丙二醛与丙酮醛对人骨髓间充质干细胞的生长和凋亡的影响

发布时间：2018-06-17 16:42

本文选题：活性羰基类物质 + 丙二醛　；参考：《湖南师范大学》2009年硕士论文

【摘要】： 活性羰基类物质(reactive carbonyl species,RCS)是脂质过氧化和非酶糖基化的共同中间产物,即使在健康组织中,它们也普遍存在,特别是不饱和醛酮,如:丙二醛(malondialdehyde,MDA),丙酮醛(methylglyoxal,MGO),4-羟基壬稀醛,3-脱氧葡糖醛酮和乙二醛等,它们在机体内能造成酶功能抑制,免疫功能紊乱,细胞膜损伤等广泛的病理生理变化。正是如此,羰基应激衰老学说认为:羰-氨反应是脂类和糖类两大能源物质新陈代谢过程中不可避免的生化副反应,它在体内能产生广泛而又缓慢的交联,最终造成体内蛋白、脂质、核酸等生物大分子的不可修复性损伤,从而加速衰老过程。人骨髓间充质干细胞(human bone marrow mesenchymal stem cells,hMSCs)是具有高度自我更新能力和多向分化潜能的一类成体干细胞,它参与了组织更新和损伤修复。随着年龄的增加,hMSCs在体内将逐渐出现数量减少和功能缺陷,从而与骨关节炎、骨质疏松症、动脉粥样硬化和糖尿病等多种衰老相关疾病的病理生理密切相关。MDA和MGO作为两种重要的RCS,它们分别是脂质过氧化和非酶糖基化的产物,MDA和MGO等多种RCS在循环中蓄积,与多种衰老相关疾病的形成相关。本文旨在研究MDA与MGO对hMSCs生长和凋亡的影响,揭示羰基应激对体外培养hMSCs的作用机理。先通过细胞分化、表面抗原分析、形态学观察鉴定细胞为hMSCs,然后用不同浓度的MDA与MGO处理hMSCs,以细胞计数法测定细胞生长曲线,MTT检测细胞活性,流式细胞仪分析细胞的凋亡百分率。结果发现:低浓度的MDA与MGO对hMSCs生长和凋亡没有显著影响,较高浓度MDA与MGO能显著抑制细胞的生长,导致群体倍增时间显著延长,细胞的存活率下降,凋亡细胞的百分率增加,且呈典型的剂量依赖关系。这些结果表明:MDA与MGO都易造成hMSCs的损伤,影响hMSCs的生长、代谢、增殖和诸多其它细胞功能,羰基应激可能是机体内一系列衰老相关的病理生理改变的重要原因。
[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.
【学位授予单位】：湖南师范大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R363

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