Department of Urology, Qianfoshan Hospital Affiliated to Shandong University, China; Transplantation Center, The First Affiliate Hospital of Wenzhou Medical University, China.
Department of Urology, Qianfoshan Hospital Affiliated to Shandong University, China; Department of Urology, The First Affiliate Hospital of Wenzhou Medical University, China.
Int Immunopharmacol. 2019 Jun;71:32-39. doi: 10.1016/j.intimp.2018.12.035. Epub 2019 Mar 13.
Chronic T cell mediated rejection (TCMR), which is characterized by infiltration of the interstitium by T cells and macrophages, still remains a major barrier to the long-term survival of kidney transplantation. Our recent report indicated that thalidomide can attenuate graft arteriosclerosis in an aortic transplant model. In this study, we investigated the effect of thalidomide on chronic TCMR in a rat model of kidney transplantation. Fischer or Lewis kidney allografts were transplanted into Lewis recipient rats. After kidney transplantation, recipient rats were divided into 3 groups: the isograft (Iso) group, allograft (Allo) group, and thalidomide (Tha) group. Rats were sacrificed at 8 weeks after kidney transplantation, and blood and kidney samples were collected. Serum concentrations of creatinine (SCr),interleukin (IL)-2, IL-6, IL-17, and TNF-α in recipients were determined, and flow cytometry was used to detect the percentages of CD4CD25, CD4 Foxp3and CD4Th17 cell subsets in the peripheral blood. Grafts were procured for histopathological examination, and the expressions of α-SMA, transforming growth-β1 (TGF-β1), and VEGF in kidney grafts were investigated using Western blot. Thalidomide treatment significantly ameliorated chronic rejection, reduced renal allograft tissue damage, and decreased serum creatinine levels. Attenuation of chronic TCMR was due to the prohibited production of inflammatory cytokines, altered distribution of the CD4 CD25 FoxP3 regulatory T (Treg) and CD4 Th17 cells in the peripheral blood, and decreased expression of TGF-β1, α-SMA, and VEGF in the kidney graft. These results demonstrated that thalidomide could effectively ameliorate chronic TCMR in a rat kidney transplant model.
慢性 T 细胞介导的排斥反应（TCMR）的特征是 T 细胞和巨噬细胞浸润间质，仍然是肾移植长期存活的主要障碍。我们最近的报告表明，沙利度胺可以在主动脉移植模型中减轻移植物动脉硬化。在这项研究中，我们研究了沙利度胺对肾移植大鼠慢性 TCMR 的影响。Fischer 或 Lewis 肾同种异体移植到 Lewis 受体大鼠中。肾移植后，受体大鼠分为 3 组：同系移植（Iso）组、同种异体移植（Allo）组和沙利度胺（Tha）组。大鼠在肾移植后 8 周处死，收集血液和肾脏样本。测定受体血清肌酐（SCr）、白细胞介素（IL）-2、IL-6、IL-17 和 TNF-α浓度，并用流式细胞术检测外周血中 CD4CD25、CD4Foxp3 和 CD4Th17 细胞亚群的百分比。获取移植物进行组织病理学检查，并用 Western blot 检测肾移植组织中α-SMA、转化生长-β1（TGF-β1）和 VEGF 的表达。沙利度胺治疗显著改善慢性排斥反应，减轻肾移植组织损伤，降低血清肌酐水平。慢性 TCMR 的减轻是由于炎症细胞因子的产生受到抑制，外周血中 CD4 CD25 FoxP3 调节性 T（Treg）和 CD4 Th17 细胞的分布发生改变，以及肾移植中 TGF-β1、α-SMA 和 VEGF 的表达降低所致。这些结果表明，沙利度胺可有效改善大鼠肾移植模型中的慢性 TCMR。
