课件：细胞钙信号转导与疾病细胞调亡和疾病.ppt

* ? * ? * * * ? * * * * * * * * * * * * * * * * ?? * * * * * Tumor----P53 mutation Chemicals Virus Radiation Tumor-Overexpression of Bcl2 肿瘤治疗,促进调亡, 哈医大癌灵一号(AS2O3)治疗急性早幼粒细胞白血病 生长因子与肿瘤治疗 (1)应用存活因子的单抗 (2)用糖皮质激素抑制细胞存活因子的合成, 大剂量甲基泼尼松诱导儿童急性髓性白血病. The lesion caused by attack of auto-antibody or sensitized T cell to auto-antigen(T 细胞对自身抗体的敏感) Normally, T cells against auto-antigen are eliminated by apoptosis during the development When the negative selection was deregulated (thymus diseases), The T cells survive and abnormally proliferate, then attack self tissue, lead to autoimmune diseases Autoimmune Diseases 针对自身抗原的免疫细胞未被及时清除，机体产生了针对自 身抗原的体液免疫和细胞免疫，导致器官组织损伤。 自身免疫病的MRL小鼠模型:  类似人的系统性红斑狼疮,类风湿关节炎 Fas突变 在T细胞的下游, 转入野生型的Fas cDNA, 不发生肾小球肾炎和淋巴结肿大, 自身抗体水平也大大下降. 肾小球肾炎：用Thy抗体制造模型, 注射抗体当天无细胞凋亡,第五天凋亡增多,第14天才恢复正常。 非肥胖细胞糖尿病：T细胞介导的抗胰岛β细胞的自身免疫疾病。 Rheumatoid arthritis(RA) It is caused by decreased apoptosis and increased proliferation of arthral cell Increased IL-1 and TGF-β1 and decreased Fas expression, which inhibit apoptosis Increased Bcl-2、Bcl-XL, which increased the threshold of apoptosis inhibits Fas/FasL apoptotic pathway Resistance of T-cells to apoptosis 类风湿性关节炎 病毒感染 宿主细胞诱导产生P53蛋白，TNF-α，IFN-γ，诱导细胞调亡。 病毒可能的抗调亡机制 （1）灭活p53：腺病毒 （2）高表达Bcl-2或Bcl-2样蛋白：EB病毒感染B淋巴细胞引起细胞转化，使之无限传代，与Burkitt淋巴瘤和鼻咽癌的发病有关 AIDS, Neurodegenerative diseases, cardiovascular diseases Excess in Apoptosis Acquired Immune Deficiency Syndrome（AIDS） Increased Fas gene expression HIV infection Gp120 glycoprotein expression，启动细胞死亡程序 syncytin formation,合胞素 CD4T- lymphocyte apoptosis T cell activation Cytokine：TNF↑ Tat protein-FAS AIDS AIDS是由人免疫缺陷病毒感染引起，关键发病机制是CD4淋巴细胞数量减少，与HIV感染引起的细胞凋亡有关 移植排斥反应 凋亡增加 跟免疫损害，病毒感染，药物毒性，缺血有关 Cardiovascular diseases Cell death induced by ischemia-reperfusion Apoptosis Necrosis