本文主要研究内容
作者杨迪（2019）在《PGRN对调节性T细胞发育及功能的影响和机制及Mst1与Mst2的共同作用对B细胞发育及BCR信号的影响和机制研究》一文中研究指出：第一部分PGRN对调节性T细胞发育及功能的影响和机制目的:探讨颗粒蛋白前体(PGRN)对调节性T细胞发育和功能的影响及分子机制。方法:在野生型和PGRN基因敲除小鼠模型中,采用流式细胞术检测小鼠中枢及外周各淋巴器官中T细胞各亚群的比例及调节性T细胞比例及其功能相关分子的表达。采用RT-PCR检测调节性T细胞中CTLA4的表达。最后采用调节性T细胞体外抑制试验验证其功能变化。结果:与野生型小鼠相比,PGRN敲除小鼠脾脏、胸腺和淋巴结中调节性T细胞的比例均升高,同时发现在脾脏调节性T细胞中CTLA4在基因转录和蛋白表达水平均显著升高。体外功能试验发现PGRN敲除小鼠的脾脏调节性T细胞的抑制功能也较野生型增强。结论:PGRN在调节性T细胞的发育和功能中扮演重要角色,其机制可能涉及CTLA4。第二部分Mst1与Mst2的共同作用对B细胞发育及BCR信号的影响和机制目的:探讨Mst1与Mst2的共同作用对B细胞发育和BCR信号的影响及其机制。方法:首先通过基因型为Mst1f/+Mst2f/f与Mst1f/+Mst2f/f CD19Cre/+小鼠之间杂交,得到基因型为Mst2f/f CD19Cre/+的Mst2条件性敲除小鼠(Mst2KO)及基因型为Mst1f/f Mst2f/f CD19Cre/+的Mst1Mst2条件性敲除小鼠(Mst1/2DKO),另外,Mst1基因敲除小鼠(Mst1KO)是复旦大学陶教授建立的背景为129 Sv Ev小鼠。在各实验小鼠模型中,采用流式细胞术检测小鼠中枢及外周B细胞发育及其各亚群比例的情况;通过Western blot及磷酸化流式细胞术检测在BCR激活的不同时间点的各信号分子的变化;利用激光共定位显微镜术检测可溶性抗原(s Ag)刺激BCR活化过程中各信号分子的变化及其与BCR的共定位情况。结果:与野生型小鼠相比,各实验小鼠模型的B细胞发育与BCR活化情况各有不同。Mst1KO小鼠B细胞发育与BCR活化存在明显障碍;Mst2KO小鼠B细胞在骨髓及脾脏的发育与BCR活化均未见明显异常;在Mst1/2DKO小鼠中则观察到B细胞发育基本正常,BCR活化的障碍较Mst1KO小鼠明显减轻。结论:Mst1与Mst2在B细胞发育和BCR活化中扮演重要角色,其中,Mst1已被证实这一过程中发挥正向调控作用,本研究探讨了Mst1KO、Mst2KO、Mst1/2DKO各小鼠模型中B细胞发育及BCR信号转导的变化,发现Mst2在这一过程中可能扮演与Mst1相反的负向调控作用。
Abstract
di yi bu fen PGRNdui diao jie xing Txi bao fa yo ji gong neng de ying xiang he ji zhi mu de :tan tao ke li dan bai qian ti (PGRN)dui diao jie xing Txi bao fa yo he gong neng de ying xiang ji fen zi ji zhi 。fang fa :zai ye sheng xing he PGRNji yin qiao chu xiao shu mo xing zhong ,cai yong liu shi xi bao shu jian ce xiao shu zhong shu ji wai zhou ge lin ba qi guan zhong Txi bao ge ya qun de bi li ji diao jie xing Txi bao bi li ji ji gong neng xiang guan fen zi de biao da 。cai yong RT-PCRjian ce diao jie xing Txi bao zhong CTLA4de biao da 。zui hou cai yong diao jie xing Txi bao ti wai yi zhi shi yan yan zheng ji gong neng bian hua 。jie guo :yu ye sheng xing xiao shu xiang bi ,PGRNqiao chu xiao shu pi zang 、xiong xian he lin ba jie zhong diao jie xing Txi bao de bi li jun sheng gao ,tong shi fa xian zai pi zang diao jie xing Txi bao zhong CTLA4zai ji yin zhuai lu he dan bai biao da shui ping jun xian zhe sheng gao 。ti wai gong neng shi yan fa xian PGRNqiao chu xiao shu de pi zang diao jie xing Txi bao de yi zhi gong neng ye jiao ye sheng xing zeng jiang 。jie lun :PGRNzai diao jie xing Txi bao de fa yo he gong neng zhong ban yan chong yao jiao se ,ji ji zhi ke neng she ji CTLA4。di er bu fen Mst1yu Mst2de gong tong zuo yong dui Bxi bao fa yo ji BCRxin hao de ying xiang he ji zhi mu de :tan tao Mst1yu Mst2de gong tong zuo yong dui Bxi bao fa yo he BCRxin hao de ying xiang ji ji ji zhi 。fang fa :shou xian tong guo ji yin xing wei Mst1f/+Mst2f/fyu Mst1f/+Mst2f/f CD19Cre/+xiao shu zhi jian za jiao ,de dao ji yin xing wei Mst2f/f CD19Cre/+de Mst2tiao jian xing qiao chu xiao shu (Mst2KO)ji ji yin xing wei Mst1f/f Mst2f/f CD19Cre/+de Mst1Mst2tiao jian xing qiao chu xiao shu (Mst1/2DKO),ling wai ,Mst1ji yin qiao chu xiao shu (Mst1KO)shi fu dan da xue tao jiao shou jian li de bei jing wei 129 Sv Evxiao shu 。zai ge shi yan xiao shu mo xing zhong ,cai yong liu shi xi bao shu jian ce xiao shu zhong shu ji wai zhou Bxi bao fa yo ji ji ge ya qun bi li de qing kuang ;tong guo Western blotji lin suan hua liu shi xi bao shu jian ce zai BCRji huo de bu tong shi jian dian de ge xin hao fen zi de bian hua ;li yong ji guang gong ding wei xian wei jing shu jian ce ke rong xing kang yuan (s Ag)ci ji BCRhuo hua guo cheng zhong ge xin hao fen zi de bian hua ji ji yu BCRde gong ding wei qing kuang 。jie guo :yu ye sheng xing xiao shu xiang bi ,ge shi yan xiao shu mo xing de Bxi bao fa yo yu BCRhuo hua qing kuang ge you bu tong 。Mst1KOxiao shu Bxi bao fa yo yu BCRhuo hua cun zai ming xian zhang ai ;Mst2KOxiao shu Bxi bao zai gu sui ji pi zang de fa yo yu BCRhuo hua jun wei jian ming xian yi chang ;zai Mst1/2DKOxiao shu zhong ze guan cha dao Bxi bao fa yo ji ben zheng chang ,BCRhuo hua de zhang ai jiao Mst1KOxiao shu ming xian jian qing 。jie lun :Mst1yu Mst2zai Bxi bao fa yo he BCRhuo hua zhong ban yan chong yao jiao se ,ji zhong ,Mst1yi bei zheng shi zhe yi guo cheng zhong fa hui zheng xiang diao kong zuo yong ,ben yan jiu tan tao le Mst1KO、Mst2KO、Mst1/2DKOge xiao shu mo xing zhong Bxi bao fa yo ji BCRxin hao zhuai dao de bian hua ,fa xian Mst2zai zhe yi guo cheng zhong ke neng ban yan yu Mst1xiang fan de fu xiang diao kong zuo yong 。
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论文作者分别是来自重庆医科大学的杨迪，发表于刊物重庆医科大学2019-09-24论文，是一篇关于颗粒蛋白前体论文,调节性细胞论文,细胞毒性淋巴细胞相关抗原论文,干扰素论文,抑制功能论文,淋巴细胞论文,信号论文,重庆医科大学2019-09-24论文的文章。本文可供学术参考使用，各位学者可以免费参考阅读下载，文章观点不代表本站观点，资料来自重庆医科大学2019-09-24论文网站，若本站收录的文献无意侵犯了您的著作版权，请联系我们删除。
标签：颗粒蛋白前体论文; 调节性细胞论文; 细胞毒性淋巴细胞相关抗原论文; 干扰素论文; 抑制功能论文; 淋巴细胞论文; 信号论文; 重庆医科大学2019-09-24论文;