本文選題：秀麗新桿線蟲 + 肌管素�。� 參考：《吉林大學(xué)》2011年博士論文

【摘要】：第一篇:蛋白質(zhì)磷酸酶是細(xì)胞信號轉(zhuǎn)導(dǎo)過程中發(fā)揮至關(guān)重要作用的一類蛋白質(zhì),其家族成員與多種人類疾病的發(fā)生、發(fā)展密切相關(guān)。肌管素磷酸酶亞家族(Myotubularins,MTMs)隸屬于蛋白質(zhì)磷酸酶超家族,該亞家族成員以磷酸肌醇(phosphatidylinositol, PI)作為其特異性的催化底物進(jìn)行去磷酸化。人類的肌管素磷酸酶機(jī)組成員MTM-1突變可導(dǎo)致X-連鎖的肌小管性肌病,MTMR2和MTMR13的突變可導(dǎo)致腓骨肌萎縮癥,但肌管素磷酸酶引發(fā)其相關(guān)疾病的機(jī)理尚不清楚。本研究選用秀麗新桿線蟲作為生物模型,利用RNA干擾的方法及相關(guān)的突變體對線蟲肌管素磷酸酶成員ceMTM3、ceMTM6和ceMTM9進(jìn)行了研究。 我們的研究結(jié)果表明,ceMTM3能夠影響線蟲體內(nèi)肌纖維的保持并對線蟲體內(nèi)自吞噬的發(fā)生起著負(fù)調(diào)控的作用。利用RNA干擾的方法降低線蟲體內(nèi)ceMTM3的表達(dá)量可加速線蟲在衰老的過程中肌纖維的流失,使線蟲的肌肉細(xì)胞發(fā)生萎縮變小,并在線蟲體內(nèi)肌肉細(xì)胞及其他組織中引起自吞噬水平顯著升高。在自吞噬水平升高后,ceMTM3表達(dá)量的降低還導(dǎo)致了細(xì)胞體內(nèi)溶酶體水平升高以及細(xì)胞壞死。Atg-18在線蟲體內(nèi)發(fā)生自吞噬的過程中能夠與PI3P相結(jié)合并對自吞噬小體的形成起重要的調(diào)節(jié)作用,atg-18突變型線蟲自身存在運(yùn)動(dòng)障礙,并且相比野生型線蟲其肌肉細(xì)胞內(nèi)肌纖維排列混亂。當(dāng)對atg-18突變型線蟲進(jìn)行ceMTM3干擾后,我們發(fā)現(xiàn)在atg-18突變型線蟲的體內(nèi)降低ceMTM3的表達(dá)量并未使該突變株線蟲體內(nèi)的肌纖維排列進(jìn)一步惡化。這說明ceMTM3對線蟲肌纖維保持的調(diào)節(jié)作用是通過其對自吞噬的調(diào)控來實(shí)現(xiàn)的。本研究為揭示人類肌纖維保持的調(diào)節(jié)機(jī)制及治療人骨骼肌減少癥提供了依據(jù)和基礎(chǔ)。此外,我們還對線蟲體內(nèi)另外兩名肌管素成員ceMTM6和ceMTM9的生物學(xué)功能進(jìn)行了研究。研究結(jié)果表明,mtm-6突變型線蟲相比野生型體長較短、存在運(yùn)動(dòng)障礙。在發(fā)育的過程中進(jìn)行肌肉染色的結(jié)果表明,相比野生型,mtm-6突變型的線蟲肌細(xì)胞間隙較大且肌細(xì)胞較小,此外,約20% mtm-6突變型線蟲的生殖腺在發(fā)育的過程中延伸方向發(fā)生了錯(cuò)誤。整合素在細(xì)胞表面的分布和表達(dá)對細(xì)胞之間的粘附和細(xì)胞遷移有重要的調(diào)節(jié)作用。我們初步的研究結(jié)果表明,mtm-6能夠影響線蟲體內(nèi)神經(jīng)細(xì)胞DTCs表面整合素INA-1的表達(dá)和分布,而這極有可能是ceMTM6影響線蟲肌肉細(xì)胞和生殖腺發(fā)育的原因之一。ceMTM9不具備催化活性中心,之前的研究結(jié)果表明,ceMTM9可與ceMTM6結(jié)合形成復(fù)合體共同發(fā)揮作用。本研究的結(jié)果表明,mtm-9突變型線蟲可使線蟲發(fā)育遲緩、體長較小、產(chǎn)卵數(shù)明顯降低Bagged Worm比率顯著升高并且壽命縮短。對mtm-9突變型線蟲進(jìn)行ceMTM3干擾的結(jié)果表明,ceMTM9和ceMTM3之間可能存在著相互代償?shù)淖饔谩?第二篇:酒精飲料是人類日常生活中必不可少的飲品。長期酗酒對人體有較大傷害,但近期的研究結(jié)果表明,長期適量飲酒可降低人類某些疾病的發(fā)病率,因此飲酒的利弊仍存在爭議。本研究以秀麗新桿線蟲作為模型,研究了不同濃度的酒精長期刺激線蟲各種生命活動(dòng)的影響。研究結(jié)果表明,長期高濃度的酒精刺激(≥4%)使線蟲壽命縮短、產(chǎn)卵數(shù)減少、運(yùn)動(dòng)能力減弱。有趣的是,長期低濃度的酒精刺激(1-2%)可使線蟲壽命延長。盡管產(chǎn)卵數(shù)有所減少,但長期2%濃度的酒精刺激可使線蟲的壽命延長約2.76天,延長率達(dá)14.53%,并且伴隨著運(yùn)動(dòng)的衰老程度減緩。研究發(fā)現(xiàn),這種作用與線蟲體內(nèi)的類胰島素信號通路以及轉(zhuǎn)錄因子Sir-2.1密切相關(guān)。相比未刺激的對照組,無論從卵、幼蟲還是成蟲開始2%酒精刺激都可使線蟲壽命顯著延長。本研究證明了線蟲是研究長期酒精刺激的優(yōu)秀模型并且長期少量的酒精刺激能夠?qū)C(jī)體產(chǎn)生積極的作用。本研究為進(jìn)一步研究不同劑量酒精長期刺激對人類的生理功能的影響以及所引發(fā)的與之相關(guān)的分子機(jī)制奠定了基礎(chǔ)。
[Abstract]:Protein phosphatase is a kind of protein that plays a vital role in cell signal transduction. Its family members are closely related to the development of a variety of human diseases. The Myotubularins (MTMs) belongs to the protein phosphatase superfamily, and the member of the subfamily is inositol phosphate (phosphatidylino). Sitol, PI) dephosphorylation as its specific catalytic substrate. Human myotin phosphatase unit MTM-1 mutation can lead to X- linked myomatosis. Mutations in MTMR2 and MTMR13 can lead to fibula muscular dystrophy, but the mechanism of myotin phosphatase that causes its related diseases is not clear. As a biological model, the ceMTM3, ceMTM6 and ceMTM9 of the nematode myotube phosphatase were studied by means of RNA interference and related mutants.
Our results showed that ceMTM3 could affect the retention of the muscle fibers in the nematode and negatively regulated the self phagocytosis of the nematode in the nematode. The reduction of the ceMTM3 expression in the nematode by RNA interference could accelerate the loss of muscle fibers in the aging process, and reduce the atrophy of the nematode muscle cells. The level of autophagy increased significantly in the muscle cells and other tissues in the body of the worm. The decrease of the expression of ceMTM3 also resulted in the increase of the lysosome level in the cells and the formation of the autophagy of the autophagocytic body in the process of the autophagy of the cell necrosis.Atg-18 in the body of the cells after the increase of autophagy. Important regulation, atg-18 mutant nematodes themselves have dyskinesia, and the muscle fibers in the muscle cells of the wild type nematode are confused. When ceMTM3 interference is done to atg-18 mutant nematodes, we found that the reduction of ceMTM3 in the body of the atg-18 mutant nematode did not make the muscle fiber in the mutant nematode. This shows that the regulation of ceMTM3 on the retention of nematode muscle fibers is achieved through its regulation of autophagy. This study provides a basis and basis for revealing the regulatory mechanism of human muscle fiber retention and the treatment of human skeletal myocytosis. In addition, we also have two other myosin members, ceMTM6 and C, in line worms. The biological function of eMTM9 was studied. The results showed that the mtm-6 mutated nematode was shorter than the wild type, and there was a dyskinesia. The results of muscle staining during development showed that the myocytes of the nematode of the mtm-6 mutant were larger and smaller than the wild type. In addition, about 20% mtm-6 mutant nematodes were born. The distribution and expression of integrin on cell surface have important regulatory effect on cell adhesion and cell migration. Our preliminary results show that mtm-6 can affect the expression and distribution of DTCs surface integrin INA-1 in the nerve cells of the nematode, and this is very likely. It is one of the reasons that ceMTM6 affects the development of the nematode muscle cells and the reproductive glands of the nematode..ceMTM9 does not have the catalytic activity center. The previous research results show that ceMTM9 can combine with ceMTM6 to form complex complex. The results of this study show that the mtm-9 mutant nematode can make the nematode grow slow, the body length is smaller, and the number of spawns obviously reduces the Bagged W. The ORM ratio was significantly higher and the life span was shortened. The results of ceMTM3 interference to the mtm-9 mutant nematode showed that there might be a mutual compensatory effect between ceMTM9 and ceMTM3.
Second: alcohol is an essential drink in human daily life. Long term alcohol abuse is very harmful to people. But recent research shows that long term alcohol consumption can reduce the incidence of certain diseases in human beings. Therefore, the advantages and disadvantages of drinking are still controversial. The effects of alcohol on the life of the nematodes for a long time. The results showed that long term high concentration of alcohol (> 4%) shortened the life span of the nematode, reduced the number of spawns, and weakened the exercise ability. Interestingly, the long term low concentration of alcohol stimulation (1-2%) could prolong the life of the nematode. Although the number of eggs was reduced, the long-term 2% concentration of alcohol was stimulated. The life span of the nematode can be extended by about 2.76 days, with an extension of 14.53%, and the slowing of the aging of the movement. The study found that this effect is closely related to the insulin like signaling pathway and the transcription factor Sir-2.1 in the nematode. Compared to the unstimulated control group, the 2% alcohol stimulation from the egg, the larva and the adult can make the nematode in the nematode. This study demonstrated that the nematode is an excellent model for long-term alcohol stimulation and a long amount of alcohol stimulation can have a positive effect on the body. This study provides a further study of the effects of the long-term stimulation of alcohol on the physiological functions of human beings and the related molecular mechanisms. Basics.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R341

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 潘曉麗;張楠楠;葉紅蓮;趙月飛;高紅;;腓骨肌萎縮癥1型患兒肌電圖和遺傳學(xué)研究[J];中國當(dāng)代兒科雜志;2011年08期

2 張如旭;唐北沙;;腓骨肌萎縮癥的分子生物學(xué)研究進(jìn)展[J];國際神經(jīng)病學(xué)神經(jīng)外科學(xué)雜志;2006年03期

3 郭鵬;張保剛;王相斌;宋福聰;馮文霞;唐北沙;夏昆;;腓骨肌萎縮癥1型和2型的臨床與基因突變特點(diǎn)[J];河北醫(yī)藥;2011年23期

4 張社卿,喬德麗,蔣德科,鄭惠民,丁素菊,余龍;遺傳性運(yùn)動(dòng)感覺神經(jīng)病1家系[J];罕少疾病雜志;2005年03期

5 張?jiān)栖?浦道學(xué);雷進(jìn);王建林;童齡;;腓骨肌萎縮癥10例臨床與神經(jīng)電生理分析[J];臨床薈萃;2010年22期

6 張如旭,唐北沙,資曉宏,羅巍,潘乾,夏昆,湯建光,黃順祥;腓骨肌萎縮癥1A型的臨床、神經(jīng)電生理和疾病基因突變分析[J];臨床神經(jīng)病學(xué)雜志;2003年06期

7 張如旭,唐北沙,資曉宏,趙國華,張付峰,羅巍,夏昆,潘乾,文路,胡正茂,郭鵬;X連鎖腓骨肌萎縮癥Cx32基因的突變、臨床和電生理特點(diǎn)[J];臨床神經(jīng)病學(xué)雜志;2005年05期

8 鄒藝;劉英;李素榮;胥勛成;高國勛;;腓骨肌萎縮癥的臨床及神經(jīng)電生理特點(diǎn)分析[J];臨床神經(jīng)電生理學(xué)雜志;2008年05期

9 張楠楠;潘曉麗;;X-連鎖遺傳性腓骨肌萎縮癥的研究進(jìn)展[J];中國全科醫(yī)學(xué);2010年24期

10 朱斌;王恩多;;氨基酰-tRNA合成酶與神經(jīng)退行性疾病[J];生物化學(xué)與生物物理進(jìn)展;2007年06期

相關(guān)博士學(xué)位論文 前3條

1 羅巍;腓骨肌萎縮癥的疾病基因定位、NEFL基因突變分析及腦干聽覺誘發(fā)電位研究[D];中南大學(xué);2003年

2 李書劍;HSPB8蛋白與NEFL蛋白相互作用研究及HSPB8蛋白對細(xì)胞相對活力的影響[D];中南大學(xué);2007年

3 張付峰;HSP22轉(zhuǎn)基因小鼠模型的建立[D];中南大學(xué);2008年

相關(guān)碩士學(xué)位論文 前3條

1 劉婷;CMT2L型的轉(zhuǎn)基因小鼠模型的電生理學(xué)與病理學(xué)分析[D];中南大學(xué);2011年

2 高利國;兩個(gè)CMTX1家系的臨床及遺傳分析[D];山西醫(yī)科大學(xué);2007年

3 王歡;清開靈注射液及其中間品的類過敏反應(yīng)與細(xì)胞內(nèi)藥代動(dòng)力學(xué)研究[D];北京中醫(yī)藥大學(xué);2014年

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