本文選題：低氧誘導(dǎo)因子-1α + 高原低氧　； 參考：《青海大學(xué)》2011年碩士論文

【摘要】：低氧誘導(dǎo)因子-1(hypoxia inducible factor-1,HIF-1)是在研究低氧誘導(dǎo)的紅細(xì)胞生成素(EPO)基因表達(dá)時被發(fā)現(xiàn)的。HIF-1作為基因轉(zhuǎn)錄的核調(diào)節(jié)因子,是低氧適應(yīng)和病理反應(yīng)中的一個特異的中介因子。HIF-1是一種異二聚體結(jié)合DNA的蛋白質(zhì)因子,主要由HIF-1α、HIF-1β兩個亞基組成。兩亞單位均含有bHIF-PAS結(jié)構(gòu)域,HIF-1α僅在缺氧細(xì)胞的核中存在,HIF-1β則在正常細(xì)胞和缺氧細(xì)胞的細(xì)胞核和細(xì)胞質(zhì)中均有表達(dá),在小鼠各組織中,HIF-1α的表達(dá)以腎、心、胸腺最高,肝、脾、肺、睪丸次之,骨骼肌最低。正常條件下,各組織HIF-1α的表達(dá)甚少,而低氧狀態(tài)時,則表現(xiàn)為時間及低氧程度依賴性升高。它具有影響紅細(xì)胞生成、血管發(fā)生、細(xì)胞凋亡和增殖等生理、病理過程,并使機(jī)體產(chǎn)生一系列的缺氧適應(yīng)性反應(yīng),是對腎臟具有保護(hù)作用的一種細(xì)胞因子。國內(nèi)外均有這方面的研究報道,但主要集中在急、慢性腎損傷,腎缺血缺氧損傷,糖尿病腎病,腎移植等方面,在高原低氧方面的報道則不多。 目的:人體急性暴露于低壓低氧環(huán)境后會產(chǎn)生各種病理生理反應(yīng),腎臟又是對缺氧比較敏感的器官之一,基于HIF-1α的特定的生理功能,我們推測在此過程中可能有腎臟HIF-1α表達(dá)量的變化。 方法:為探討在急性高原低氧環(huán)境下腎臟HIF-1α的表達(dá)變化,本研究將50只雄性Wistar大鼠由蘭州運至青海大學(xué)可可西里高原研究基地(海拔4600m),于1d、3d、7d、14d、21d不同缺氧時間點各10只取材,采用全自動生化分析儀檢測大鼠腎功能,免疫組化SP法檢測腎臟組織HIF-1α的表達(dá)及分布,并與對照組(蘭州,海拔1500m)進(jìn)行比較。 結(jié)果:大鼠在進(jìn)入高原后,肌酐呈先上升后下降的趨勢,在14d達(dá)最高值(32.80±9.01μmol,P0.05),差異具有統(tǒng)計學(xué)意義,然后逐漸下降,在21d(23.44±5.93μmol)接近對照組水平(23.44±5.93μmol,P0.05),差異無統(tǒng)計學(xué)意義。HIF-1α在初入高原后表達(dá)量即開始上升,在3d時表達(dá)量達(dá)高峰(3.68±0.20,P0.05),差異具有統(tǒng)計學(xué)意義,后逐漸下降,21d(0.28±0.20)表達(dá)接近于對照組水平(0.21±0.14,P0.05),差異無統(tǒng)計學(xué)意義。免疫組織切片顯示其表達(dá)主要位于腎小管上皮細(xì)胞內(nèi),鏡下觀察髓質(zhì)的表達(dá)量多于皮質(zhì)部分,腎小球幾乎不表達(dá)。 結(jié)論:本研究觀察了大鼠在生理條件下進(jìn)入高原后腎功能及腎臟組織的HIF-1α表達(dá)情況。HIF-1α在低氧初期就表現(xiàn)出了上升趨勢,這是通過低氧應(yīng)激等反應(yīng)誘導(dǎo)HIF-1α的高表達(dá),減輕低氧對機(jī)體帶來的損傷。隨著對缺氧的習(xí)服,HIF-1α的表達(dá)逐漸下降。其變化說明高原低氧可誘導(dǎo)大鼠HIF-1α表達(dá),發(fā)揮其對腎臟的保護(hù)作用,為高原缺氧所致腎損傷的防治提供了理論依據(jù)。
[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 偽 and HIF-1 尾. The two subunits contained bHIF-PAS domain HIF-1 偽 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 偽 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 偽 in all tissues was very low, while in hypoxic state, the expression of HIF-1 偽 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 偽. We speculated that there might be changes of HIF-1 偽 expression in kidney during this process. Methods: in order to investigate the changes of HIF-1 偽 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 偽 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 鹵9.01 渭 mol 路mol ~ (-1) P _ (0.05), the difference was statistically significant, and then decreased gradually. At 21d(23.44 鹵5.93 渭 mol), it was close to the control group (23.44 鹵5.93 渭 mol / P), the difference was not statistically significant. The expression of HIF-1 偽 began to increase after entering the plateau. At the 3rd day, the expression reached the peak level (3.68 鹵0.20 P0.05), and the difference was statistically significant, but gradually decreased at 21dago (0.28 鹵0.20), which was close to the control level of 0.21 鹵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 偽 in renal function and renal tissue was observed after entering into high altitude under physiological conditions. HIF-1 偽 showed an upward trend at the beginning of hypoxia. HIF-1 偽 expression was induced by hypoxic stress, and the damage caused by hypoxia was alleviated. The expression of HIF-1 偽 decreased with hypoxia acclimatization. The changes indicated that hypoxia at high altitude could induce the expression of HIF-1 偽 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.
【學(xué)位授予單位】：青海大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R363

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 宋海邦,瓦龍美;低氧誘導(dǎo)因子-1研究進(jìn)展[J];解剖科學(xué)進(jìn)展;2002年04期

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本文編號：1998597