Protective mechanism of sirolimus pretreatment against liver ischemia-reperfusion injury in rats / 中华器官移植杂志

ABSTRACT

Objective To investigate the protective effect of sirolimus pretreatment against liver ischemia-reperfusion(I/R)injury in rat model and the possible mechanism.Methods Forty-eight male SD rats were randomized into four groups (12/group)Asham group with saline,Bsham group with sirolimus,Csaline-operated group,Dsirolimus-operated group.The rats were pretreated with either saline or sirolimus (2 mg·kg~(-1)·d~(-1))by oral gavage for two weeks．The rat partial liver model of I/R injury was established,and the samples were collected at the 24th h after the I/R The serum ALT and AST levels were determined,the histologic changes were observed by HE staining under the light microscopy,the frequency of CD4~+ CD25~+ T cells among mononuclear cells in liver tissue was analyzed by using flow cytometry,the expression of Foxp3 mRNA was detected in liver tissue by real-time PCR,and the serum TGF-β,IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA).Results Serum ALT and AST levels were significantly decreased and the histological damage was significantly alleviated in the sirolimus-operated group as compared with saline-operated group(P<0.05).The percentage of CD4~+ CD25~+ T cells among mononuclear cells in groups A,B,C,and D was(6.12±1.87)%,(22.36±6.75)%,(4.53±1.02)% and(13.29±3.16)% respectively in liver tissue The expression levels of the Foxp3 mRNA were significantly higher in sirolimus group than in saline group(P<0.05).The ELISA showed that sirolimus could significantly increase the levels of TGF-β and IL-H)(P<0.05).Conclusion Pretreatment of sirolimus can effectively protect against liver ischemia-reperfusion injury in rats,which may be related to induction of CD4~+ CD25~+ Foxp3~+ T regulator cells by sirolimus,and the increase of TGF-β and IL-10 secretion to inhibit the imflammatory response.