CAJ | 학술논문

目的探讨信号传导蛋白和转录激活物3 (STAT3)在异种移植延迟性排斥反应(DXR)中的作用.方法构建小鼠供大鼠异种心脏移植模型,实验分为5组,空白对照组、移植组、DPP组[移植后给予STAT3磷酸化抑制剂5,15-Diphenylporphyrin (DPP)]、环孢素A(CsA)组(移植后给予CsA)、DPP+ CsA组(移植后给予DPP+ CsA),采用免疫组织化学及蛋白质印迹法检测心肌组织中磷酸化STAT3 (p-STAT3)的表达,采用实时荧光定量聚合酶链反应检测心肌组织中STAT3下游靶基因的表达,观察各组移植心的存活时间.结果随着移植时间的延长,移植心肌组织中p-STAT3的表达明显增加(P＜0.05).与移植组比较,DPP及CsA处理可明显抑制p-STAT3的表达,延长移植心的存活时间(P＜0.05),二者具有协同效应;DPP及CsA处理可显著抑制STAT3靶基因Bcl-xl、Bcl-2、Cyclin D1、C-myc及血管内皮生长因子(VEGF)的表达(P＜0.05),DPP+ CsA处理可进一步抑制各靶基因表达.结论 STAT3在异种移植心脏中持续活化,可能通过上调Bcl-xl、Bcl-2、cyclin D1、C-myc及VEGF等相关基因表达,促进血管内皮细胞的增殖,并抑制其凋亡,在内皮细胞激活及DXR的发生中发挥重要作用.
목적 탐토신호전도단백화전록격활물3 (STAT3)재이충이식연지성배척반응(DXR)중적작용.방법 구건소서공대서이충심장이식모형,실험분위5조,공백대조조、이식조、DPP조[이식후급여STAT3린산화억제제5,15-Diphenylporphyrin (DPP)]、배포소A(CsA)조(이식후급여CsA)、DPP+ CsA조(이식후급여DPP+ CsA),채용면역조직화학급단백질인적법검측심기조직중린산화STAT3 (p-STAT3)적표체,채용실시형광정량취합매련반응검측심기조직중STAT3하유파기인적표체,관찰각조이식심적존활시간.결과 수착이식시간적연장,이식심기조직중p-STAT3적표체명현증가(P＜0.05).여이식조비교,DPP급CsA처리가명현억제p-STAT3적표체,연장이식심적존활시간(P＜0.05),이자구유협동효응;DPP급CsA처리가현저억제STAT3파기인Bcl-xl、Bcl-2、Cyclin D1、C-myc급혈관내피생장인자(VEGF)적표체(P＜0.05),DPP+ CsA처리가진일보억제각파기인표체.결론 STAT3재이충이식심장중지속활화,가능통과상조Bcl-xl、Bcl-2、cyclin D1、C-myc급VEGF등상관기인표체,촉진혈관내피세포적증식,병억제기조망,재내피세포격활급DXR적발생중발휘중요작용.
Objective To evaluate the roles of signal transducer and activator of transcription 3(STAT3) played in delayed xenograft rejection.Method Mice-to-rats cardiac xenograft model was established and recipients were administrated by inhibitor of phosphorylation of STAT3,5,15-Diphenylporphyrin(DPP),and immunosuppressive agent,ciclosporin A (CsA) alone or both.The survival of graft was analyzed.Immunohistochemistry and immunoblotting were utilized to detect the phosphorylated STAT3 (p-STAT3),and real-time polymerase chain reaction was used to assess STAT3-targeted genes in grafts.Result The expression of p-STAT3 was increased significantly with the prolonged survival in grafts (P ＜ 0.05).Administration of DPP and CsA both significantly prolonged survival of the grafts (P＜0.05),and decreased the expressions of STAT3-targeted genes including Bcl-xl,Bcl-2,Cyclin D1,C-myc and VEGF (P＜0.05).DPP and CsA exerted the synergistic effects.Conclusion STAT3,which is persistently activated in cardiac xenografts,probably up-regulates downstream genes to promote proliferation and to inhibit apoptosis of endothelial cells,leading to the activation of endothelial cells and delayed xenograft rejection.