【摘要】：本文用HUEVC體外血管生成模型,考察了硒雜環(huán)化合物(鄰菲Up琳硒二唑)對血管生成的影響,用體外酶活性動力模型評價(jià)了富硒螺旋藻多肽對血管緊張素轉(zhuǎn)化酶(ACE)的抑制作用,用動物實(shí)驗(yàn)及原代細(xì)胞培養(yǎng)研究了硒對巨噬細(xì)胞吞噬脂質(zhì)的影響。實(shí)驗(yàn)內(nèi)容和主要結(jié)果如下： 1采用細(xì)胞劃痕實(shí)驗(yàn)及體外血管生成技術(shù),檢測鄰菲Up琳硒二唑?qū)UEVC體外血管生成的影響。發(fā)現(xiàn)鄰菲Up琳硒二唑?qū)UEVC細(xì)胞的遷移有明顯抑制作用,且具有劑量效應(yīng)。進(jìn)而發(fā)現(xiàn),隨鄰菲Up琳硒二唑處理濃度的增加,在4-6μM時,血管樣結(jié)構(gòu)比空白對照組明顯變短、不完整,在8μM SePhen作用下,管狀結(jié)果崩解,細(xì)胞凋亡增加。 2嚴(yán)格硒營養(yǎng)控制復(fù)制小鼠低硒、適硒和高硒模型,分離誘導(dǎo)相應(yīng)不同硒營養(yǎng)狀況的骨髓來源巨噬細(xì)胞(BMDM),并分別以80、160、320ng/mL硒濃度進(jìn)行BMDM培養(yǎng),發(fā)現(xiàn)高硒營養(yǎng)水平對活化巨噬細(xì)胞硒酶活性、ROS生成有促進(jìn)作用,并且發(fā)現(xiàn)用低密度脂蛋白(LDL)處理BMDM5h后,介導(dǎo)脂質(zhì)內(nèi)吞的主要受體CD36在隨硒營養(yǎng)水平增加而明顯下調(diào),RT-PCR發(fā)現(xiàn)CD36mRNA水平隨硒營養(yǎng)水平提高有一定程度的上調(diào),但無統(tǒng)計(jì)顯著性。另外,無論蛋白水平還是mRNA水平均未檢測到硒營養(yǎng)對巨噬細(xì)胞脂質(zhì)攝取相關(guān)分子PPARγ有明顯影響。 綜上所述,鄰菲Up琳硒二唑在高濃度8μM下抑制細(xì)胞遷移和血管生成。亞硒酸鈉在高濃度下(320ng/mL)可能主要通過氧化還原平衡調(diào)節(jié)CD36降解,使巨噬細(xì)胞內(nèi)吞脂質(zhì)減少,對動脈粥樣硬化具有一定的防治意義。
[Abstract]:The effects of selenium heterocyclic compounds (o-phenanthroline selenediazole) on angiogenesis were investigated using HUEVC angiogenesis model in vitro. The inhibitory effects of selenium-enriched phycopeptides on angiotensin converting enzyme (ACE) were evaluated by using in vitro enzyme activity dynamic model. The effect of selenium on the phagocytosis of macrophages was studied by animal experiment and primary cell culture. The experimental contents and main results were as follows: 1 the effect of phenanthroline Up on HUEVC angiogenesis in vitro was detected by cell scratch test and in vitro angiogenesis technique. It was found that o-phenanthrene Up linoselenediazole inhibited the migration of HUEVC cells in a dose-dependent manner. It was further found that with the increase of the concentration of o-phenanthrene Up linoselenediazole, at 4-6 渭 M, the vasculoid structure became shorter and incomplete than that of the blank control group, and the tubular results disintegrated under the action of 8 渭 M SePhen. Cell apoptosis increased. 2 mice models of low selenium, suitable selenium and high selenium were established under strict selenium nutrition control. (BMDM), from bone marrow macrophages with different selenium status were isolated and cultured with 80160320ng/mL selenium concentration respectively. It was found that high selenium nutrition level promoted the production of Ros in activated macrophages, and that BMDM5h was treated with low density lipoprotein (LDL) (LDL). CD36, the main receptor of lipid endocytosis, was down-regulated by RT-PCR with the increase of selenium nutrition level. It was found that the level of CD36mRNA was up-regulated to some extent with the increase of selenium nutrition level, but there was no statistical significance. In addition, no significant effect of selenium on lipid uptake of PPAR 緯 in macrophages was found in either protein level or mRNA level. In conclusion, o-phenanthroline Up linselenediazole inhibited cell migration and angiogenesis at high concentration of 8 渭 M. Sodium selenite at high concentration (320ng/mL) may regulate the degradation of CD36 by redox equilibrium and decrease the endocytosis lipid of macrophages, which has a certain significance for the prevention and treatment of atherosclerosis.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R151

【參考文獻(xiàn)】

相關(guān)期刊論文 前6條

1 閻玉芹,李健群;硒缺乏與甲狀腺激素代謝[J];中國地方病防治雜志;1992年03期

2 鐘國贛,李云義,孫曉霞,江巖,陳羽,王小明;缺硒對離體大鼠工作心臟心肌收縮性能的影響[J];中國地方病學(xué)雜志;1991年04期

3 姜昕,曾和松,郭毅,周志斌,唐冰杉,李富康;The expression of matrix metalloproteinases-9, transforming growth factor-β1 and transforming growth factor-β receptorⅠ in human atherosclerotic plaque and their relationship with plaque stability[J];Chinese Medical Journal;2004年12期

4 夏敏;白書閣;白大芳;;硒對老齡雄性大鼠機(jī)體谷胱甘肽過氧化物酶、過氧化脂質(zhì)及其比值的影響[J];老年學(xué)雜志;1991年01期

5 黃峙,向軍儉,鄭文杰,郭寶江;鈍頂螺旋藻富集轉(zhuǎn)化硒及硒在藻體中的分布[J];植物生理學(xué)通訊;2001年01期

6 丁健;抗腫瘤藥物的研究新進(jìn)展[J];中國新藥雜志;2000年03期

，

本文編號：2234103