SARS-CoV N蛋白通过AHSG介导对小鼠糖脂代谢的影响

发布时间：2018-03-01 00:26

本文关键词： SARS-CoV N蛋白 AHSG 糖脂代谢　出处：《安徽大学》2012年硕士论文　论文类型：学位论文

【摘要】：SARS即严重急性呼吸综合征(severe acute respiratory syndrome, SARS)第一例于2002年12月16日发生在中国广东,之后很快在内地和香港传播,最终在全世界蔓延。SARS是一种由新型冠状病毒——SARS冠状病毒(severe acute respiratory syndrome coronavirus, SARS-CoV)引起的、以呼吸系统病变为主的急性呼吸道传染病。SARS病人感染病毒后出现发烧、肌痛及其他的全身性症状,会出现血糖血脂明显升高、致使患有糖尿病病史的病人病情加重,死亡率升高。虽然从2004年之后未发生人与人之间的SARS传染,但是并不能完全排除SARS再次爆发的可能,因为有研究发现,在蝙蝠和麝猫等动物中持续发现相似的病毒。近年来,国内外对SARS的流行规律、病理特征、治疗措施以及防治药物和疫苗等方面做了大量的研究,取得了一系列的研究进展,但是关于SARS的致病机理仍有许多未知的领域,仍需继续探索和研究。 SARS-CoV N蛋白是SARS-CoV的第二大结构蛋白,与病毒RNA结合形成核衣壳。SARS-CoV N蛋白是由422个氨基酸残基组成,生物物理研究表明SARS-CoV N蛋白由2个独立的结构域及一个连接区域构成。SARS-CoV N蛋白处于病毒颗粒的核心部分,是核衣壳结构的主要组分,其与基因组RNA结合形成复合体,这对于病毒基因组RNA序列的识别、病毒颗粒的组装有重要作用。SARS-CoV N蛋白又是主要的免疫反应原,能诱导强烈的体液免疫和细胞免疫。在病毒感染早期,SARS-CoV N蛋白能刺激机体产生抗体,可以从急性早期康复病人的血清中得到确认,因此有可能在较早期就能检测到病毒感染,这对于SARS的早期诊断和预防具有重要作用。胎球蛋白A全称为a2-Heremans-Schmid glycoprotein,缩写为AHSG。AHSG蛋白是一种由肝脏合成的重要的血浆蛋白,通过血液循环送达全身,随后聚集于矿化的骨骼和牙齿中,参与机体的生物反应。AHSG也是一种天然的对抗胰岛素刺激产生的胰岛素受体酪氨酸激酶(IRTK)的抑制因子,能特异地抑制体内或者体外胰岛素刺激引起的胰岛素受体(IR)的自身磷酸化,还能抑制外源性底物酪氨酸的磷酸化,最终会阻断胰岛素信号通路的传导。其次AHSG对于维持体液中钙离子的浓度及抑制组织细胞钙化有重要作用。本实验室前期的研究表明,SARS-CoV N蛋白与AHSG存在直接的相互作用,并且通过AHSG介导抑制胰岛素信号通路,进而影响机体的糖脂代谢。为了进一步验证SARS-CoV N蛋白对机体糖脂代谢的影响是通过AHSG介导的,本研究以AHSG基因敲除的C57小鼠和C57野生型小鼠为研究对象,研究SARS-CoV N蛋白对小鼠的糖脂代谢、对葡萄糖的利用和清除能力以及对胰岛素的敏感性的影响。同时从细胞水平和小鼠水平上探讨SARS-CoV N蛋白对脂类合成相关基因FAS,SREBP-1等表达水平的影响。
[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.
【学位授予单位】：安徽大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R511.9

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