胚胎期大鼠体内诱导免疫耐受应用于造血干细胞移植的研究

发布时间：2018-07-17 19:39

【摘要】： 目的:通过大鼠胚胎期体内诱导免疫耐受,预防GVHD,应用于造血干细胞移植。为克服造血干细胞移植须MHC相合这一限制性障碍奠定实验基础。方法:①胚胎期供体卵黄囊内接种受体MHC抗原。②受体大鼠经Co608.0Gy照射后,行骨髓腔内骨髓细胞移植。③移植后,观察受体大鼠一般状况,检测受体大鼠血象变化,查骨髓象,用PCR法检测受体外周血中供体来源的白细胞。④做GVHD相关病理检查,并进行皮肤移植。结果:①实验组受体大鼠移植后100天成活率为86.7%,明显高于各实验对照组,有明显统计学差异。②实验组受体大鼠照射移植后,白细胞计数明显下降,12天后回升,20天后升至正常水平;骨髓象示骨髓增生良好;用PCR法可检测到供体来源的白细胞。以上示重建血液系统成功。③组织病理学检查:实验组无GVHD现象,对照组有GVHD现象。④皮肤移植实验表明诱导耐受成功。结论:①通过大鼠体内胚胎期诱导免疫耐受,骨髓移植后大鼠生存状况良好,生存时间长,存活率高。能够重建造血免疫系统,并有效的预防造血干细胞移植后的GVHD。②大鼠胚胎期体内诱导免疫耐受,能够取代大鼠移植前MHC的配型。为克服临床造血干细胞移植须MHC配型这一限制性障碍奠定了基础。③胚胎期经卵黄囊途径接种同种异体抗原,该实验方法可行。④骨髓腔内骨髓细胞移植是一种有效的造血干细胞移植方法。
[Abstract]:Objective: to prevent GV HDD by inducing immune tolerance in rat embryonic phase, and to apply it to hematopoietic stem cell transplantation (HSCT). To overcome the restriction of MHC compatibility in hematopoietic stem cell transplantation (HSCT). Methods the recipient MHC antigen .2 receptor rats were inoculated in yolk sac at embryo stage. After irradiation with Co608.0 Gy, the general status of recipient rats was observed after transplantation of bone marrow cells in medullary cavity, and the changes of blood and bone marrow images in recipient rats were detected. The granulocytes from recipient peripheral blood were detected by PCR for GVHD related pathological examination and skin transplantation. Results the survival rate of the experimental group was 86.7 days after transplantation, which was significantly higher than that of the control group. The white blood cell count decreased significantly after 12 days and rose to normal level 20 days later. Bone marrow images showed that the bone marrow proliferated well and the donor white blood cells could be detected by PCR. The results showed that there was no GVHD phenomenon in the experimental group, and the skin grafts in the control group showed that the induced tolerance was successful. Conclusion\% 1\%\ It can reconstitute the hematopoietic immune system and effectively prevent the induction of immune tolerance in the embryonic phase of GVHD.2 rats after hematopoietic stem cell transplantation. It can replace the MHC matching before transplantation in rats. In order to overcome the restriction of MHC matching in clinical hematopoietic stem cell transplantation, the allogeneic antigen was inoculated through yolk sac at embryonic stage. This method is feasible. 4. Bone marrow cell transplantation is an effective method for hematopoietic stem cell transplantation.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R392.4

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