本文關(guān)鍵詞：納米載體介導(dǎo)的hTERT反義寡核苷酸對A549細胞抑制作用研究　出處：《鄭州大學(xué)》2005年碩士論文　論文類型：學(xué)位論文

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【摘要】：端粒(telomere)是位于真核細胞線性染色體末端的天然結(jié)構(gòu),對于保護染色體、防止染色體融合、降解是非常重要的。隨著正常細胞的分裂,端粒的長度逐漸縮短,最終導(dǎo)致細胞的衰老、死亡。在絕大多數(shù)真核細胞中,通過一種特殊的酶即端粒酶(telomerase)來合成端粒DNA重復(fù)序列。端粒酶是一種核蛋白,它利用其自身RNA組分為模板,通過在染色體末端增加(TTAGGG)n重復(fù)序列來補償端粒的縮短。大多數(shù)腫瘤細胞能通過表達端粒酶活性而維持其端粒長度,端粒酶的表達在細胞永生化及癌變過程中起重要作用。研究表明,在80%～85%肺癌組織中檢測到端粒酶陽性,而在癌旁正常組織幾乎均為陰性,表明端粒酶的激活在肺癌的發(fā)生發(fā)展中起重要作用。端粒酶逆轉(zhuǎn)錄酶(human telomerase reverse transcriptase,hTERT)是端粒酶的催化亞單位,是端粒酶活性的限速決定因素。近年來許多研究表明,hTERT的表達與端粒酶活性相一致,因此,hTERT mRNA成為端粒酶活性抑制的理想靶點。 利用反義核酸技術(shù),人工合成靶向hTERT的反義寡核苷酸(Antisense oligodeoxynucleotides,ASODN),抑制hTERT mRNA表達和端粒酶活性,誘導(dǎo)腫瘤細胞凋亡,是目前進行腫瘤基因治療的方向之一。為了克服反義核酸易被核酸酶降解的缺點,常常采用硫代修飾反義核酸的方法,但硫代修飾價格昂貴,難以在臨床應(yīng)用。隨著納米技術(shù)的發(fā)展,利用納米粒作為載體,能夠很好地解決反義核酸被核酸酶降解的問題,并可改善細胞吞噬,提高反義核酸在細胞內(nèi)的穩(wěn)定性,
[Abstract]:Telomere length (telomere) is a natural structure located at the ends of eukaryotic chromosomes, to protect chromosome, prevent chromosome fusion, the degradation is very important. With the normal cell division, telomere length is shortened gradually, eventually leading to cell senescence, death. In most eukaryotic cells, through a special enzyme telomerase (telomerase) synthesis of telomeric DNA repeats. Telomerase is a ribonucleoprotein, it uses its RNA component as a template, by adding on the ends of chromosomes (TTAGGG) n repeat sequence to compensate for telomere shortening. Most of the tumor cells can maintain telomere length through the expression of telomerase activity, telomerase expression an important role in cell immortalization and carcinogenesis. The results show that in the 80% to 85% lung cancer detected in telomerase positive, while in the adjacent normal tissues were almost negative, that end The activation of telomerase plays an important role in the development of lung cancer. Telomerase reverse transcriptase (human telomerase reverse transcriptase, hTERT) is the catalytic subunit of telomerase, telomerase activity is the rate limiting determinant. Many studies show that in recent years, consistent expression and telomerase activity of hTERT so hTERT mRNA an ideal target some inhibition of telomerase activity.
The use of antisense technology, synthetic antisense oligonucleotide targeting hTERT (Antisense, oligodeoxynucleotides, ASODN, mRNA) inhibited the expression of hTERT and telomerase activity and induce apoptosis of tumor cell, is one of the directions of tumor gene therapy. In order to overcome the antisense nucleic acid susceptible to nuclease degradation shortcomings, often using antisense nucleic acid method phosphorothioate, but phosphorothioate is expensive, difficult in clinical application. With the development of nanotechnology, the use of nanoparticles as carrier, can be solved by antisense nucleic acid nuclease degradation problems, and can improve the phagocytic cells, improve the stability of antisense RNA in cells,

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2005
【分類號】：R346;R734.2

【參考文獻】

相關(guān)期刊論文 前6條

1 杜輝,辛?xí)匝?王健;hTERT基因反義核酸對8910卵巢癌細胞端粒酶活性的影響[J];第四軍醫(yī)大學(xué)學(xué)報;2000年03期

2 孫雪光,曹恩華;三鏈核酸穩(wěn)定性和生物學(xué)功能的研究進展[J];生物化學(xué)與生物物理進展;1998年04期

3 張莉萍,曹前;端粒酶RNA反義寡核苷酸對白血病細胞K562增殖的影響[J];中國腫瘤臨床;2002年09期

4 閻慶國,黃高f,張曉暉,王哲;HL-60細胞早期凋亡中端粒酶hTERT基因表達的變化[J];中華血液學(xué)雜志;2000年06期

5 屈藝,劉菽秋,張朝良,白紹槐,歐陽雪松,劉柏林;端粒酶核酶抑制裸鼠移植瘤生長的實驗研究[J];中華醫(yī)學(xué)遺傳學(xué)雜志;1999年06期

6 屈藝,歐陽雪松,劉菽秋,彭曉東,劉柏林;核酶抑制端粒酶活性的實驗研究[J];中華醫(yī)學(xué)遺傳學(xué)雜志;1999年03期

，

本文編號：1383494