三氧化二砷在异种胰岛移植中作用研究

发布时间：2018-03-06 06:00

本文选题：异种胰岛移植　切入点：免疫抑制　出处：《厦门大学》2014年硕士论文　论文类型：学位论文

【摘要】：背景：糖尿病可行有效的治疗方法之一是胰岛移植,现今临床同种免疫抑制剂得到极大发展使得部分移植患者术后长期生存过上类似正常人生活,但是依然有大部分患者达不到理想免疫抑制效果并且忍受着免疫抑制剂的诸多副作用。同时供体不足限制了胰岛移植的发展,异种移植就能解决这个问题。虽然异种来源的胰岛细胞较充足,但异种移植面临的排斥反应机制非常复杂,目前对异种移植排斥都没有得到充分的认识,限制了临床异种移植发展的进程。因此我们目前亟需认识同种和异种移植的差别并开发适用于异种移植的免疫抑制剂。方法：我们提取出Lewis大鼠胰岛,然后进行Lewis大鼠到C57BL/6小鼠肾被膜下的胰岛移植。首先,我们尝试开发中药传统药物As2O3,研究其在异种胰岛移植中的作用。其次,为了达到更理想的效果,我们把As2O3和RAPA联合应用于异种胰岛移植,探讨两者联合应用效果及其机制。结果：Lewis大鼠到C57BL/6小鼠(对照组)的胰岛移植物中位生存期(median survival time, MST)为12天, As2O3组中位生存期15天,两者比较差异有统计学意义(P0.05)。As203通过诱导脾细胞凋亡和降低血清中IFN-γ水平发挥作用。As2O3联合RAPA中位生存期28天,而前期同种移植联合用药组有2/6生存期超过100天。异种移植联合用药效果不如同种胰岛移植主要是因为异种胰岛移植排斥较同种胰岛移植强烈尤其是体液免疫更为明显。RAPA联合As203组在排斥时间点IgG抗体处于高水平。结论：As203能够延长异种胰岛移植生存期；As203能够诱导脾细胞凋亡、降低部分细胞免疫水平,但不能降低体液免疫水平。异种胰岛移植As203联合RAPA应用不能对抗体液免疫反应。
[Abstract]:Background: one of the feasible and effective treatments for diabetes mellitus is islet transplantation. But there are still many patients who do not have the ideal immunosuppressive effect and suffer from many side effects of immunosuppressive agents. At the same time, the lack of donors limits the development of islet transplantation. Xenotransplantation can solve this problem. Although islet cells from xenogeneic islets are abundant, the mechanism of rejection in xenotransplantation is very complex and has not been fully understood at present. Therefore, we urgently need to understand the difference between allograft and xenotransplantation and develop immunosuppressants suitable for xenotransplantation. Methods: we extracted islets from Lewis rats, then transplanted Lewis rats into submembranous islets of C57BL / 6 mice. Firstly, we tried to develop traditional Chinese medicine as _ 2O _ 3 to study its role in islet xenotransplantation. In order to achieve a better effect, we applied As2O3 and RAPA to islet xenotransplantation, and discussed the effect and mechanism of the combined application. Results the median survival time (MST) of islet grafts from 10 Lewis rats to C57BL / 6 mice (control group) was 12 days, while that of As2O3 group was 15 days. There was a significant difference between the two groups by inducing apoptosis of splenocytes and decreasing the level of IFN- 纬 in serum. The median survival time of P0.05N. As203 combined with RAPA was 28 days. The survival time of 2/6 days was more than 2/6 days in the pre-allograft combined group. The main reason was that the rejection of islet allograft was stronger than that of islet allograft, especially humoral immunity, and the effect of xenotransplantation combined with islet transplantation was not as good as that of islet allograft. The results showed that the level of IgG antibody was high at the time of rejection in the group of. Rapa combined with As203. Conclusion as 203 can prolong the survival time of islet xenotransplantation. As203 can induce apoptosis of splenocytes and decrease the level of cellular immunity, but it can not decrease the level of humoral immunity. As203 combined with RAPA can not antagonize humoral immune response.
【学位授予单位】：厦门大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R657.5;R96

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