LY294002对小鼠体内调节性T细胞的影响  

Effect of LY294002 on regulatory T cells in mice

作　　者：顾冬生[1] 严鸣光[1] 罗宇维[1] 孙尔维[1] 

机构地区：[1]南方医科大学珠江医院器官移植免疫研究所,广东省广州市510282

出　　处：《中国组织工程研究与临床康复》2009年第31期6085-6088,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：广东省自然科学基金(5200513);国家自然科学基金(30872312;U0832003)~~

摘　　要：背景:研究已证实,磷酸肌醇3激酶特异性阻滞剂LY294002在体外具有剂量依赖性抑制细胞活性的作用,可以用于诱导肿瘤细胞凋亡,但LY294002对正常免疫系统的影响尚不清楚。目的:观察抗肿瘤药物LY294002对C57BL/6小鼠体内调节性T细胞的影响。设计、时间及地点:以调节性T细胞比例为观察对象,分组对比实验,于2008-08/12在广州南方医科大学珠江医院移植免疫研究所完成。材料:14只8周龄SPF级C57BL/6小鼠随机分成实验组与对照组,每组7只。LY294002购自广州英韦创津公司。方法:实验组腹腔注射LY294002溶液200μL(0.1mg),对照组给予等体积PBS。10h后后眼眶静脉从采血,并分离脾脏、胸腺,制备单细胞悬液,流式细胞术检测小鼠外周血、脾细胞和胸腺细胞中的CD4+CD25highT细胞。主要观察指标:小鼠外周血、脾细胞和胸腺细胞中CD4+CD25highT细胞的比例。结果:实验组小鼠外周血、脾脏、胸腺中CD4+CD25highT细胞比例分别为(0.787±0.036)%,(0.921±0.063)%,(1.230±0.131)%,对照组小鼠外周血、脾脏、胸腺中CD4+CD25highT细胞比例分别为(0.640±0.030)%,(0.639±0.046)%,(0.857±0.077)%,实验组和对照组比较差异有显著性意义(P<0.01,P<0.05)。结论:腹腔注射LY294002可提升小鼠体内调节性T细胞的比例,提示其有可能会抑制机体免疫反应,从而不利于治疗。BACKGROUND： It has been confirmed that the LY294002, a specific inhibitor of phosphoinositide 3-kinase, showed a dose-dependent manner in inhibiting cells activity in vitro, which can be used for inducing apoptosis of tumor cells. However, the effect of LY294002 on the normal immune system is poorly understood. OBJECTIVE： To investigate the effect of LY294002 on CD4^＋CD25^high T cells in C57BL/6 mice. DESIGN, TIME AND SETTING： Grouping control experiments with proportion of regulatory T cells as observation objects were carried out in the Institute of Transplant Immunology, Zhujiang Hospital of Southern Medical University from August to December in 2008. MATERIALS： Fourteen C57BL/6 mice with 8 weeks old were randomly assigned into experimental and control groups, with 7 animals in each group. LY294002 was purchased from Guangzhou Genewindows Biotech Company. METHODS： Mice in the experimental group were administered intraperitoneally with LY294002 200 pL （0.1 mg）, while the control mice were given same volume of sterile PBS. After 10 hours, peripheral blood was collected and splenocytes, thymocytes were prepared for cell suspension, the CD4^＋CD25^high T cells were measured by flowcytometry. MAIN OUTCOME MEASURES： The proportion of CD4^＋CD25^high T cells in blood, spleen and thymus of mice. RESULTS： The proportion of CD4^＋CD25^high T cells in peripheral blood, spleen and thymus of mice in the experimental group was （0.787±0.036）%, （0.921±0.063）%, and （1.230±0.131 ）%, respectively, which were significantly higher than that of （0.640±0.030）%, （0.639±0.046）% and （0.857±0.077）% in the control group. The difference had significance （P 〈 0.01, P 〈 0.05）. CONCLUSION： Intraperitoneal injection of LY294002 can raise the proportion of CD4^＋CD25^high T cells in mice, which suggest that it might inhibit the immune function and not fit for therapy.

关 键 词：磷酸肌醇3激酶/蛋白激酶B LY294002 调节性T细胞 

分 类 号：R318[医药卫生—生物医学工程]