本文選題：異種胰島移植　切入點(diǎn)：免疫抑制　出處：《廈門大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景：糖尿病可行有效的治療方法之一是胰島移植,現(xiàn)今臨床同種免疫抑制劑得到極大發(fā)展使得部分移植患者術(shù)后長(zhǎng)期生存過上類似正常人生活,但是依然有大部分患者達(dá)不到理想免疫抑制效果并且忍受著免疫抑制劑的諸多副作用。同時(shí)供體不足限制了胰島移植的發(fā)展,異種移植就能解決這個(gè)問題。雖然異種來源的胰島細(xì)胞較充足,但異種移植面臨的排斥反應(yīng)機(jī)制非常復(fù)雜,目前對(duì)異種移植排斥都沒有得到充分的認(rèn)識(shí),限制了臨床異種移植發(fā)展的進(jìn)程。因此我們目前亟需認(rèn)識(shí)同種和異種移植的差別并開發(fā)適用于異種移植的免疫抑制劑。 方法：我們提取出Lewis大鼠胰島,然后進(jìn)行Lewis大鼠到C57BL/6小鼠腎被膜下的胰島移植。首先,我們嘗試開發(fā)中藥傳統(tǒng)藥物As2O3,研究其在異種胰島移植中的作用。其次,為了達(dá)到更理想的效果,我們把As2O3和RAPA聯(lián)合應(yīng)用于異種胰島移植,探討兩者聯(lián)合應(yīng)用效果及其機(jī)制。 結(jié)果：Lewis大鼠到C57BL/6小鼠(對(duì)照組)的胰島移植物中位生存期(median survival time, MST)為12天, As2O3組中位生存期15天,兩者比較差異有統(tǒng)計(jì)學(xué)意義(P0.05)。As203通過誘導(dǎo)脾細(xì)胞凋亡和降低血清中IFN-γ水平發(fā)揮作用。As2O3聯(lián)合RAPA中位生存期28天,而前期同種移植聯(lián)合用藥組有2/6生存期超過100天。異種移植聯(lián)合用藥效果不如同種胰島移植主要是因?yàn)楫惙N胰島移植排斥較同種胰島移植強(qiáng)烈尤其是體液免疫更為明顯。RAPA聯(lián)合As203組在排斥時(shí)間點(diǎn)IgG抗體處于高水平。 結(jié)論：As203能夠延長(zhǎng)異種胰島移植生存期；As203能夠誘導(dǎo)脾細(xì)胞凋亡、降低部分細(xì)胞免疫水平,但不能降低體液免疫水平。異種胰島移植As203聯(lián)合RAPA應(yīng)用不能對(duì)抗體液免疫反應(yīng)。
[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- 緯 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.
【學(xué)位授予單位】：廈門大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R657.5;R96

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本文編號(hào)：1573588