钠钾ATP酶介导信号转导与相关基因参与白血病细胞增殖凋亡的研究

Abnormal regulations of cell apoptosis play an important role in leukemia pathogenesis, the specific mechanisms of cell abnormal apoptosis have not been clarified. Studies over the past years have given us insights about that the Na-K-ATPase can combine with cardiotonic steroids(CTS) to activate multiple intracellular signal transduction pathways. The CTS/Na-K-ATPase complex can participate in cell proliferation and migration apoptosis process, which play an important role in the normal cells and tumor cells proliferation or apoptosis. This study illustrates the effects of marinobufagenin on proliferation or apoptosis in leukemia mouse models, Jhhan cells and original generation T-ALL leukemia cells. By using specific signal pathway inhibitors and RNAi to intervent the sodium pump function, we study the relevant signal pathway with the sodium pump to leukemia cell proliferation apoptosis influence out from the body, the influence of marinobufagenin with the sodium pump on leukemia cell proliferation apoptosis in the body and the expression changes of p57kip2 gene and c-myc gene. And we also study these genes and the effect factors affect the leukemia cell proliferation and apoptosis collaboratively. From the two aspects of in vivo and in vitro study， marinobufagenin combines with the Na-K-ATPase， reveal the effects on leukemia cell proliferation and these genes in leukemia pathogenesis, help to elucidate the pathogenesis of leukemia, which provides a new approach and the theory basis to improve the prevention and therapy of leukemia.

细胞凋亡的异常调节在白血病发病机制中起重要作用，但凋亡异常具体机制尚未阐明。近年研究发现钠泵可特异性结合强心甾类固醇发挥信号转导功能，参与细胞增殖迁移凋亡等过程，对正常细胞和肿瘤细胞增殖凋亡均有重要调节作用。 本课题通过构建白血病小鼠模型，研究海蟾蜍毒素对Jhhan细胞、T-ALL原代白血病细胞与动物模型白血病细胞增殖凋亡的作用，使用信号通路抑制剂和RNAi干预钠泵功能，研究离体时相关信号通路与钠泵对白血病细胞增殖凋亡的影响。研究海蟾蜍毒素与钠泵对在体白血病细胞增殖凋亡的影响。观察p57kip2基因与c-myc基因表达改变情况，研究这对基因与上述作用因素协同影响白血病细胞增殖和凋亡。从体内外两方面阐明海蟾蜍毒素与钠泵功能对白血病细胞增殖凋亡的调控作用以及这对基因在白血病发病机制中的作用，为阐明白血病发病机制提供新思路和理论依据，为进一步改善白血病的防治奠定基础。