) in rats with allogene heart transplantation. Methods With SD and Wistar rats as donors and recipients, respectively, rat cervical heterotopic heart transplantation models were established. Eighteen recipients were randomly divided into control group (n=6), low-dose CsA group (CsA 2 mg·kg-1·d-1, n=6) and high-dose CsA group (CsA 15 mg·kg-1·d-1, n=6). Blood samples were taken from abdominal aorta of recipients on the seventh day after transplantation, and heart transplants were harvested for histological examinations. Serum interleukin-2 (IL-2) and interferon-γ (IFN-γ) levels were detected by ELISA, serum kynurenine and tryptophan concentrations were measured by high-pressure liquid chromatography, and the ratios of kynurenine to tryptophan were calculated to estimate the IDO activity. Routine HE staining was performed on samples of heart transplants, and degree of acute rejection was determined with Stanford criteria. Results For serum IL-2 and IFN-γ levels and IDO activity, there were significant differences among groups (P＜0.05 or P＜0.01）, with control group>low-dose CsA group>high-dose CsA group. For degree of acute rejection of heart transplantation, there were significant differences among groups (P＜0.01）, with control group>low-dose CsA group>high-dose CsA group (P＜0.01）. Conclusion CsA may decrease the degree of acute rejection and serum IDO activity in rats with allogene heart transplantation in a dose-dependent manner, and the change of degree of acute rejection is consistent with that of IDO activity. Serum IDO activity may serve as a non-invasive indicator for the prediction and evaluation of acute rejection of transplantation.

Key words: cyclosporine, acute rejection, indoleamine 2, 3-dioxygenase, heart transplantation, rat