妊娠诱导的调节性T细胞(piTreg)对小鼠心脏移植的保护作用
发布时间:2018-04-16 16:19
本文选题:piTreg + 心脏移植 ; 参考:《浙江大学》2011年硕士论文
【摘要】:目的:探讨过继输注PiTreg/Treg对小鼠心脏移植的保护作用。 实验方法:分别以近交系健康雄性Balb/c小鼠和C57BL/6小鼠为供、受者,制备小鼠腹部异位心脏移植模型。受者于术前接受2Gy照射,术前1天静脉输注相应细胞:对照组输注200μl生理盐水;Treg组输注健康雌性C57BL/6的Treg,5x105/200μl;PiTreg组输注孕14d C57BL/6的Treg细胞(即piTreg细胞,与雄性Balb/c小鼠交配),5x105/200μ1。观察各组移植心脏的存活时间和组织病理学变化;流式分析脾脏淋巴细胞中Treg细胞比率、Foxp3的表达率变化、嵌合体形成等。 结果:(1)以40d为观察终点,Treg组和PiTreg组移植心脏存活时间均为40±0d(n=6),较对照组9.67±0.58d(n=3)明显延长,p0.01(2)术后10d,Treg组和PiTreg组的病理排斥反应较对照组显著减轻,排斥反应不明显。(3)piTreg组和Treg组两组小鼠,术后脾脏细胞均出现不同程度的嵌合体,其中piTreg组为5.48±1.04%,Treg组1.42±0.28%,p=0.029。(4)piTreg组和Treg组两组小鼠,术后脾脏中Treg/CD4+T细胞的比例、Foxp3/CD4+T细胞的比例较健康C57/BL小鼠有显著增加,其中以输注piTreg增加更显著。(5)piTreg组和Treg组两组小鼠血清中RANTES、Mig等趋化因子的含量较对照组明显降低,但两组之间(Treg组和piTreg组)差异不明显。 结论:在小鼠同种异型心脏移植模型中,过继输注piTreg/Treg细胞能有效延长移植心脏的存活时间,其机理可能是形成微嵌合体,上调外周Treg/CD4+T细胞比例、Foxp3/CD4+T细胞比例,减少血清炎症因子等。
[Abstract]:Objective: to investigate the protective effect of adoptive infusion of PiTreg/Treg on heart transplantation in mice.Methods: heterotopic abdominal heart transplantation models were established by using inbred healthy male Balb/c mice and C57BL/6 mice as donors and recipients respectively.The recipient received 2Gy irradiation before operation, and the corresponding cells were injected intravenously 1 day before operation: the control group was infused with 200 渭 l normal saline treg group, and the healthy female C57BL/6 group was infused with the Treg cells (piTreg cells) of C57BL/6 on the 14th day of gestation in the 5 x 105 / 200 渭 l Pig group of healthy female C57BL/6, and the corresponding cells were mated with male Balb/c mice by 5 x 105 / 200 渭 1.The survival time and histopathological changes of transplanted heart were observed, and the expression rate of Foxp3 and chimerism in splenic lymphocytes were analyzed by flow cytometry.Results the survival time of transplanted heart in PiTreg group and PiTreg group was 40 卤0 d, which was significantly longer than that in control group (9.67 卤0.58 d ~ 3). The pathological rejection was significantly reduced in 10 days after operation in the Treg group and the PiTreg group. The rejection was not obvious in the two groups.There were different degrees of chimerism in spleen cells after operation, including 5.48 卤1.04T cells in piTreg group and 1.42 卤0.28g group in Treg group. The ratio of Treg/CD4 T cells in the spleen of piTreg group and Treg group was significantly higher than that in healthy C57/BL mice.The levels of serum chemokines such as RANTESS-Mig in the piTreg group and Treg group were significantly lower than those in the control group, but there was no significant difference between the two groups.Conclusion: adoptive infusion of piTreg/Treg cells can effectively prolong the survival time of allogeneic heart transplantation in mice. The mechanism may be the formation of microchimerism and the up-regulation of the ratio of peripheral Treg/CD4 T cells to Foxp3 / CD4 T cells.Reduce serum inflammatory factors and so on.
【学位授予单位】:浙江大学
【学位级别】:硕士
【学位授予年份】:2011
【分类号】:R392
【共引文献】
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2 程雁;B淋巴细胞刺激因子及其受体介导系统性红斑狼疮患者B淋巴细胞活性的作用及TACI-Ig对其的影响[D];安徽医科大学;2012年
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