转化生长因子-β_2在粉防己碱对抗大鼠移植心脏慢性排斥中的作用

Effect of Tranforming Growth Factor-β_2 on Chronic Rejection of Rat Heart Transplantation Treated with Tetrandrine

目的 研究转化生长因子 -β2 (TGF -β2 )在粉防己碱 (TET)对抗移植心脏慢性排斥反应中的作用。方法 Wistar -Wistar和SD -Wister大鼠间的颈部心脏移植分别作为同系和异系对照。TET治疗组 (SD -Wistar)大鼠每日另给予 5 0mg/kgTET灌胃 ,异系对照和TET治疗组大鼠每日给予环孢素A灌胃 (1.5mg/kg) ,同系对照不用任何药物治疗。 12周后取移植心脏做组织学检查 ,免疫组织化学检测组织中TGF -β2 表达 ,以图像分析仪计算阳性率。结果 异系对照动脉管壁占血管直径的比值为 0 .64±0 .2 0 ,明显高于同系对照组 (0 .2 3±0 .0 7,P <0 .0 1)和TET治疗组(0 .3 3± 0 .11,P <0 .0 5 ) ;TGF -β2在同系对照低度表达 ,异系对照的表达明显增强 ,TET治疗组的TGF -β2 表达则明显减少。结论 TGF -β2 在慢性排斥的发生中具有重要作用 ,抑制TGF -β2 表达 ,可能是TET抗慢性排斥的作用机制之一。

Objective To investigate the role of transforming growth factor-β 2(TGF-β 2)in chronic rejection in rats after heterotopic cardiac allograft transplantation treated with tetrandrine.Methods Cervical heterotopic heart transplantation were performed both from Wistar to wistar.rats(isograft controls)and from SD to Wistar rats(allograft).TET-treated group rats were administered with TET at a dose of 50 mg/kg body weight for 12 weeks continuously.Allograft control and TET-treated groups were also treated with cyclosporine at a dosage of 1.5 mg/kg body weight.Isograft control group rats were not treated with any drug.Histological changes were monitored after 12 weeks of operation,expression of TGF-β 2 was measured by immunohistochemistry,and the percentages of positive cells were calculated with computer imaging analysis system.Results In allografts,the mean ratio of depth of vessel wall and vessel diameter was 0.64±0.20,much higher than that in isografts (0.23±0.07,P<0.01) and 50 mg TET group(0.33±0.11,P<0.05).Low-grade TGF-β 2 expressed in isograft group,enhanced expression was seen in allograft group and reduced expression in TET-treated group.Conclusion TGF-β 2 plays important role in chronic rejection,and inhibiting TGF-β 2 expression might be the major mechanism of TET in attenuating the development of chronic rejection.