To investigate the molecular mechanisms underlying the effects of arsenic trioxide (As2O3) in combination with leflunomide on the hamster-to-rat heart xenotransplant.
Methods:
2
Transplantation of LVG hamster hearts to Lewis rats was performed by anastomosis of vessels in the neck using end-to-end anastomosis with a non-suture cuff technique. Four groups of recipient rats (
n
=6 in each) were treated with normal saline (control)
As
2
O
3
[5 mg/(kg•day) intraperitoneally]
leflunomide [5 mg/(kg•d) orally]
or leflunomide [5 mg/(kg•d)+As
2
O
3
[5 mg/(kg•d)] in combination. Donor hearts and/or rat spleens were harvested and analyzed 4 days after transplantation. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were performed to detect the expression of the nuclear factor erythroid-derived factor 2-related factor (Nrf2) and its target gene heme oxygenase-1 (HO-1)
Treg cell marker fork-head Box P3 (FOXP3)
apoptosis-associated proteins Bcl-2
Bax
and cleaved caspase-3. Immunohistochemical staining was used to detect the levels of inflammatory natural killer cell and macrophage infiltration
intercellular cell adhesion molecule-1 (ICAM-1) and complement C3.
Results:
2
Expression of Nrf2-ARE-HO-1 signaling pathway was upregulated in heart xenografts in rats treated with As
2
O
3
plus leflunomide compared with control rats or rats treated with either drug alone (
P
<
0.01)
and this was accompanied by an increased Treg cells in the recipient rat spleen (
P
<
0.01). In contrast
the expressions of Bax
cleaved caspase-3
ICAM-1
and complement C3
and infiltration of inflammatory cells in the xenografts were inhibited by As
2
O
3
plus leflunomide treatment (
P
<
0.01).
Conclusion:
2
Combination treatment with As
2
O
3
and leflunomide protected hamster heart-xenografts in recipient rats.
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相关机构
Department of Integrated Traditional Chinese and Western Medicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine
Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine
Department of Neurosurgery, Fujian Medical University Union Hospital
Department of Neurology, The First Hospital of Quanzhou Affiliated to Fujian Medical University