本文關(guān)鍵詞： SARS-CoV N蛋白 AHSG 糖脂代謝　出處：《安徽大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：SARS即嚴(yán)重急性呼吸綜合征(severe acute respiratory syndrome, SARS)第一例于2002年12月16日發(fā)生在中國廣東,之后很快在內(nèi)地和香港傳播,最終在全世界蔓延。SARS是一種由新型冠狀病毒——SARS冠狀病毒(severe acute respiratory syndrome coronavirus, SARS-CoV)引起的、以呼吸系統(tǒng)病變?yōu)橹鞯募毙院粑纻魅静�。SARS病人感染病毒后出現(xiàn)發(fā)燒、肌痛及其他的全身性癥狀,會出現(xiàn)血糖血脂明顯升高、致使患有糖尿病病史的病人病情加重,死亡率升高。雖然從2004年之后未發(fā)生人與人之間的SARS傳染,但是并不能完全排除SARS再次爆發(fā)的可能,因為有研究發(fā)現(xiàn),在蝙蝠和麝貓等動物中持續(xù)發(fā)現(xiàn)相似的病毒。近年來,國內(nèi)外對SARS的流行規(guī)律、病理特征、治療措施以及防治藥物和疫苗等方面做了大量的研究,取得了一系列的研究進(jìn)展,但是關(guān)于SARS的致病機(jī)理仍有許多未知的領(lǐng)域,仍需繼續(xù)探索和研究。 SARS-CoV N蛋白是SARS-CoV的第二大結(jié)構(gòu)蛋白,與病毒RNA結(jié)合形成核衣殼。SARS-CoV N蛋白是由422個氨基酸殘基組成,生物物理研究表明SARS-CoV N蛋白由2個獨立的結(jié)構(gòu)域及一個連接區(qū)域構(gòu)成。SARS-CoV N蛋白處于病毒顆粒的核心部分,是核衣殼結(jié)構(gòu)的主要組分,其與基因組RNA結(jié)合形成復(fù)合體,這對于病毒基因組RNA序列的識別、病毒顆粒的組裝有重要作用。SARS-CoV N蛋白又是主要的免疫反應(yīng)原,能誘導(dǎo)強(qiáng)烈的體液免疫和細(xì)胞免疫。在病毒感染早期,SARS-CoV N蛋白能刺激機(jī)體產(chǎn)生抗體,可以從急性早期康復(fù)病人的血清中得到確認(rèn),因此有可能在較早期就能檢測到病毒感染,這對于SARS的早期診斷和預(yù)防具有重要作用。 胎球蛋白A全稱為a2-Heremans-Schmid glycoprotein,縮寫為AHSG。AHSG蛋白是一種由肝臟合成的重要的血漿蛋白,通過血液循環(huán)送達(dá)全身,隨后聚集于礦化的骨骼和牙齒中,參與機(jī)體的生物反應(yīng)。AHSG也是一種天然的對抗胰島素刺激產(chǎn)生的胰島素受體酪氨酸激酶(IRTK)的抑制因子,能特異地抑制體內(nèi)或者體外胰島素刺激引起的胰島素受體(IR)的自身磷酸化,還能抑制外源性底物酪氨酸的磷酸化,最終會阻斷胰島素信號通路的傳導(dǎo)。其次AHSG對于維持體液中鈣離子的濃度及抑制組織細(xì)胞鈣化有重要作用。 本實驗室前期的研究表明,SARS-CoV N蛋白與AHSG存在直接的相互作用,并且通過AHSG介導(dǎo)抑制胰島素信號通路,進(jìn)而影響機(jī)體的糖脂代謝。為了進(jìn)一步驗證SARS-CoV N蛋白對機(jī)體糖脂代謝的影響是通過AHSG介導(dǎo)的,本研究以AHSG基因敲除的C57小鼠和C57野生型小鼠為研究對象,研究SARS-CoV N蛋白對小鼠的糖脂代謝、對葡萄糖的利用和清除能力以及對胰島素的敏感性的影響。同時從細(xì)胞水平和小鼠水平上探討SARS-CoV N蛋白對脂類合成相關(guān)基因FAS,SREBP-1等表達(dá)水平的影響。
[Abstract]:The first case of SARS, severe acute respiratory syndrome (SARS), occurred in Guangdong, China, on December 16th 2002 and spread quickly in the mainland and Hong Kong. SARS eventually spread all over the world. SARS was caused by a new type of coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). SARS patients developed fever, myalgia and other systemic symptoms after infection with the virus. There is a marked increase in blood sugar and blood lipids, leading to an increase in the condition and mortality of patients with a history of diabetes. Although there has been no SARS infection between people since 2004, the possibility of another SARS outbreak cannot be ruled out completely. Because some studies have found that similar viruses have been continuously found in bats and musk cats. In recent years, a great deal of research has been done at home and abroad on the epidemic rule, pathological characteristics, therapeutic measures, drugs and vaccines of SARS. A series of research progress has been made, but there are still many unknown fields about the pathogenesis of SARS, which need to be further explored and studied. SARS-CoV N protein is the second largest structural protein of SARS-CoV. It binds to virus RNA to form nucleocapsid. SARS-CoV N protein is composed of 422 amino acid residues. Biophysical studies show that the SARS-CoV N protein is composed of two independent domains and one connecting region. SARS-CoV N protein is the core of the virus particles and is the main component of the nucleocapsid structure, which binds to the genomic RNA to form a complex. The assembly of viral particles plays an important role in the recognition of viral genomic RNA sequences. SARS-CoV N protein is also the main immunoreactive agent. Can induce strong humoral and cellular immunity. The SARS-CoV N protein stimulates the body to produce antibodies at the early stage of viral infection, which can be confirmed in the sera of patients with acute early recovery, so it is possible to detect viral infections at an earlier stage. This plays an important role in the early diagnosis and prevention of SARS. Fetal globin A is known as a2-Heremans-Schmid glycoprotein, or AHSG.AHSG protein, an important plasma protein synthesized by the liver that passes through the blood circulation and then aggregates in mineralized bones and teeth. AHSG is also a natural inhibitor of insulin receptor tyrosine kinase IRTK, which specifically inhibits the autophosphorylation of insulin receptor IRR induced by insulin stimulation in vivo or in vitro. It can also inhibit tyrosine phosphorylation of exogenous substrates and eventually block the insulin signaling pathway. Secondly, AHSG plays an important role in maintaining calcium concentration in body fluid and inhibiting calcification of tissue cells. Previous studies in our laboratory have shown that SARS-CoV N protein interacts directly with AHSG and inhibits insulin signaling pathway mediated by AHSG. In order to further verify that the effect of SARS-CoV N protein on glycolipid metabolism was mediated by AHSG, C57 mice with AHSG gene knockout and C57 wild-type mice were studied. To study the effect of SARS-CoV N protein on glucose and lipid metabolism in mice, The effects of SARS-CoV N protein on the expression of FASSS-SREBP-1, a gene related to lipid synthesis, were investigated at the cellular and mouse levels.
【學(xué)位授予單位】：安徽大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R511.9

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相關(guān)期刊論文 前3條

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本文編號：1549630