Genistein联合小剂量他克莫司在胰腺移植排斥反应中的作用

背景:有实验表明CXCR3拮抗剂Genistein可减轻胰腺移植大鼠的急性排斥反应。目的:观察Genistein联合小剂量他克莫司在胰腺移植抗排斥反应中的作用。方法:以Wistar大鼠为供体,SD大鼠为受体,建立胰腺移植模型,随机分成5组:对照组(未进行药物治疗)、大剂量他克莫司组、小剂量他克莫司组、Genistein组、Genistein+小剂量他克莫司组。术后第7天行病理学,肝肾功能,血清中CD3+、CD4+、CD8+T淋巴细胞、干扰素γ、白细胞介素2浓度检测。结果与结论:与对照组、小剂量他克莫司组、Genistein组比较,Genistein+小剂量他克莫司组移植胰腺组织损伤减轻,淋巴细胞浸润减少,急性排斥反应减轻,血清CD3+、CD4+、CD8+T淋巴细胞明显减少,干扰素γ、白细胞介素2水平降低(P<0.05);并且避免了大剂量他克莫司对肝肾功能的损害。说明Genistein联合小剂量他克莫司能有效减轻胰腺移植急性排斥反应而不增加肝肾毒性。

Roles of Genistein combined with subtherapeutic FK506 in the rejection of pancreas transplantation

BACKGROUND:It has been demonstrated that CXCR3-inhibitor Genistein can mitigate the acute rejection of pancreas transplantation efficiently, but the effect of Genistein and FK506 has not been illustrated. OBJECTIVE:To investigate the role of CXCR3-inhibitor Genistein combined with subtherapeutic FK506 in the rejection of pancreas transplantation. METHODS:Five groups of rats underwent pancreas transplantation: the groups were untreated group;large-dose FK506 group;small-dose FK506 group;Genistein group;and Genistein+small-dose FK506 group. The grafts of three groups were harvested at day 7 after operation for histopathology. The expressions of CD3+, CD4+, CD8+ T cells in peripheral blood were assessed by FCM, and the levels of interferon gamma (IFN-γ) and interleukin 2 (IL-2) in serum were examined by ELISA. RESULTS AND CONCLUSION:The damage of graft tissue in Genistein+small-dose FK506 group significantly alleviated and the infiltration of lymphocytes decreased as compared with untreated group, small-dose FK506 group and Genistein group . It proved that the Genistein+small-dose FK506 combination-therapy could prevent the acute rejection. Genistein+small-dose FK506 combination therapy decreased the dosage of FK506 and prevented the damage effect on the recipients’ hepatic and renal functions. The number of CD3+, CD4+, CD8+ T cells in Genistein+small-dose FK506 group were much less;in addition, down-regulation of IFN-γ, IL-2 in serum were observed in Genistein+small-dose FK506 group. It was demonstrated that CXCR3-inhibitor Genistein combined with subtherapeutic FK506 could mitigate the acute rejection of pancreas transplantation efficiently and not increase hepatic and renal toxicity.