本文關(guān)鍵詞：線粒體MEF2D氧化修飾水平變化在PD發(fā)病中的作用　出處：《第四軍醫(yī)大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 帕金森病 線粒體 肌細(xì)胞增強(qiáng)因子 多巴胺能神經(jīng)元 氧化修飾 神經(jīng)元存活

【摘要】：帕金森病(PD)是一種神經(jīng)退行性疾病,其主要臨床特征是嚴(yán)重影響患者的運(yùn)動(dòng)功能。隨著我國逐漸進(jìn)入老齡化時(shí)代,PD越來越受到家庭與社會(huì)的關(guān)注[1,2]。PD的主要病理學(xué)特點(diǎn)是中腦SNc區(qū)DA神經(jīng)元發(fā)生變性和死亡,導(dǎo)致多巴胺的釋放減少,但DA神經(jīng)元變性死亡的具體機(jī)制尚不明確。研究發(fā)現(xiàn),約5%-10%的PD例明確是和遺傳因素相關(guān)的,這部分病例與特定的基因改變有關(guān)[3],而大多數(shù)PD病例是散發(fā)的,其確切的發(fā)病原因還不明確。流行病學(xué)研究已經(jīng)證明特定的環(huán)境因素暴露(如神經(jīng)毒劑)和PD的發(fā)病之間有確定的聯(lián)系[4],表明部分神經(jīng)毒劑會(huì)導(dǎo)致或促進(jìn)PD發(fā)病。現(xiàn)在有一個(gè)被廣泛認(rèn)同的觀點(diǎn)是:遺傳與環(huán)境因素共同作用于細(xì)胞,破壞細(xì)胞穩(wěn)態(tài)并導(dǎo)致了氧化應(yīng)激,繼而造成了DA神經(jīng)元的死亡,這其中一個(gè)關(guān)鍵的靶點(diǎn)是線粒體。越來越多的實(shí)驗(yàn)數(shù)據(jù)表明,家族遺傳性PD中一些基因的突變可能是通過影響線粒體功能而產(chǎn)生致病效果,同樣,一些毒劑也是通過這個(gè)途徑導(dǎo)致PD發(fā)病。但是目前對線粒體功能紊亂、氧化應(yīng)激級聯(lián)反應(yīng)、蛋白聚集和誘發(fā)神經(jīng)元死亡的關(guān)鍵分子及信號通路缺乏進(jìn)一步的了解,妨礙了PD的診斷治療,特別是早期發(fā)現(xiàn)疾病。神經(jīng)影像學(xué)、基因組學(xué)和系統(tǒng)生物學(xué)的方法在反映疾病的發(fā)展和變化上仍存在較多的限制和障礙[5]。在發(fā)病機(jī)制深入研究基礎(chǔ)上,探索一種可靠、敏感的PD生物學(xué)標(biāo)記物成為目前急需解決的關(guān)鍵問題。肌細(xì)胞增強(qiáng)因子2(MEF2)最早在骨骼肌的相關(guān)研究中被發(fā)現(xiàn),后來被證實(shí)在越來越多的方面發(fā)揮自己特有的作用。MEF2D已被證實(shí)與神經(jīng)元存活密切相關(guān)[6,7]。本課題組前期研究發(fā)現(xiàn),轉(zhuǎn)錄因子MEF2D對于DA神經(jīng)元的存活起關(guān)鍵性作用[6],不同的細(xì)胞應(yīng)激能夠通過相應(yīng)的信號通路調(diào)節(jié)MEF2D的功能,對神經(jīng)元的存活產(chǎn)生影響。MEF2D在DA神經(jīng)元線粒體中表達(dá),并參與呼吸鏈復(fù)合體I活性的調(diào)節(jié)[7]。在線粒體中,MEF2D特異性調(diào)節(jié)線粒體NADH脫氫酶6(ND6)基因的轉(zhuǎn)錄表達(dá)。ND6是唯一由線粒體輕鏈編碼的蛋白質(zhì),在呼吸鏈復(fù)合體I組裝過程中發(fā)揮著必不可少的作用;降低線粒體MEF2D表達(dá)水平會(huì)明顯抑制呼吸鏈復(fù)合體I的功能,導(dǎo)致細(xì)胞內(nèi)過氧化物水平升高,誘發(fā)神經(jīng)元死亡[8],而大量表達(dá)線粒體靶向MEF2D時(shí)可以保護(hù)神經(jīng)毒素誘發(fā)的DA神經(jīng)元死亡�，F(xiàn)有研究結(jié)果提示:線粒體MEF2D對與線粒體功能具有重要調(diào)控作用,MEF2D與其氧化修飾水平對于把金森并的發(fā)病過程具有重要影響。本研究采用小鼠MPTP-PD亞急性模型,探索在PD模型中,DA神經(jīng)元線粒體MEF2D表達(dá)水平以及氧化修飾水平的動(dòng)態(tài)變化;研究MEF2D、ND6以及線粒體功能變化與DA神經(jīng)元損傷的關(guān)系;通過與其他轉(zhuǎn)錄因子對比,初步分析線粒體MEF2D及其氧化修飾水平作為PD生物學(xué)標(biāo)記物的可行性。實(shí)驗(yàn)一:MPTP-PD模型中動(dòng)態(tài)檢測線粒體MEF2D水平變化方法(1)建立小鼠MPTP-PD亞急性模型,實(shí)驗(yàn)動(dòng)物隨機(jī)分為4組:Con(對照)組,D1(給藥第1天)組,D3(給藥第3天)組,D5(給藥第5天)組,D1、D3和D5組為實(shí)驗(yàn)組。實(shí)驗(yàn)組小鼠按30mg/kg劑量腹腔注射MPTP,注射時(shí)間為上午9點(diǎn),每天一次,連續(xù)5天,對照組于同時(shí)間注射同等劑量0.9%生理鹽水。(2)在給藥的當(dāng)天下午3點(diǎn)處死D1組小鼠,第3天同時(shí)間點(diǎn)處死D3組小鼠,第5天同時(shí)間點(diǎn)處死Con組和D5組小鼠,分別收取樣本。(3)使用免疫熒光染色法動(dòng)態(tài)檢測小鼠中腦DA神經(jīng)元水平變化情況。(4)分離細(xì)胞質(zhì)、細(xì)胞核以及線粒體,使用免疫印跡法檢測分離純化效果。(5)使用免疫印跡法動(dòng)態(tài)檢測小鼠中腦DA神經(jīng)元細(xì)胞核和線粒體MEF2D水平變化情況。(6)分離小鼠的小腦,皮層,紋狀體,使用免疫印跡法分別檢測各腦區(qū)線粒體MEF2D水平變化情況。結(jié)果(1)免疫熒光結(jié)果顯示,在給藥的第1、3、5天中,與對照組相比,小鼠黑質(zhì)致密部DA神經(jīng)元水平出現(xiàn)不同程度顯著下降,在給藥第5天幾乎消失殆盡,證明小鼠MPTP-PD亞急性模型建立成功。(2)免疫印跡結(jié)果顯示細(xì)胞質(zhì),細(xì)胞核以及線粒體分離效果良好,相互之間沒有混雜或污染,達(dá)到實(shí)驗(yàn)要求。(3)在給藥的1、3、5天中,細(xì)胞核MEF2D水平?jīng)]有出現(xiàn)明顯變化,而同區(qū)域的線粒體MEF2D在給藥的第一天即出現(xiàn)明顯下降(P0.05),并在第3天和第5天出現(xiàn)顯著下降(P0.01)。(4)小鼠小腦,皮層,紋狀體線粒體MEF2D水平在給藥的1、3、5天中沒有出現(xiàn)明顯變化,只有黑質(zhì)區(qū)線粒體MEF2D水平與對照組相比明顯降低(P0.05)。結(jié)論(1)在PD模型中,小鼠黑質(zhì)區(qū)線粒體MEF2D水平變化與同時(shí)間點(diǎn)中腦DA神經(jīng)元損失水平相一致,能夠較好地反映DA神經(jīng)元水平變化情況。(2)小鼠黑質(zhì)區(qū)線粒體MEF2D水平變化并不是由非特異性應(yīng)激反應(yīng)所引起,其變化水平與DA神經(jīng)元受損程度密切相關(guān)。實(shí)驗(yàn)二:MPTP-PD模型中動(dòng)態(tài)觀測核轉(zhuǎn)錄因子Nurr1和線粒體轉(zhuǎn)錄因子TFAM的水平變化方法(1)同實(shí)驗(yàn)一建立小鼠MPTP-PD亞急性模型,隨機(jī)分為4組:Con組,D1組,D3組,D5組。(2)使用免疫印跡法檢測小鼠中腦DA神經(jīng)元Nurr1和TFAM動(dòng)態(tài)水平變化。結(jié)果(1)在PD模型中,小鼠中腦多巴胺能神經(jīng)元細(xì)胞核轉(zhuǎn)錄因子Nurr1在給藥的第1、3、5天中沒有出現(xiàn)明顯的變化,同區(qū)域線粒體轉(zhuǎn)錄因子TFAM在給藥的第1天和第3天沒有明顯變化,第5天時(shí)出現(xiàn)明顯下降(P0.05)。結(jié)論(1)在PD模型中,細(xì)胞核轉(zhuǎn)錄因子Nurr1和線粒體轉(zhuǎn)錄因子TFAM這兩種重要的存活相關(guān)轉(zhuǎn)錄因子對于多巴胺能神經(jīng)元的水平變化都不夠敏感,線粒體MEF2D相比于Nurr1和TFAM,對于多巴胺能神經(jīng)元的損傷更加敏感,能夠更好地反映多巴胺能神經(jīng)元的受損程度。實(shí)驗(yàn)三:觀察線粒體MEF2D氧化修飾水平與DA神經(jīng)元線粒體功能變化的相關(guān)性方法(1)同實(shí)驗(yàn)一建立小鼠MPTP-PD亞急性模型,隨機(jī)分為4組:Con組,D1組,D3組,D5組。(2)使用Oxy Blot技術(shù)檢測線粒體MEF2D氧化修飾水平動(dòng)態(tài)變化。(3)使用q RT-PCR技術(shù)檢測ND6 m RNA水平的動(dòng)態(tài)變化。(4)通過測定在450nm下NADH的氧化速率檢測呼吸鏈復(fù)合體I活性的動(dòng)態(tài)變化。結(jié)果(1)在PD模型中,與對照組相比,中腦DA神經(jīng)元線粒體MEF2D氧化修飾水平自給藥第3天開始出現(xiàn)明顯升高,在給藥的1、3、5天中呈逐漸升高趨勢。(2)同區(qū)域ND6 m RNA水平在給藥第3天明顯下降(P0.05),在第5天顯著下降(P0.01)。(3)同區(qū)域Complex I活性在第3天和第5天時(shí)出現(xiàn)顯著下降(P0.01)。結(jié)論(1)在PD模型中,小鼠中腦多巴胺能神經(jīng)元線粒體MEF2D氧化修飾水平與對照組相比明顯升高,同時(shí)伴有ND6轉(zhuǎn)錄水平的明顯下降以及呼吸鏈復(fù)合體I活性顯著降低,明確了線粒體MEF2D氧化修飾水平與ND6轉(zhuǎn)錄水平以及線粒體功能變化的一致性。
[Abstract]:Parkinson's disease (PD) is a neurodegenerative disease, the main clinical features are seriously affecting the patient's motor function. As China has gradually entered the aging era, PD has received more and more attention to family and society the main pathological features of [1,2].PD is SNc DA 'midbrain neurons degeneration and death, leading to dopamine the release of reduced, but the specific mechanism of DA neuron degeneration and death is not clear. The study found that PD were about 5%-10% and is clearly related to genetic factors, this part of the cases with specific genes related to changes in [3], and most PD cases are scattered hair, its exact pathogenesis is not clear. Epidemiological studies have demonstrated exposure to specific environmental factors (such as nerve agents) there is a definite link between the incidence of [4] and PD, showed that some nerve agents can cause or promote the pathogenesis of PD. There is now a widely accepted view is:. Transfer and environmental factors contribute to the destruction of cells, cellular homeostasis and leads to oxidative stress, resulting in the death of DA neurons, which is one of the key targets of mitochondrial. More and more experimental data showed that the same mutation of some genes in familial PD may be caused by pathogenic effect, effect of mitochondria the function, some agents also through the pathway leading to the pathogenesis of PD. But the mitochondrial dysfunction, oxidative stress cascade, the lack of a better understanding of the key molecular protein aggregation and induced neuronal death and signaling pathways, interferes with the diagnosis and treatment of PD, especially the early detection of the disease. Neuroimaging, genomics and method systems biology there are still many limitations and obstacles [5]. based on in-depth study of the pathogenesis of the disease in reflecting disease development and change, to explore a reliable, sensitive PD biological markers sense becomes the key problem solved urgently. Myocyte enhancer factor 2 (MEF2) was originally discovered in the study of skeletal muscle, later proved to play a role in their own unique.MEF2D have been linked to neuronal survival of [6,7]. is closely related to our previous study found that in more and more. The transcription factor MEF2D in DA neurons play a key role in [6], different cell stress can regulate MEF2D signaling through the corresponding function, which affect the expression of.MEF2D in DA neurons in mitochondria on neuronal survival, and participate in the respiratory chain complex I regulating the activity of [7]. in mitochondria, MEF2D specific regulation of mitochondrial NADH dehydrogenase 6 (ND6) gene expression by mitochondrial.ND6 is the only light chain encoding protein in respiratory chain complex I assembly process plays an indispensable for Use; mitochondria MEF2D expression can inhibit the function of respiratory chain complex I, resulting in increased superoxide levels in cells, [8] induced neuronal death, and a large number of expression can protect the mitochondrial targeting to MEF2D neurotoxin induced DA neuronal death. Existing research results suggest that MEF2D plays an important regulatory role of mitochondria and mitochondrial function, the level of MEF2D and for the oxidative modification plays an important role in the pathogenesis of Higginson. This study used mice in subacute MPTP-PD model exploration in PD model, the DA Neuron Mitochondrial MEF2D expression level and dynamic change of the level of oxidative modification; on MEF2D, ND6 and the relationship between mitochondrial function and change of DA neurons with other transcription factors; the level of contrast, preliminary analysis of mitochondrial MEF2D and its feasibility as the oxidative modification of PD biomarkers. Experiment one: MP Change method in TP-PD model of dynamic detection of the level of mitochondrial MEF2D (1) mice in subacute MPTP-PD model, the experimental animal were randomly divided into 4 groups: Con (control group), D1 group (administered first days), D3 (administered third days) group, D5 (administered fifth days) group, D1, D3 and the D5 group for the experimental group. The experimental group of mice by intraperitoneal injection of 30mg/kg MPTP, injection time is at 9 in the morning, once a day for 5 consecutive days, the control group at the same time injected with the same dose of saline. 0.9% (2) in the administration of 3 PM the same day were D1 mice, third days time the mice of D3 group were killed, and fifth day time after Con group and D5 group respectively for samples. (3) using immunofluorescence dynamic changes of murine mesencephalic DA neurons detected. (4) the separation of cytoplasm, nucleus and mitochondria, the effect of pure separation using Western blot test. (5) the use of immune Western blot detection of small dynamic The changes of rat DA neurons of midbrain nuclei and mitochondria. The level of MEF2D (6) isolated from mouse cerebellum, cortex, striatum, respectively to detect the changes of the level of mitochondrial MEF2D in various brain regions by Western blotting. Results (1) immunofluorescence results showed that, in the administration of the first 1,3,5 days, compared with the control group, the mice black nigra DA neurons appeared different degree of level decreased significantly in the administration of fifth days almost disappeared, that mice in subacute MPTP-PD model was established successfully. (2) the results of Western blot showed that the cytoplasm, nucleus and mitochondria isolation effect is good, no pollution or mixed with each other, meet the requirement of experiment. (3) in drug delivery 1,3,5 day, nuclear MEF2D levels did not show significant changes, and mitochondrial MEF2D in same region on the first day of administration is decreased significantly (P0.05), and in third days and fifth days was significantly decreased (P0.01) (4). Mouse cerebellar cortex, striatum, mitochondrial MEF2D levels did not show significant changes in the administration of 1,3,5 days, only the level of mitochondrial MEF2D in the substantia nigra decreased significantly compared with the control group (P0.05). Conclusion (1) in the PD model, the changes of mitochondrial MEF2D levels in mouse substantia nigra of midbrain DA neurons and at the same time point loss level consistent, can better reflect the changes of DA level. (2) neurons in substantia nigra of mice mitochondrial MEF2D level changes and not caused by nonspecific stress responses, it is closely related to the changes of neurons and DA damage. Experiment two: change the level of dynamic observation of nuclear transcription factor Nurr1 and mitochondrial transcription factor TFAM method the MPTP-PD model (1) the mice in subacute MPTP-PD model, were randomly divided into 4 groups: Con group, D1 group, D3 group, D5 group. (2) the use of Western blot detection of mouse mesencephalic DA neurons Nurr1 and TFAM The dynamic level changes. Results (1) in the PD model, mouse midbrain dopaminergic neurons nuclear transcription factor Nurr1 did not show significant changes in the administration of the first 1,3,5 days in the same area, mitochondrial transcription factor TFAM in the administration of first days and third days did not change significantly, decreased significantly at day fifth (P0.05) conclusion. (1) in the PD model, the nuclear transcription factor Nurr1 and mitochondrial transcription factor TFAM of the two important transcription factors related to the survival of dopaminergic neurons changes are not sensitive, mitochondrial MEF2D compared to Nurr1 and TFAM, is more sensitive to the damage of dopaminergic neurons can better reflect dopaminergic neurons the extent of the damage. Experiment three: method of correlation between observed changes of mitochondrial oxidative modification of MEF2D and DA neurons of mitochondrial function (1) with the established mouse MPTP-PD model with subacute. The machine is divided into 4 groups: Con group, D1 group, D3 group, D5 group. (2) detection of mitochondrial MEF2D oxidative modification changes using Oxy Blot technology. (3) using the Q RT-PCR technique to detect the dynamic changes of ND6 m RNA. (4) the dynamic determination of oxidation rate of detection of respiratory chain complex NADH under the 450nm I activity. Results (1) in PD model, compared with the control group, DA neurons of midbrain mitochondrial MEF2D oxidative modification level supply drug appeared third days increased significantly, in the administration of 1,3,5 days increased gradually. (2) with ND6 m RNA in the level of regional administration third the day was significantly decreased (P0.05), decreased significantly after fifth days (P0.01). (3) with the regional Complex I activity in third days and fifth days were significantly reduced (P0.01). Conclusion (1) in the PD model, mouse midbrain dopaminergic neurons oxidative modification of mitochondrial MEF2D levels compared with the control group increased significantly. At the same time with ND6 The transcriptional level decreased significantly, and the activity of I in respiratory chain complex decreased significantly. The consistency of mitochondrial MEF2D oxidative modification level with ND6 transcriptional level and mitochondrial function was confirmed.

【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R742.5

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 李玉華,徐倉寶,張亞萍,王亞文,林元喜;硒、維生素E等抑制低密度脂蛋白氧化修飾作用的比較研究[J];西安醫(yī)科大學(xué)學(xué)報(bào);2001年02期

2 張穎;杜丹華;金濤;高鵬;王贊;;線粒體乙醛脫氫酶前體的氧化修飾在帕金森病發(fā)病機(jī)制中的作用[J];中國實(shí)驗(yàn)診斷學(xué);2011年08期

3 丁振華;低密度脂蛋白的氧化修飾及其理化、生物學(xué)性質(zhì)的改變[J];國外醫(yī)學(xué)(生理、病理科學(xué)與臨床分冊);1994年02期

4 李其富,王庸晉,歐陽淑其;氧化修飾脂蛋白與動(dòng)脈粥樣硬化[J];長治醫(yī)學(xué)院學(xué)報(bào);1999年01期

5 李家富,何濤,鄧輝勝,羅興林,魏宗德;槲皮素、異鼠李素對體外低密度脂蛋白氧化修飾的影響[J];心臟雜志;2003年05期

6 鄧祖躍,劉秉文,周靜,張祖輝,劉宇,白懷;脂蛋白的氧化修飾對血凝及纖溶活性的影響[J];中國病理生理雜志;2004年10期

7 陳國珍;飲食脂肪對低密度脂蛋白氧化修飾的影響[J];昆明醫(yī)學(xué)院學(xué)報(bào);1995年03期

8 呂曉華,王瑞淑;鎂對人體低密度脂蛋白氧化修飾的影響[J];營養(yǎng)學(xué)報(bào);2003年04期

9 柏慶利;冠心病患者血清氧化修飾低密度脂蛋白抗體和可溶性細(xì)胞間黏附分子相關(guān)性研究[J];江蘇大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2005年04期

10 丁振華;低密度脂蛋白氧化修飾的研究[J];生理科學(xué)進(jìn)展;1994年01期

相關(guān)會(huì)議論文 前10條

1 張穎;楊藝敏;胡林森;;氧化修飾蛋白質(zhì)在帕金森病發(fā)病機(jī)制中的作用[A];中華醫(yī)學(xué)會(huì)第十三次全國神經(jīng)病學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2010年

2 張穎;楊藝敏;胡林森;;帕金森病細(xì)胞模型中線粒體乙醛脫氫酶前體氧化修飾水平的變化[A];中華醫(yī)學(xué)會(huì)第十三次全國神經(jīng)病學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2010年

3 王偉燕;朱建華;;氧化修飾低密度脂蛋白受體-1與動(dòng)脈粥樣硬化[A];2007年浙江省心電生理與起搏學(xué)術(shù)年會(huì)論文匯編[C];2007年

4 殷俊;張波;劉梁;劉長林;;DNA加速氧化修飾的銅鋅超氧化物歧化酶聚集[A];中國化學(xué)會(huì)第26屆學(xué)術(shù)年會(huì)化學(xué)生物分會(huì)場論文集[C];2008年

5 傅強(qiáng);劉秉文;;抗氧化劑對HDL氧化修飾的影響[A];中國生物化學(xué)與分子生物學(xué)會(huì)第八屆會(huì)員代表大會(huì)暨全國學(xué)術(shù)會(huì)議論文摘要集[C];2001年

6 呂曉華;王瑞淑;;鎂對人體低密度脂蛋白氧化修飾的影響[A];四川省營養(yǎng)學(xué)會(huì)2003年學(xué)術(shù)會(huì)議專題報(bào)告及論文摘要匯編[C];2003年

7 傅強(qiáng);劉秉文;;次氯酸與Cu~(2+)氧化修飾高密度脂蛋白[A];中國生物化學(xué)與分子生物學(xué)會(huì)第八屆會(huì)員代表大會(huì)暨全國學(xué)術(shù)會(huì)議論文摘要集[C];2001年

8 左勇;楊潔;項(xiàng)秉鋼;孫序序;倉輝;王毓美;易靜;;氧化修飾Caspase-9介導(dǎo)其剪切和激活——氧化應(yīng)激誘導(dǎo)凋亡的新機(jī)制[A];中國細(xì)胞生物學(xué)學(xué)會(huì)第九次會(huì)員代表大會(huì)暨青年學(xué)術(shù)大會(huì)論文摘要集[C];2007年

9 盧景芬;程驛;古力努爾;王夔;;稀土離子對LDL氧化修飾的影響[A];第五屆全國自由基生物學(xué)與自由基醫(yī)學(xué)學(xué)術(shù)討論會(huì)論文摘要匯編[C];2000年

10 王明霞;陳琳;邊紅烈;邸曉光;魏文青;;膽紅素抑制低密度脂蛋白的氧化修飾[A];中國營養(yǎng)學(xué)會(huì)第八次全國營養(yǎng)學(xué)術(shù)會(huì)議論文摘要匯編[C];2000年

相關(guān)博士學(xué)位論文 前4條

1 胡德輝;L-型鈣通道在蛋白質(zhì)非酶性糖化氧化修飾損傷神經(jīng)元中的作用[D];第一軍醫(yī)大學(xué);2005年

2 張穎;PSI誘導(dǎo)的PC12細(xì)胞PD模型的氧化修飾亞蛋白質(zhì)組學(xué)研究[D];吉林大學(xué);2007年

3 魏鈞;過氧化氫誘導(dǎo)的ECFC細(xì)胞氧化應(yīng)激模型的氧化修飾亞蛋白質(zhì)組學(xué)研究[D];吉林大學(xué);2012年

4 高立;神經(jīng)生長因子MEF2D氧化修飾及降解在帕金森發(fā)病機(jī)制中的作用[D];第四軍醫(yī)大學(xué);2013年

相關(guān)碩士學(xué)位論文 前7條

1 高飛;線粒體MEF2D氧化修飾水平變化在PD發(fā)病中的作用[D];第四軍醫(yī)大學(xué);2015年

2 袁曉亮;氧化修飾與抗氧化劑在動(dòng)脈粥樣硬化形成中作用機(jī)制的實(shí)驗(yàn)研究[D];第四軍醫(yī)大學(xué);2003年

3 周立堯;氧化修飾對高密度脂蛋白功能的影響及與ABCA1的關(guān)系[D];南方醫(yī)科大學(xué);2007年

4 李宏;天然及氧化修飾高密度脂蛋白對內(nèi)皮細(xì)胞部分分泌功能的影響[D];四川大學(xué);2005年

5 鄧祖躍;氧化修飾脂蛋白對血凝、纖溶及血小板聚集功能的影響[D];四川大學(xué);2003年

6 卜梓斌;HDL及其亞型氧化修飾對ECV304細(xì)胞組織因子表達(dá)的影響及相關(guān)機(jī)制[D];南華大學(xué);2008年

7 孟芳;五種黃酮類化合物抑制LDL及HDL氧化修飾作用的研究[D];四川大學(xué);2004年

，

本文編號：1359606