| To investigate the effect and mechanisms of WYE-354as mTOR kinase ATP struggling against skin transplantation in mice.A skin allograft and autograft models were established with BALB/c mice as the donor C57BL/6mice as the recipient.84C57BL/6mice were randomLy divided into6groups. The recipients was administrated daily oral Rapamycin(R) and injection WYE-354for two days(d) before skin graft and21d after graft. Allograft C57BL/6mice were classified five groups. Group One was without treatment(WT). Group Two was oral administration of R0.2mL, dose1mg·kg-1·d-1. Group Three was treated with low-dose WYE-354(WL). Group Four was treated with medium-dose WYE-354(WM). Group Five was treated with high-dose WYE-354(WH). All of the WYE-354treatment groups were given an injection of0.2mL. And WL, WM and WH groups were given1mg·kg-1·d-1,1.5mg·kg-1·d-1and50mg·kg-1·d-1. Then the skin graft survival in three days:The relevant factors are skin color, skin softness, with or without curling, the record time of skin graft rejection. Westen blotting was used to measure the phosphorylation levels of4E-BP1in the spleen at day3,7,11,21after skin graft. Histological stained was used to observe skin graft to biopsy at day11.Skin graft survival times of without treatment, rapamycingroup, WYE-354treatment with low dose, WYE-354treatment with medium dose and WYE-354treatment with high dose respectively were:11.25±1.1d,13.2±0.9d,13.2±0.7d,15.75±0.8d,20.00±1.0d. WT of skin graft survival time was less significant than the R, WL, WM, WH groups:R of skin graft surviva time was less significant than the WT, WM, WH. All in all, the difference was statistically significant(P<0.01). WM and WH of local lymphocytes infiltration of the skin graft. Comparatively speaking, that of WT, R, WL reduced. Phosphorylation levels of4E-BP1in the spleen was reduced in the R, WL, WM, WH and WM, WH were most in evidence.Compared with rapamycin, WTE-354is more effective in prolonging mouse skin allograft survival time. WYE-354, reduce of lymphocytes neutrophiles to skin graft infiltration. Regulation of mTOR signal transduction pathway related to protein phosphorylation levels was inhibited from WTE-354mTOR signal transduction pathway downstream of the downward effect of phosphorylation of4E-BP1than rapamycin, it could block the cell cycle. |
