The anti-rejection effect of berberine combined with ciclosporin A on mice with xenogenic skin / 国际中医中药杂志

ABSTRACT

Objective:To investigate the anti-rejection effect of the berberine combined with ciclosporin A (CsA) against mice with xenogenic skin transplantation and explore the mechanisms.Methods:The skin transplantation model was established by an operation, tergal skin flaps from BALB/c donor mice were transplanted to the back of C57BL/6 recipient mice. Then recipient mice were randomly divided into 5 groups ( n=20), namely sham (0.5% CMC-Na), model (0.5% CMC-Na), berberine (100 mg/kg), CsA (10 mg/kg), berberine combined with CsA (berberine 100 mg/kg and CsA 5 mg/kg). All recipient mice were intraperitoneally administered once a day for 10 days. The skin graft survival time of all mice were noted everyday. At the end of the experiment, the levels of Th1 cytokines (IL-2 and IFN-γ) and Th2 cytokines (IL-4 and IL-10) in plasma were detected by ELISA, and quantity of CD4 + CD25 + T cells were analysed by flow cytometry. Results:Compared with model group, the survival days of skin graft of those in groups treated with drugs were all significantly prolonged ( P<0.01). Berberine combined with CsA group showed a longer survival days than berberine or CsA group ( P<0.01). Compared to the model group, the content of IL-2 (11.55 ± 3.14 pg/ml vs. 19.85 ± 2.42 pg/ml), IFN-γ (26.41 ± 6.20 pg/ml vs. 57.23 ± 10.15 pg/ml) of berberine combined with ciclosporin A group significantly decreased ( P<0.05). The content of IL-4 (192.45 ± 70.12 pg/ml vs. 61.09 ± 21.61 pg/ml), IL-10 (106.79 ± 27.83 pg/ml vs. 40.08 ± 11.23 pg/ml) of berberine combined with ciclosporin A group significantly increased ( P<0.05). The amount of CD4 + CD25 + T cells (7.65% ± 2.42% vs. 3.69% ± 0.83%) in berberine combined with ciclosporin A group significantly increased ( P<0.01). Conclusions:The immunosuppressive effect of berberine combined with CsA maybe related with induction of immune tolerance, balance of Th1/Th2 cytokines and increasement of CD4 + CD25 + T cells expression.