本文選題：高原高血壓 + HIF1α基因��； 參考：《青海師范大學》2016年碩士論文

【摘要】：高血壓是一種發(fā)病機制復雜,發(fā)病率高的疾病,是目前最常見的心腦血管疾病之一。在青藏高原之類的高海拔地區(qū),有著氣壓大,氧濃度低的特點,加上高原地區(qū)人群的飲食習慣偏向于高鹽高脂,因此在高海拔地區(qū)的人群高血壓發(fā)病幾率較平原地區(qū)更高,治療效果也不如平原地區(qū)好。低氧環(huán)境中,機體內(nèi)的低氧反應會更容易被激活,HIF1α基因是與低氧反應相關的重要基因之一,HIF1α基因在正常的氧氣濃度中不表達,在低氧環(huán)境中將激活其表達,從而影響其靶基因的表達含量。在低氧環(huán)境下HIF1α基因的表達量顯著提升,導致其他與調(diào)節(jié)血液濃度和血管內(nèi)皮等相關的基因表達異常,有可能促發(fā)高血壓的發(fā)病。而在長期生存在高原地區(qū)的人群和物種,由于長期生活在缺氧環(huán)境中,需要適應這種高原的環(huán)境,自然選擇的進化歸根結(jié)底是基因的進化,在氨基酸水平的進化主要有三種,一種是正向選擇進化,正向選擇說明該氨基酸位點受到了環(huán)境的影響,產(chǎn)生的進化是對本身有利的,從而進化得以持續(xù);一種是凈化選擇,許多基因的突變并非有利,因此在自然選擇中,會逐漸將有害的功能位點替換掉,稱為凈化選擇;另一種是中性選擇,大多數(shù)氨基酸都處于一種穩(wěn)定的狀態(tài)中,個別核苷酸位點的突變并不改變氨基酸的功能,越是功能比較重要的位點,越傾向于中性選擇。由于HIF1α基因與低氧反應關系密切,因此本文中,主要針對HIF1α基因進行分子進化學分析,利用牦牛和藏羚羊等世代居住在高海拔低氧環(huán)境的物種的基因序列,研究低氧環(huán)境中的物種基因發(fā)生的進化特征,進而了解HIF1α基因在氨基酸水平上的選擇壓力。其中在藏羚羊和牦牛的HIF1α基因中,相對平原地區(qū)的家牛和山羊都有一定程度的正向選擇,對這些正向選擇的位點在蛋白質(zhì)上分析研究可知,其中的一些位點在蛋白質(zhì)中承擔著重要的功能作用,主要與低氧反應相關。通過HIF1α基因的表達和相關的調(diào)控靶基因的功能的了解,可以得知HIF1α調(diào)控的靶基因與高血壓發(fā)病機制相關,而且HIF1α基因的表達量提高有可能提升細胞的氧化應激反應,氧化應激反應與高血壓的發(fā)病也有強烈的正相關。通過對HIF1α基因的分子進化學分析,了解HIF1α基因與高原地區(qū)高血壓疾病的相關關系,從而了解到高原地區(qū)高血壓疾病的特異性,以實現(xiàn)有針對性的精準化醫(yī)療。
[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 偽 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 偽 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 偽 gene and hypoxic reaction, the molecular chemical analysis of HIF1 偽 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 偽 gene at amino acid level. In the HIF1 偽 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 偽 gene and the understanding of the function of HIF1 偽 regulating target gene, we can know that the target gene regulated by HIF1 偽 is related to the pathogenesis of hypertension, and the increase of HIF1 偽 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 偽 gene, the relationship between HIF1 偽 gene and hypertension in plateau area was studied, and the specificity of HIF1 偽 gene was found out.
【學位授予單位】：青海師范大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R544.11
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本文編號：2024460