高原低氧环境下大鼠肾脏低氧诱导因子-1α的表达及意义

发布时间：2018-06-09 03:14

本文选题：低氧诱导因子-1α + 高原低氧　；参考：《青海大学》2011年硕士论文

【摘要】：低氧诱导因子-1(hypoxia inducible factor-1,HIF-1)是在研究低氧诱导的红细胞生成素(EPO)基因表达时被发现的。HIF-1作为基因转录的核调节因子,是低氧适应和病理反应中的一个特异的中介因子。HIF-1是一种异二聚体结合DNA的蛋白质因子,主要由HIF-1α、HIF-1β两个亚基组成。两亚单位均含有bHIF-PAS结构域,HIF-1α仅在缺氧细胞的核中存在,HIF-1β则在正常细胞和缺氧细胞的细胞核和细胞质中均有表达,在小鼠各组织中,HIF-1α的表达以肾、心、胸腺最高,肝、脾、肺、睾丸次之,骨骼肌最低。正常条件下,各组织HIF-1α的表达甚少,而低氧状态时,则表现为时间及低氧程度依赖性升高。它具有影响红细胞生成、血管发生、细胞凋亡和增殖等生理、病理过程,并使机体产生一系列的缺氧适应性反应,是对肾脏具有保护作用的一种细胞因子。国内外均有这方面的研究报道,但主要集中在急、慢性肾损伤,肾缺血缺氧损伤,糖尿病肾病,肾移植等方面,在高原低氧方面的报道则不多。目的:人体急性暴露于低压低氧环境后会产生各种病理生理反应,肾脏又是对缺氧比较敏感的器官之一,基于HIF-1α的特定的生理功能,我们推测在此过程中可能有肾脏HIF-1α表达量的变化。方法:为探讨在急性高原低氧环境下肾脏HIF-1α的表达变化,本研究将50只雄性Wistar大鼠由兰州运至青海大学可可西里高原研究基地(海拔4600m),于1d、3d、7d、14d、21d不同缺氧时间点各10只取材,采用全自动生化分析仪检测大鼠肾功能,免疫组化SP法检测肾脏组织HIF-1α的表达及分布,并与对照组(兰州,海拔1500m)进行比较。结果:大鼠在进入高原后,肌酐呈先上升后下降的趋势,在14d达最高值(32.80±9.01μmol,P0.05),差异具有统计学意义,然后逐渐下降,在21d(23.44±5.93μmol)接近对照组水平(23.44±5.93μmol,P0.05),差异无统计学意义。HIF-1α在初入高原后表达量即开始上升,在3d时表达量达高峰(3.68±0.20,P0.05),差异具有统计学意义,后逐渐下降,21d(0.28±0.20)表达接近于对照组水平(0.21±0.14,P0.05),差异无统计学意义。免疫组织切片显示其表达主要位于肾小管上皮细胞内,镜下观察髓质的表达量多于皮质部分,肾小球几乎不表达。结论:本研究观察了大鼠在生理条件下进入高原后肾功能及肾脏组织的HIF-1α表达情况。HIF-1α在低氧初期就表现出了上升趋势,这是通过低氧应激等反应诱导HIF-1α的高表达,减轻低氧对机体带来的损伤。随着对缺氧的习服,HIF-1α的表达逐渐下降。其变化说明高原低氧可诱导大鼠HIF-1α表达,发挥其对肾脏的保护作用,为高原缺氧所致肾损伤的防治提供了理论依据。
[Abstract]:Hypoxia inducible factor-1 (HIF-1) was identified as the nuclear regulator of gene transcription in the study of hypoxia induced erythropoietin (EPO) gene expression. HIF-1 is a specific mediating factor in hypoxic adaptation and pathological response. HIF-1 is a protein factor of heterodimer binding DNA and is mainly composed of two subunits of HIF-1 伪 and HIF-1 尾. The two subunits contained bHIF-PAS domain HIF-1 伪 only in the nuclei of anoxic cells, while HIF-1 尾 was expressed in the nuclei and cytoplasm of normal and anoxic cells. The expression of HIF-1 伪 in the kidney, heart, thymus, liver, spleen and lung was the highest in mice. The testis were the second, and the skeletal muscles were the lowest. Under normal condition, the expression of HIF-1 伪 in all tissues was very low, while in hypoxic state, the expression of HIF-1 伪 was dependent on time and degree of hypoxia. It has many physiological and pathological processes, such as erythropoiesis, angiogenesis, apoptosis and proliferation, and makes the body produce a series of anoxic adaptive responses. It is a protective cytokine to the kidney. There have been reports of this kind of research at home and abroad, but mainly focused on acute, chronic renal injury, renal ischemia and hypoxia injury, diabetic nephropathy, kidney transplantation, and so on. There are few reports on hypoxia at high altitude. Objective: human body exposed to hypobaric hypoxia may produce various pathophysiological responses, and the kidney is one of the organs sensitive to hypoxia, based on the specific physiological function of HIF-1 伪. We speculated that there might be changes of HIF-1 伪 expression in kidney during this process. Methods: in order to investigate the changes of HIF-1 伪 expression in kidney under acute high altitude hypoxia, In this study, 50 male Wistar rats were transported from Lanzhou to the Hoh Xili Plateau Research Base of Qinghai University at an altitude of 4600mg. Ten Wistar rats were collected from 10 rats at different hypoxia time points at 1 day, 3 days, 7 days, 14 days and 21 days, respectively. The renal function of the rats was measured by automatic biochemical analyzer. Immunohistochemical SP method was used to detect the expression and distribution of HIF-1 伪 in renal tissue, and compared with the control group (Lanzhou, 1500 m above sea level). Results: after entering the plateau, the creatinine increased first and then decreased. On the 14th day, the highest value was 32.80 卤9.01 渭 mol 路mol ~ (-1) P _ (0.05), the difference was statistically significant, and then decreased gradually. At 21d(23.44 卤5.93 渭 mol), it was close to the control group (23.44 卤5.93 渭 mol / P), the difference was not statistically significant. The expression of HIF-1 伪 began to increase after entering the plateau. At the 3rd day, the expression reached the peak level (3.68 卤0.20 P0.05), and the difference was statistically significant, but gradually decreased at 21dago (0.28 卤0.20), which was close to the control level of 0.21 卤0.14, P0.05. the difference was not statistically significant. Immunohistochemical sections showed that the expression was mainly in the epithelial cells of renal tubules, and the expression of medulla was more than that of cortex under microscope. Conclusion: in this study, the expression of HIF-1 伪 in renal function and renal tissue was observed after entering into high altitude under physiological conditions. HIF-1 伪 showed an upward trend at the beginning of hypoxia. HIF-1 伪 expression was induced by hypoxic stress, and the damage caused by hypoxia was alleviated. The expression of HIF-1 伪 decreased with hypoxia acclimatization. The changes indicated that hypoxia at high altitude could induce the expression of HIF-1 伪 in rats, exert its protective effect on kidney and provide a theoretical basis for the prevention and treatment of renal injury induced by hypoxia at high altitude.
【学位授予单位】：青海大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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