一种新的肝再生刺激因子HPPCn的克

发布时间：2018-02-16 14:52

本文关键词： 一种新的再生刺激因子 HPPCn 的克　出处：《中国人民解放军军事医学科学院》2006年硕士论文　论文类型：学位论文

【摘要】：高等哺乳动物组织再生的能力非常有限，而哺乳动物的肝脏却具有非常强大的再生能力，一般情况下，人的肝脏在受损后3天之内启动肝再生，2-3周后肝脏功能基本恢复，3-6个月后肝脏大小可恢复到与受损前一样。肝脏损伤及其再生的分子生物学机制一直是人们研究的热点课题之一。我国是一个肝病大国，肝炎、肝硬化与肝癌在我国发病率高、危害严重，患病人数在1.2亿左右，因而深入研究肝细胞损伤与再生的分子生物学机制，开发治疗肝损伤的药物，具有十分重要的社会意义。有关肝再生调控的研究已有70多年的历史，1931年Higgins等首先全面描述了大鼠部分肝切除后的再生过程，1975年Le Brecque等首次证实在哺乳期的肝脏或肝部分切除的肝脏中，存在一种特异性刺激肝细胞DNA合成的物质，命名为HSS。近30年来，国内外学者围绕肝再生的机制，，对动物源及人源的HSS作了大量深入的研究。我们实验室从上世纪80年代开始致力于肝刺激物的分离纯化研究，获得了一种对CCl_4引起的肝损伤具治疗作用的组分，命名为人肝细胞生成素(hepatopoietin，HPO)，并于1995年获得美国专利。最近，本室崔春萍博士等从新生小牛肝脏中分离得到了三个具有体外促进肝癌细胞增殖的蛋白质，Q-TOF质谱测序鉴定出其中之一是一个富亮氨酸的酸性核蛋白(Leucine-rich acidic nuclear protein，LANP)，其同源的人源体是pp32。pp32是一个多功能的酸性核蛋白，在正常组织可自我更新的细胞和肿瘤组织中都有较高水平的表达。研究发现其在细胞的信号转导、转录调控、细胞骨架动力学以及形态发生等过程中都参与作用，但体外促进肝细胞增殖方面目前没有报道。本研究为进一步验证该蛋白的促增殖活性并对其作用机理作更加深入的研究，需要在体外获得大量高纯度的活性蛋白。首先我们分别从人胎肝cDNA文库和HL-60细胞中扩增该基因，测序结果显示由HL-60细胞获得的基因与文献报道的pp32完全一致，从cDNA文库中调取的核苷酸序列与pp32不完全一致，而
[Abstract]:The ability of tissue regeneration in higher mammals is very limited, but the liver of mammals has a very strong ability to regenerate, in general, The function of liver is basically recovered after 3 to 6 months of liver injury. The molecular biological mechanism of liver injury and regeneration has always been studied. China is a large country with liver diseases, The incidence of hepatitis, liver cirrhosis and liver cancer is high in our country. The number of patients is about 120 million. Therefore, the molecular biological mechanism of liver cell injury and regeneration is deeply studied, and the medicine for treating liver injury is developed. Has very important social significance. The regulation of liver regeneration has been studied for more than 70 years. In 1931, Higgins et al described the process of partial hepatectomy in rats. In 1975, Le Brecque et al. There is a substance that specifically stimulates the synthesis of DNA in hepatocytes, named HSS.In the past 30 years, many scholars at home and abroad have focused on the mechanism of liver regeneration. In -20s, our laboratory devoted to the study of the purification of liver stimulant, and obtained a therapeutic component of liver injury induced by CCl_4. Named human hepatopoietin, hepatopoietin HPOA, and obtained a U. S. patent in 1995. In this room, Dr. Cui Chunping and others isolated from newborn calf liver three proteins with in vitro promotion of hepatoma cell proliferation were identified by Q-TOF mass spectrometry sequencing. One of them was a leucine-rich acid nucleoprotein Leucine-rich acidic nuclear protein. The source of the human body is pp32.pp32, a multifunctional acidic nucleoprotein. There is a high level of expression in self-renewal cells and tumor tissues in normal tissues. It has been found that these proteins are involved in signal transduction, transcriptional regulation, cytoskeleton dynamics and morphogenesis. However, the promotion of hepatocyte proliferation in vitro has not been reported. In order to further verify the proliferative activity of the protein and further study its mechanism, we need to obtain a large number of high purity active proteins in vitro. Firstly, we amplified the gene from human fetal liver cDNA library and HL-60 cells, respectively. The sequencing results showed that the gene obtained from HL-60 cells was completely consistent with the reported pp32, and the nucleotide sequence extracted from the cDNA library was not completely consistent with that of pp32.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R346;R575

【引证文献】