Hif1α基因的进化学分析与高原高血压的相关关系

发布时间：2018-06-16 00:54

  本文选题：高原高血压 + HIF1α基因　； 参考：《青海师范大学》2016年硕士论文

【摘要】：高血压是一种发病机制复杂,发病率高的疾病,是目前最常见的心脑血管疾病之一。在青藏高原之类的高海拔地区,有着气压大,氧浓度低的特点,加上高原地区人群的饮食习惯偏向于高盐高脂,因此在高海拔地区的人群高血压发病几率较平原地区更高,治疗效果也不如平原地区好。低氧环境中,机体内的低氧反应会更容易被激活,HIF1α基因是与低氧反应相关的重要基因之一,HIF1α基因在正常的氧气浓度中不表达,在低氧环境中将激活其表达,从而影响其靶基因的表达含量。在低氧环境下HIF1α基因的表达量显著提升,导致其他与调节血液浓度和血管内皮等相关的基因表达异常,有可能促发高血压的发病。而在长期生存在高原地区的人群和物种,由于长期生活在缺氧环境中,需要适应这种高原的环境,自然选择的进化归根结底是基因的进化,在氨基酸水平的进化主要有三种,一种是正向选择进化,正向选择说明该氨基酸位点受到了环境的影响,产生的进化是对本身有利的,从而进化得以持续;一种是净化选择,许多基因的突变并非有利,因此在自然选择中,会逐渐将有害的功能位点替换掉,称为净化选择;另一种是中性选择,大多数氨基酸都处于一种稳定的状态中,个别核苷酸位点的突变并不改变氨基酸的功能,越是功能比较重要的位点,越倾向于中性选择。由于HIF1α基因与低氧反应关系密切,因此本文中,主要针对HIF1α基因进行分子进化学分析,利用牦牛和藏羚羊等世代居住在高海拔低氧环境的物种的基因序列,研究低氧环境中的物种基因发生的进化特征,进而了解HIF1α基因在氨基酸水平上的选择压力。其中在藏羚羊和牦牛的HIF1α基因中,相对平原地区的家牛和山羊都有一定程度的正向选择,对这些正向选择的位点在蛋白质上分析研究可知,其中的一些位点在蛋白质中承担着重要的功能作用,主要与低氧反应相关。通过HIF1α基因的表达和相关的调控靶基因的功能的了解,可以得知HIF1α调控的靶基因与高血压发病机制相关,而且HIF1α基因的表达量提高有可能提升细胞的氧化应激反应,氧化应激反应与高血压的发病也有强烈的正相关。通过对HIF1α基因的分子进化学分析,了解HIF1α基因与高原地区高血压疾病的相关关系,从而了解到高原地区高血压疾病的特异性,以实现有针对性的精准化医疗。
[Abstract]:Hypertension is one of the most common cardiovascular and cerebrovascular diseases. In high altitude areas such as the Qinghai-Tibet Plateau, they have the characteristics of high pressure and low oxygen concentration, and the diet habits of the people in the plateau tend to be high in salt and fat, so the incidence of hypertension among people in high altitude areas is higher than that in plain areas. The therapeutic effect is not as good as in plain area. HIF1 伪 gene is one of the important genes related to hypoxic reaction, which is not expressed in normal oxygen concentration, but activated in hypoxic environment. Thus, the expression of target gene was affected. The expression of HIF1 伪 gene increased significantly in hypoxic environment, leading to abnormal expression of other genes related to regulating blood concentration and vascular endothelium, which may promote the pathogenesis of hypertension. However, people and species living on the plateau for a long time need to adapt to the environment of plateau because they live in anoxic environment for a long time. The evolution of natural selection is, in the final analysis, the evolution of genes, and there are mainly three kinds of evolution at the level of amino acids. One is forward selection evolution, which indicates that the amino acid site is affected by the environment, and the resulting evolution is beneficial to itself and thus continues; the other is purification selection, where mutations in many genes are not beneficial. Therefore, in natural selection, harmful functional sites are gradually replaced, called purification selection, and the other is neutral selection, in which most amino acids are in a stable state. The mutation of individual nucleotide sites did not change the function of amino acids. Because of the close relationship between HIF1 伪 gene and hypoxic reaction, the molecular chemical analysis of HIF1 伪 gene was carried out in this paper, and the gene sequences of species living in high altitude and low oxygen environment in generations such as yak and Tibetan antelope were used. To study the evolutionary characteristics of species genes in hypoxic environment, and to understand the selection pressure of HIF1 伪 gene at amino acid level. In the HIF1 伪 gene of Tibetan antelope and yak, both cattle and goats in plain area have positive selection to some extent. Some of these sites play an important role in proteins, mainly related to hypoxic reactions. Through the expression of HIF1 伪 gene and the understanding of the function of HIF1 伪 regulating target gene, we can know that the target gene regulated by HIF1 伪 is related to the pathogenesis of hypertension, and the increase of HIF1 伪 gene expression may enhance the oxidative stress response of cells. There is also a strong positive correlation between oxidative stress and hypertension. Through the molecular chemical analysis of HIF1 伪 gene, the relationship between HIF1 伪 gene and hypertension in plateau area was studied, and the specificity of HIF1 伪 gene was found out.
【学位授予单位】：青海师范大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R544.11
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本文编号：2024460