發(fā)布時(shí)間：2018-02-16 14:52

  本文關(guān)鍵詞： 一種 新的 再生 刺激 因子 HPPCn 的克　出處：《中國人民解放軍軍事醫(yī)學(xué)科學(xué)院》2006年碩士論文　論文類型：學(xué)位論文

【摘要】：高等哺乳動(dòng)物組織再生的能力非常有限，而哺乳動(dòng)物的肝臟卻具有非常強(qiáng)大的再生能力，一般情況下，人的肝臟在受損后3天之內(nèi)啟動(dòng)肝再生，2-3周后肝臟功能基本恢復(fù)，3-6個(gè)月后肝臟大小可恢復(fù)到與受損前一樣。肝臟損傷及其再生的分子生物學(xué)機(jī)制一直是人們研究的熱點(diǎn)課題之一。我國是一個(gè)肝病大國，肝炎、肝硬化與肝癌在我國發(fā)病率高、危害嚴(yán)重，患病人數(shù)在1.2億左右，因而深入研究肝細(xì)胞損傷與再生的分子生物學(xué)機(jī)制，開發(fā)治療肝損傷的藥物，具有十分重要的社會(huì)意義。 有關(guān)肝再生調(diào)控的研究已有70多年的歷史，1931年Higgins等首先全面描述了大鼠部分肝切除后的再生過程，1975年Le Brecque等首次證實(shí)在哺乳期的肝臟或肝部分切除的肝臟中，存在一種特異性刺激肝細(xì)胞DNA合成的物質(zhì)，命名為HSS。近30年來，國內(nèi)外學(xué)者圍繞肝再生的機(jī)制，，對(duì)動(dòng)物源及人源的HSS作了大量深入的研究。我們實(shí)驗(yàn)室從上世紀(jì)80年代開始致力于肝刺激物的分離純化研究，獲得了一種對(duì)CCl_4引起的肝損傷具治療作用的組分，命名為人肝細(xì)胞生成素(hepatopoietin，HPO)，并于1995年獲得美國專利。最近，本室崔春萍博士等從新生小牛肝臟中分離得到了三個(gè)具有體外促進(jìn)肝癌細(xì)胞增殖的蛋白質(zhì)，Q-TOF質(zhì)譜測序鑒定出其中之一是一個(gè)富亮氨酸的酸性核蛋白(Leucine-rich acidic nuclear protein，LANP)，其同源的人源體是pp32。pp32是一個(gè)多功能的酸性核蛋白，在正常組織可自我更新的細(xì)胞和腫瘤組織中都有較高水平的表達(dá)。研究發(fā)現(xiàn)其在細(xì)胞的信號(hào)轉(zhuǎn)導(dǎo)、轉(zhuǎn)錄調(diào)控、細(xì)胞骨架動(dòng)力學(xué)以及形態(tài)發(fā)生等過程中都參與作用，但體外促進(jìn)肝細(xì)胞增殖方面目前沒有報(bào)道。 本研究為進(jìn)一步驗(yàn)證該蛋白的促增殖活性并對(duì)其作用機(jī)理作更加深入的研究，需要在體外獲得大量高純度的活性蛋白。首先我們分別從人胎肝cDNA文庫和HL-60細(xì)胞中擴(kuò)增該基因，測序結(jié)果顯示由HL-60細(xì)胞獲得的基因與文獻(xiàn)報(bào)道的pp32完全一致，從cDNA文庫中調(diào)取的核苷酸序列與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.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R346;R575

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 張棟棟;HPPCn相互作用的膜蛋白篩選[D];中國人民解放軍軍事醫(yī)學(xué)科學(xué)院;2010年

本文編號(hào)：1515772