器官移植2025，Vol.16Issue(1)：74-82,9.DOI:10.12464/j.issn.1674-7445.2024225
Stattic通过调控记忆性CD4+T细胞介导的急性排斥反应对小鼠同种异体心脏移植物存活的影响
Effect of Stattic on the survival of mouse heart allograft by regulating memory CD4+T cell-mediated acute rejection
摘要
Abstract
Objective To investigate the effect and mechanism of the signal transducer and activator of transcription 3(STAT3)inhibitor Stattic on the rejection of mouse heart allograft.Methods BALB/c mice(donors)were used to transplant skin onto C57BL/6 mice(recipients).Four weeks later,memory CD4+T cells(CD4+Tm)were isolated from the recipient mice's spleens.Mixed lymphocyte reaction experiment was conducted with C57BL/6 mouse splenocytes and CD4+Tm,and the EdU method was used to detect the effect of Stattic on CD4+Tm cell proliferation.A C57BL/6 mouse heart transplant(HTx)model was constructed,and the experiment was divided into four groups:Non-HTx group,HTx group,Tm/HTx group,and Tm/HTx+Stattic group.The survival of heart allografts in mice was observed daily.Hematoxylin-eosin staining was used to observe the histopathology of the heart allografts.Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of interferon(IFN)-γ,interleukin(IL)-2,IL-10,and transforming growth factor-β1(TGF-β1)messenger RNA(mRNA)in the heart allografts.Enzyme-linked immunosorbent assay was used to detect the levels of IFN-γ,IL-2,IL-10,and TGF-β1 in the serum.Flow cytometry was used to detect the levels of CD4+Tm(CD4+CD44+CD62L+)in splenic lymphocytes.And Western blotting was used to detect the expression levels of STAT3 and p-STAT3 proteins in the heart allografts.Results When the concentration of Stattic exceeded 2.5 μmol/L,it could inhibit the proliferation of CD4+Tm cells.Compared with the HTx group,the Tm/HTx group showed shorter survival time of heart grafts,more severe histopathological damage,increased serum IFN-γ and IL-2 levels,decreased IL-10 and TGF-β1 levels,increased relative expression of IFN-γ and IL-2 mRNA,decreased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts,increased proportion of CD4+Tm in splenic lymphocytes,and increased p-STAT3/STAT3 ratio in the heart allografts(all P<0.05).Compared with the Tm/HTx group,the Tm/HTx+Stattic group showed longer survival time of heart grafts,less severe histopathological damage,decreased serum IFN-γ and IL-2 levels,increased IL-10 and TGF-β1 levels,decreased relative expression of IFN-γ and IL-2 mRNA,increased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts,decreased proportion of CD4+Tm in splenic lymphocytes,and decreased p-STAT3/STAT3 ratio in the heart allografts(all P<0.05).Conclusions Stattic may prolong the survival time of mouse heart allografts,and its mechanism may be related to the inhibition of CD4+Tm-mediated acute rejection.关键词
心脏移植/排斥反应/信号转导和转录激活因子3/Stattic/记忆性CD4+T细胞/白细胞介素/干扰素/转化生长因子Key words
Heart transplantation/Rejection/Signal transducer and activator of transcription 3/Stattic/Memory CD4+T cell/Interleukin/Interferon/Transforming growth factor分类
医药卫生引用本文复制引用
李师亮,冯异,方明,周彦..Stattic通过调控记忆性CD4+T细胞介导的急性排斥反应对小鼠同种异体心脏移植物存活的影响[J].器官移植,2025,16(1):74-82,9.基金项目
湖北省科技创新重大专项项目(2022ACA002) （2022ACA002）
