本文選題：活性羰基類物質(zhì) + 丙二醛�。� 參考：《湖南師范大學(xué)》2009年碩士論文

【摘要】： 活性羰基類物質(zhì)(reactive carbonyl species,RCS)是脂質(zhì)過氧化和非酶糖基化的共同中間產(chǎn)物,即使在健康組織中,它們也普遍存在,特別是不飽和醛酮,如:丙二醛(malondialdehyde,MDA),丙酮醛(methylglyoxal,MGO),4-羥基壬稀醛,3-脫氧葡糖醛酮和乙二醛等,它們?cè)跈C(jī)體內(nèi)能造成酶功能抑制,免疫功能紊亂,細(xì)胞膜損傷等廣泛的病理生理變化。正是如此,羰基應(yīng)激衰老學(xué)說認(rèn)為:羰-氨反應(yīng)是脂類和糖類兩大能源物質(zhì)新陳代謝過程中不可避免的生化副反應(yīng),它在體內(nèi)能產(chǎn)生廣泛而又緩慢的交聯(lián),最終造成體內(nèi)蛋白、脂質(zhì)、核酸等生物大分子的不可修復(fù)性損傷,從而加速衰老過程。 人骨髓間充質(zhì)干細(xì)胞(human bone marrow mesenchymal stem cells,hMSCs)是具有高度自我更新能力和多向分化潛能的一類成體干細(xì)胞,它參與了組織更新和損傷修復(fù)。隨著年齡的增加,hMSCs在體內(nèi)將逐漸出現(xiàn)數(shù)量減少和功能缺陷,從而與骨關(guān)節(jié)炎、骨質(zhì)疏松癥、動(dòng)脈粥樣硬化和糖尿病等多種衰老相關(guān)疾病的病理生理密切相關(guān)。MDA和MGO作為兩種重要的RCS,它們分別是脂質(zhì)過氧化和非酶糖基化的產(chǎn)物,MDA和MGO等多種RCS在循環(huán)中蓄積,與多種衰老相關(guān)疾病的形成相關(guān)。本文旨在研究MDA與MGO對(duì)hMSCs生長和凋亡的影響,揭示羰基應(yīng)激對(duì)體外培養(yǎng)hMSCs的作用機(jī)理。 先通過細(xì)胞分化、表面抗原分析、形態(tài)學(xué)觀察鑒定細(xì)胞為hMSCs,然后用不同濃度的MDA與MGO處理hMSCs,以細(xì)胞計(jì)數(shù)法測定細(xì)胞生長曲線,MTT檢測細(xì)胞活性,流式細(xì)胞儀分析細(xì)胞的凋亡百分率。結(jié)果發(fā)現(xiàn):低濃度的MDA與MGO對(duì)hMSCs生長和凋亡沒有顯著影響,較高濃度MDA與MGO能顯著抑制細(xì)胞的生長,導(dǎo)致群體倍增時(shí)間顯著延長,細(xì)胞的存活率下降,凋亡細(xì)胞的百分率增加,且呈典型的劑量依賴關(guān)系。這些結(jié)果表明:MDA與MGO都易造成hMSCs的損傷,影響hMSCs的生長、代謝、增殖和諸多其它細(xì)胞功能,羰基應(yīng)激可能是機(jī)體內(nèi)一系列衰老相關(guān)的病理生理改變的重要原因。
[Abstract]:Reactive carbonyl speciesics are common intermediates of lipid peroxidation and nonenzymatic glycosylation, and are common even in healthy tissues, especially unsaturated aldehydes and ketones. For example, malondialdehyde (malondialdehyde), malondialdehyde (malondialdehyde) (MDAA), pyruvate aldehyde-methylglyoxalen (MGOA), 4-hydroxynonanilic aldehydes, 3-deoxyglucosaldehyde-ketone (3-deoxyglucalanone) and Glyoxal (Glyoxal) can cause a wide range of pathophysiological changes such as inhibition of enzyme function, disorder of immune function and cell membrane damage. Therefore, carbonyl stress senescence theory holds that carbonyl-ammonia reaction is an inevitable biochemical side effect in the metabolism of lipid and carbohydrate, and it can produce extensive and slow crosslinking in the body, resulting in protein in the body. Lipid, nucleic acid and other biological macromolecules irreparable damage, thus accelerating the aging process. Human bone marrow mesenchymal stem cells (bone marrow mesenchymal stem cells) is a kind of adult stem cells with high self-renewal ability and multi-differentiation potential. It is involved in tissue regeneration and injury repair. With the increase of age, the number of hMSCs in vivo will gradually decrease and function defects, thus associated with osteoarthritis, osteoporosis, As two important RCSs, the pathophysiology of various aging related diseases, such as atherosclerosis and diabetes, is closely related to MDA and MGO, which are the products of lipid peroxidation and non-enzymatic glycosylation. Related to the formation of many aging related diseases. The purpose of this study was to investigate the effects of MDA and MGO on the growth and apoptosis of hMSCs and to reveal the mechanism of carbonyl stress on hMSCs cultured in vitro. The cells were identified as hMSCs by cell differentiation, surface antigen analysis and morphological observation. Then hMSCs were treated with different concentrations of MDA and MGO. Cell growth curve MTT was used to detect the cell activity. The percentage of apoptosis was analyzed by flow cytometry. The results showed that low concentrations of MDA and MGO had no significant effect on the growth and apoptosis of hMSCs, but higher concentrations of MDA and MGO could significantly inhibit the growth of hMSCs, and lead to a significant prolongation of population doubling time, a decrease in cell survival rate and an increase in the percentage of apoptotic cells. There is a typical dose-dependent relationship. These results suggest that both MGO and MGO can easily damage hMSCs and affect their growth, metabolism, proliferation and many other cellular functions. Carbonyl stress may be an important cause of a series of senescence related pathophysiological changes.
【學(xué)位授予單位】：湖南師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R363

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 陳菁菁;方垂;李芳序;朱澤瑞;印大中;;丙二醛對(duì)大鼠空間學(xué)習(xí)、記憶能力及海馬CA1區(qū)超微結(jié)構(gòu)的影響[J];動(dòng)物學(xué)報(bào);2007年06期

2 李海紅;付小兵;張慶紅;周崗;孫同柱;;人骨髓間充質(zhì)干細(xì)胞定向誘導(dǎo)分化為脂肪細(xì)胞[J];創(chuàng)傷外科雜志;2006年01期

3 康非吾,吳正華,黃欣,唐休發(fā),溫玉明;人骨髓間充質(zhì)干細(xì)胞的分離培養(yǎng)及向成骨細(xì)胞定向分化的實(shí)驗(yàn)研究[J];口腔頜面外科雜志;2004年04期

4 李國林,印大中;衰老分子生物化學(xué)中的羰基應(yīng)激[J];生命科學(xué)研究;2003年02期

5 梁敏,侯凡凡,易朝輝,張訓(xùn),劉志強(qiáng),易朝輝;甲基乙二醛對(duì)人血管內(nèi)皮細(xì)胞的毒性作用[J];中華腎臟病雜志;2002年05期

6 印大中;衰老:生命與熵增之戰(zhàn)[J];中國老年學(xué)雜志;2003年09期

7 彭艷華;王躍;;細(xì)胞衰老與機(jī)體老化關(guān)系的研究進(jìn)展[J];中國老年學(xué)雜志;2008年09期

，

本文編號(hào)：2031705