State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, 361005, Xiamen, Fujian, China.
Department of Neurology, The First Affiliated Hospital of Xiamen University, 361005, Xiamen, Fujian, China.
Cell Death Dis. 2018 Mar 14;9(3):408. doi: 10.1038/s41419-018-0446-8.
The role of arsenic trioxide (AsO) in inhibiting immune rejection and prolonging islet allograft survival has been identified in islet allotransplantation. This study aims to explore the role of AsO in islet xenotransplantation and the action mechanism. The streptozotocin (STZ) was used in C57BL/6 mice to induce the type 1 diabetes mellitus (T1DM) for xenotransplantation models establishment. Donor islets were isolated by digesting. The flow cytometry (FCM) was used to analyze lymphocyte types. The blood sugar level was detected by using intraperitoneal glucose tolerance test (IPGTT). The serum level of cytokines was determined by the enzyme-linked immunosorbent assay (ELIZA). The cell proliferation was measured by MTT assay. The mRNA levels were quantified with qRT-PCR. AsO prolonged the survival of the recipient mice but had no influence on body weight. AsO protected the function of xenograft in insulin secretion and suppressed immune rejection of recipient. AsO inhibited proliferation of T lymphocyte and increased the proportion of Foxp3 regulatory T cells in recipient mice. AsO inhibited activation and promoted clonal anergy of T lymphocyte. AsO decreased total number of B cells and reduced partial antibody levels in recipient mice. AsO and leflunomide showed a synergistic effect in suppressing islet xenotransplant rejection. AsO prolongs islet xenograft survival by inhibiting cellular immune response, and increasing Foxp3 regulatory T cells, while decreasing partial antibody levels in serum.
三氧化二砷（AsO）在胰岛同种异体移植中被发现具有抑制免疫排斥和延长胰岛移植物存活的作用。本研究旨在探讨 AsO 在胰岛异种移植中的作用及其作用机制。采用链脲佐菌素（STZ）诱导 C57BL/6 小鼠建立 1 型糖尿病（T1DM）异种移植模型。通过消化法分离供体胰岛。采用流式细胞术（FCM）分析淋巴细胞类型。通过腹腔内葡萄糖耐量试验（IPGTT）检测血糖水平。采用酶联免疫吸附试验（ELIZA）测定血清细胞因子水平。MTT 法测定细胞增殖。qRT-PCR 定量检测 mRNA 水平。AsO 延长了受体小鼠的存活时间，但对体重没有影响。AsO 保护异种移植物的胰岛素分泌功能，抑制受体的免疫排斥反应。AsO 抑制 T 淋巴细胞的增殖，并增加受体小鼠中 Foxp3 调节性 T 细胞的比例。AsO 抑制 T 淋巴细胞的活化，并促进其克隆性无能。AsO 减少受体小鼠中 B 细胞的总数，并降低部分抗体水平。AsO 和来氟米特在抑制胰岛异种移植排斥方面具有协同作用。AsO 通过抑制细胞免疫反应、增加 Foxp3 调节性 T 细胞，同时降低血清中部分抗体水平，延长胰岛异种移植物的存活时间。
