title: Combined use of rapamycin and leflunomide in prevention of acute cardiac allografts rejection in rats.
abstract: This study aimed to evaluate the role of combined use of rapamycin and leflunomide(Lef) on the prevention of acute allograft rejection in rats. After cardiac transplantations, rats were randomly divided into untreated group, rapamycin group, Lef group and rapamycin+Lef group. The drugs were given by gavage from day 0 to day 9 after transplantations. Graft survival time was observed. Some grafts were harvested for histopathological investigation on day 10 after transplantations. The levels of CD(4)(+) and CD(8)(+) T lymphocytes and the concentrations of interleukin 2(IL-2) and interferon (IFN)γ in peripheral blood were examined on day 10 after transplantations. At the same time, the body weight, the hepatic function, renal function and the haemoglobin of the recipients were also examined. The graft survival time of untreated group was 7.14 ± 1.07 days. Rapamycin group was 11.14 ± 1.35 days. Lef group was 11.29 ± 1.80 days. While in rapamycin+Lef group, the graft survival time was prolonged to 13.86 ± 1.57 days(P<0.05). Histological changes of the allografts in rapamycin+Lef group were much milder than either of the two single drug groups. The absolute number and the percentage of CD(4)(+) T lymphocytes in peripheral blood in rapamycin+Lef group were lower than those of rapamycin or Lef group on day 10 after transplantations(P<0.05), while the percentage of CD(8)(+) T lymphocytes in rapamycin+Lef group was higher than that of rapamycin or Lef group(P<0.05). The absolute number of CD(8)(+) T lymphocytes was not significantly different among rapamycin group, Lef group and rapamycin+Lef group. The levels of IL-2 and IFN-γ in rapamycin+Lef group were significantly lower than that of rapamycin group or Lef group(P<0.05). The body weight, the hepatic function, renal function and the haemoglobin were not significantly different among rapamycin group, Lef group and rapamycin+Lef group (P>0.05). Combined use of rapamycin and Lef had better effect on the prevention of acute cardiac allografts rejection in rats than monotherapy.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Jiabin
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zou
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.forename: Shibo
authors.initials: S
authors.lastname: Sun
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D007555:Isoxazoles / Q000097:blood / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D000077339:Leflunomide; D008099:Liver / Q000187:drug effects; D018655:Lymphocyte Count; D008297:Male; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000097:blood / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007555:Isoxazoles; D007371:Interferon-gamma; D000077339:Leflunomide; D020123:Sirolimus