本文選題：CD47 + TSP1��； 參考：《吉林大學(xué)》2016年博士論文

【摘要】：隨著人口預(yù)期壽命的延長(zhǎng)和出生率的不斷降低,人口老齡化已成為日漸突出的社會(huì)現(xiàn)象。隨之帶來一系列社會(huì)和醫(yī)療相關(guān)的挑戰(zhàn),突出方面就是心血管疾病發(fā)生率的不斷升高。流行病學(xué)調(diào)查已證實(shí)老齡是心血管疾病的高危因素,研究顯示老齡人口血管功能受損,表現(xiàn)為血管順應(yīng)性下降,自我修復(fù)能力降低,最終導(dǎo)致動(dòng)脈粥樣硬化等血管疾病。其中的重要機(jī)制,就是內(nèi)皮細(xì)胞的老化。細(xì)胞的衰老是各種內(nèi)外環(huán)境壓力共同作用的結(jié)果。衰老細(xì)胞內(nèi)基因表達(dá)異于相對(duì)年輕細(xì)胞,導(dǎo)致細(xì)胞功能受損、分裂停止。內(nèi)皮細(xì)胞的老化原因多樣,主要是細(xì)胞不斷分裂及血液內(nèi)過氧化物的損傷,最終促進(jìn)動(dòng)脈粥樣硬化及血栓的形成。因此,延緩內(nèi)皮細(xì)胞的衰老可能在減少心血管疾病方面有著重大的意義。血小板反應(yīng)蛋白(thrombospondin-1,TSP1)是一種細(xì)胞基質(zhì)糖蛋白,最早發(fā)現(xiàn)以未活化形式儲(chǔ)存于血小板中,也可來源于內(nèi)皮細(xì)胞、成纖維細(xì)胞、平滑肌細(xì)胞等多種細(xì)胞類型。TSP1有多重結(jié)構(gòu)域,可與多種細(xì)胞表面受體結(jié)合,例如CD47、CD36、低密度脂蛋白受體相關(guān)蛋白1(LRP1)等。正常人體循環(huán)系統(tǒng)內(nèi)TSP1濃度僅有20?g/L,但對(duì)調(diào)節(jié)血管功能和內(nèi)環(huán)境穩(wěn)態(tài)卻有重要意義。近年來研究發(fā)現(xiàn),TSP1與配體CD47結(jié)合后可起到抑制內(nèi)皮細(xì)胞NO通路的作用,從而抑制血管舒張。此外,TSP1可通過拮抗血管內(nèi)皮生長(zhǎng)因子(VEGF)作用抑制血管新生,還可通過上調(diào)TGF-?水平從而促進(jìn)糖尿病相關(guān)動(dòng)脈粥樣硬化斑塊形成。有研究發(fā)現(xiàn),TSP1在衰老組織中表達(dá)上升,并推測(cè)可能與衰老生物體組織血供減少這一現(xiàn)象相關(guān)。CD47又稱為整合素相關(guān)蛋白(IAP),廣泛表達(dá)于多種組織細(xì)胞表面。CD47與巨噬細(xì)胞上的SIRPα結(jié)合后可保護(hù)細(xì)胞免于被巨噬細(xì)胞吞噬,與TSP1結(jié)合則可有效抑制內(nèi)皮細(xì)胞NO通路,介導(dǎo)血管收縮;還有研究顯示CD47與TSP1的多肽4N1K結(jié)合后可介導(dǎo)多種細(xì)胞死亡(包括人的腦微血管內(nèi)皮細(xì)胞),但具體機(jī)制不詳;最近有研究稱CD47缺失的小鼠肺內(nèi)皮細(xì)胞具有干細(xì)胞特性,可分化為多種組織細(xì)胞,具體機(jī)制仍不明了。我們?cè)谇捌谘芯恐邪l(fā)現(xiàn)CD47缺失的鼠腦微血管內(nèi)皮細(xì)胞具有更強(qiáng)的傳代能力,結(jié)合之前的文獻(xiàn)報(bào)道,我們考慮CD47-TSP1通路對(duì)內(nèi)皮細(xì)胞的衰老可能有一定的調(diào)控作用,而相關(guān)研究報(bào)道至今不明確,因此CD47-TSP1對(duì)內(nèi)皮細(xì)胞衰老調(diào)控及其機(jī)制具有很大的研究?jī)r(jià)值。首先,我們提取8周齡雌性CD47缺失及WT小鼠的腦微血管內(nèi)皮細(xì)胞作為研究對(duì)象,進(jìn)行cell counting kit-8(cck-8)、CFSE、Brd U、內(nèi)皮細(xì)胞成管等實(shí)驗(yàn),比較CD47缺失和WT小鼠內(nèi)皮細(xì)胞增殖能力及功能,從而判斷細(xì)胞衰老情況。隨后我們對(duì)細(xì)胞進(jìn)行連續(xù)傳代培養(yǎng),使用?-半乳糖苷酶(?-gal)染色(衰老細(xì)胞可被綠染),更直觀地對(duì)比細(xì)胞的衰老水平。進(jìn)而我們對(duì)兩組細(xì)胞TSP1表達(dá)水平進(jìn)行分析,明確TSP1表達(dá)在衰老細(xì)胞中的改變。接下來,我們對(duì)兩組細(xì)胞的細(xì)胞周期及其相關(guān)細(xì)胞周期抑制劑p53、p21、p16,細(xì)胞周期激酶CDK4、CDK6、Cyclin D1,下游E2F通路分子CDK1、CDK2等進(jìn)行分析,探究CD47對(duì)細(xì)胞衰老調(diào)控可能的機(jī)制。最后,為研究CD47-TSP1通路在內(nèi)皮細(xì)胞衰老調(diào)控中的作用,我們分別單獨(dú)加入TSP1及TSP1抗體,使用?-半乳糖苷酶染色、熒光定量等方法明確CD47-TSP1通路在內(nèi)皮細(xì)胞衰老中的作用。結(jié)果顯示:1、對(duì)CD47缺失及WT小鼠的血管內(nèi)皮細(xì)胞進(jìn)行cck-8、Brd U、CFSE等實(shí)驗(yàn)發(fā)現(xiàn),與WT相比,CD47缺失組內(nèi)皮細(xì)胞在相同生長(zhǎng)時(shí)間內(nèi)細(xì)胞數(shù)目、增殖細(xì)胞數(shù)目和分裂次數(shù)均更多,說明CD47缺失的內(nèi)皮細(xì)胞增殖能力更強(qiáng),而增殖能力強(qiáng)弱是細(xì)胞衰老水平判斷的重要指標(biāo),間接說明CD47缺失的內(nèi)皮細(xì)胞抵抗衰老的能力更強(qiáng)。2、通過體外成管實(shí)驗(yàn)(tube formation assay)發(fā)現(xiàn),CD47缺失組內(nèi)皮細(xì)胞無論在細(xì)胞年輕(第2代)還是年老(第6代)時(shí),成管能力均較WT組明顯增強(qiáng);將CD47缺失和WT組內(nèi)皮細(xì)胞分別與matrigel混合后打入小鼠皮下,發(fā)現(xiàn)CD47缺失組內(nèi)皮細(xì)胞與matrigel形成的團(tuán)塊含有更多的紅細(xì)胞及血管管腔,體外和體內(nèi)實(shí)驗(yàn)均表明CD47缺失組內(nèi)皮細(xì)胞功能較WT組更強(qiáng)。功能強(qiáng)弱同樣代表細(xì)胞的衰老程度,因此更進(jìn)一步說明CD47缺失的內(nèi)皮細(xì)胞抵抗衰老的能力更強(qiáng)。3、隨著細(xì)胞傳代,衰老細(xì)胞(?-gal染色陽性)比例不斷增多,細(xì)胞周期分析顯示S期細(xì)胞比例不斷降低,與WT組相比,CD47缺失組內(nèi)皮細(xì)胞?-gal染色陽性率較低,S期比例相對(duì)較高,說明CD47缺失組中衰老比例較低,表明在同等傳代次數(shù)下,CD47缺失的內(nèi)皮細(xì)胞衰老得到延緩;在兩組細(xì)胞中,TSP1表達(dá)均隨細(xì)胞傳代逐漸增多,說明TSP1可能在內(nèi)皮細(xì)胞衰老中起重要作用,而CD47缺失組衰老程度較低,結(jié)合CD47為TSP1的重要受體考慮,推測(cè)CD47-TSP1通路可能在內(nèi)皮細(xì)胞衰老中起到促進(jìn)作用,而這一作用可能通過細(xì)胞周期的調(diào)控來實(shí)現(xiàn)。進(jìn)一步對(duì)細(xì)胞周期抑制劑p53、p21、p16,細(xì)胞周期激酶CDK4、CDK6、Cyclin D1,下游E2F通路分子CDK1、CDK2等進(jìn)行分析,發(fā)現(xiàn)p53、p21、p16在WT組中高表達(dá),CDK4、CDK6、Cyclin D1,下游E2F通路分子CDK1、CDK2等在WT中低表達(dá),推測(cè)CD47-TSP1通路通過調(diào)控細(xì)胞周期中的關(guān)鍵分子來達(dá)到控制細(xì)胞周期的目的,從而實(shí)現(xiàn)對(duì)內(nèi)皮細(xì)胞衰老的調(diào)節(jié)。4、為證實(shí)TSP1在內(nèi)皮細(xì)胞衰老中具有促進(jìn)作用,我們?cè)诩?xì)胞培養(yǎng)體系中分別單獨(dú)添加TSP1蛋白及TSP1抗體,結(jié)果發(fā)現(xiàn)在年輕細(xì)胞的中(第2代),WT組添加TSP1蛋白可使?-gal染色陽性細(xì)胞比例增加,細(xì)胞成管能力變差,說明TSP1可促進(jìn)細(xì)胞衰老;在CD47缺失組中未觀察到此類現(xiàn)象,表明TSP1的作用是CD47介導(dǎo)實(shí)現(xiàn)的。而第2代細(xì)胞中,無論WT還是CD47缺失組,未發(fā)現(xiàn)TSP1抗體的添加與對(duì)照相比有顯著改變,考慮為2代細(xì)胞尚年輕的緣故,TSP1-CD47通路尚未充分激發(fā)。對(duì)年老細(xì)胞(第4代)添加TSP1抗體后發(fā)現(xiàn),WT組?-gal染色陽性細(xì)胞比例顯著降低,p53、p21、p16表達(dá)下降,CDK4、CDK6、Cyclin D1,下游E2F通路分子CDK1、CDK2等表達(dá)上升,說明拮抗TSP1作用可延緩細(xì)胞衰老,而CD47缺失組中未觀察到此類現(xiàn)象,更進(jìn)一步證實(shí)CD47-TSP1通路在內(nèi)皮細(xì)胞衰老中的促進(jìn)作用。綜上所述,我們研究得到的結(jié)論是:CD47-TSP1通路在內(nèi)皮細(xì)胞衰老中起促進(jìn)作用,這一作用可能通過對(duì)細(xì)胞周期的調(diào)控來實(shí)現(xiàn)。CD47-TSP1通路對(duì)細(xì)胞周期的調(diào)控是通過調(diào)節(jié)細(xì)胞周期抑制劑p53、p21、p16,細(xì)胞周期激酶CDK4、CDK6、Cyclin D1等細(xì)胞周期中的關(guān)鍵分子來實(shí)現(xiàn),CD47-TSP1通路可促進(jìn)細(xì)胞周期抑制劑并抑制細(xì)胞周期激酶表達(dá),從而抑制細(xì)胞周期進(jìn)行,最終促進(jìn)細(xì)胞衰老。研究結(jié)果表明,TSP1水平對(duì)心血管系統(tǒng)衰老程度具有提示作用,調(diào)控TSP1的表達(dá)在防治心血管疾病中具有重要意義。
[Abstract]:With the prolongation of the life expectancy and the decreasing of the birth rate, the aging of the population has become an increasingly prominent social phenomenon. With a series of social and medical related challenges, the incidence of cardiovascular disease is increasing. Epidemiological investigation has confirmed that aging is a high risk factor for cardiovascular disease. The damage of vascular function in the aged population shows that the vascular compliance decreases, the ability of self repair is reduced, and the vascular diseases such as atherosclerosis are caused by the aging of endothelial cells. The aging of the cells is the result of the interaction of various internal and external environmental pressures. The cell function is damaged and the division stops. The aging causes of endothelial cells are various, mainly cell division and blood peroxide damage, which ultimately promote atherosclerosis and thrombosis. Therefore, the delay of endothelial cell aging may be of great significance in reducing cardiovascular disease. (thrombospondin-1, TSP1) is a cell matrix glycoprotein, which was first found in unactivated forms of platelets, or derived from endothelial cells, fibroblasts, smooth muscle cells, and many other cell types,.TSP1 with multiple domains, such as CD47, CD36, low density lipoprotein receptor related proteins. 1 (LRP1) and so on. The concentration of TSP1 in normal human circulation system is only 20? G/L, but it is important for regulating vascular function and homeostasis. In recent years, it has been found that TSP1 and ligand CD47 can inhibit the NO pathway of endothelial cells and inhibit vasodilatation. In addition, TSP1 can be used to antagonize vascular endothelial growth factor (VEGF). By inhibiting angiogenesis, it can also promote the formation of atherosclerotic plaques related to diabetes by increasing the TGF-? Levels. Studies have found that the expression of TSP1 in senescent tissues is increased, and that it may be associated with the decrease of blood supply in aging organisms..CD47 is also called integrin related protein (IAP), widely expressed in a variety of tissues. The binding of.CD47 on the cell surface and SIRP alpha on macrophages protects the cells from being phagocytic by macrophages. Binding to TSP1 can effectively inhibit the NO pathway of endothelial cells and mediate the vasoconstriction. There are also studies showing that CD47 and TSP1 polypeptide 4N1K can mediate multiple cell deaths (including human brain microvascular endothelial cells), but the specific mechanism is specific. We have recently found that CD47 missing mouse lung endothelial cells have the characteristics of stem cells and can differentiate into a variety of tissue cells. The specific mechanism is still unknown. In our previous study, we found that the CD47 deficient rat brain microvascular endothelial cells have a stronger generation ability. We consider the CD47-TSP1 pathway to the endothelium. Cell aging may have a certain regulatory role, and the related research reports are not clear so far, so CD47-TSP1 has great research value on the regulation and mechanism of endothelial cell aging. First, we extract 8 weeks old female CD47 deletion and WT mouse brain microvascular endothelial cells as the research object, and carry out cell counting kit-8 (CCK-8), CF SE, Brd U, endothelial cell formation and so on, compared CD47 deletion and proliferation and function of WT mouse endothelial cells to judge cell aging. Then we carried out continuous subculture of cells, using? - galactosidase (? -gal) staining (aging cells can be green), more intuitively compared cell senescence level. And then we to two groups The expression level of cell TSP1 was analyzed to identify the changes in TSP1 expression in senescent cells. Next, we analyzed the cell cycle of two groups and related cell cycle inhibitors p53, p21, p16, cell cycle kinase CDK4, CDK6, Cyclin D1, downstream E2F pathway molecule CDK1, CDK2 and so on. Finally, in order to study the role of the CD47-TSP1 pathway in the regulation of endothelial cell senescence, we separately added TSP1 and TSP1 antibodies, using galactosidase staining, and fluorescence quantitative methods to determine the role of CD47-TSP1 pathway in endothelial cell aging. Results: 1, CCK-8, Brd in CD47 deletion and WT mice endothelial cells. U, CFSE and other experiments found that compared with WT, the number of cells, the number of proliferating cells and the number of splits of the endothelial cells in the CD47 deletion group were more in the same time of growth, indicating that the proliferation ability of the endothelial cells with the CD47 deletion was stronger and the proliferation ability was the important index of the cell aging level, which indirectly indicated that the CD47 missing endothelial cells resisted and declined. The old ability of.2 was stronger. Through the tube formation assay test, it was found that the endothelial cells in the CD47 deletion group increased obviously in the young (second generation) or the old (sixth generation) groups. The CD47 deletion and the WT group endothelial cells were mixed with Matrigel in the mice subcutaneously, and the CD47 deletion group of endothelial cells was found. The group formed with Matrigel contained more red cells and vascular lumen. In vitro and in vivo, the function of endothelial cells in the CD47 deletion group was stronger than that of the WT group. The function strength also represented the senescence of the cells. Therefore, it further indicated that the endothelial cells with CD47 deletion were more capable of resisting senescence,.3, with cell passage, senescent cells ( The proportion of -gal staining positive) increased continuously. Cell cycle analysis showed that the proportion of S cells decreased continuously. Compared with group WT, the positive rate of -gal staining in CD47 deletion group was lower and the proportion of S phase was relatively high, indicating that the proportion of senescence in the CD47 deletion group was lower, indicating that under the same passages, the endothelial cell senescence missing CD47 was delayed; the aging of CD47 missing endothelial cells was delayed; In the two groups, the expression of TSP1 increased gradually with the cell passage, indicating that TSP1 may play an important role in the aging of endothelial cells, while the senescence of CD47 deletion group is low. Considering that CD47 is an important receptor for TSP1, it is presumed that the CD47-TSP1 pathway may play a role in the aging of endothelial cells, and this effect may be through the cell cycle. Further study the cell cycle inhibitors p53, p21, p16, cell cycle kinase CDK4, CDK6, Cyclin D1, and the downstream E2F pathway molecule CDK1, CDK2 and so on. In order to achieve the purpose of controlling cell cycle, the key molecules can realize the regulation of endothelial cell senescence. In order to confirm that TSP1 can promote the aging of endothelial cells, we added TSP1 protein and TSP1 antibody separately in the cell culture system. The results found that in the year light cells (second generations), the WT group added TSP1 protein. The proportion of -gal staining positive cells increased and the cell formation of cells became poor, indicating that TSP1 could promote cell senescence. No such phenomenon was observed in the CD47 deletion group, indicating that the effect of TSP1 was mediated by CD47. In the second generation cells, no matter the WT or the CD47 deletion group, the addition of the TSP1 anti body was significantly changed compared with the control, considering the 2 generation. After the cells were young, the TSP1-CD47 pathway was not fully stimulated. After adding TSP1 antibodies to the aged cells (fourth generation), the proportion of WT group -gal staining positive cells decreased significantly, the expression of p53, p21, p16 decreased, CDK4, CDK6, Cyclin D1, downstream E2F pathways and other expressions increased, indicating that the antagonistic effect could delay cell senescence. This phenomenon is not observed in the missing group and further confirms the role of the CD47-TSP1 pathway in the aging of endothelial cells. To sum up, we have concluded that the CD47-TSP1 pathway plays a role in the aging of endothelial cells, which may be mediated by the regulation of the cell cycle to achieve the cell cycle of the.CD47-TSP1 pathway. The regulation is realized by regulating key molecules in cell cycle, such as cell cycle inhibitor p53, p21, p16, cell cycle kinase CDK4, CDK6, Cyclin D1 and so on. CD47-TSP1 pathway can promote cell cycle inhibitors and inhibit cell cycle kinase expression, thus inhibiting cell cycle and eventually promoting cell senescence. The results show TSP1 water. Ping has a suggestive effect on the aging of the cardiovascular system. Regulating the expression of TSP1 is of great importance in the prevention and treatment of cardiovascular diseases.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R54

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5 殷觀梅;;血管內(nèi)皮細(xì)胞生長(zhǎng)抑制因子研究進(jìn)展[J];河北醫(yī)藥;2008年12期

6 劉寶宜,陳鐵鎮(zhèn),張寶庚,宋繼業(yè);動(dòng)脈粥樣硬化形成過程中內(nèi)皮細(xì)胞病變的研究(摘要)——主動(dòng)脈內(nèi)皮細(xì)胞平掙,掃描電鏡及透射電鏡的觀察[J];中國(guó)醫(yī)科大學(xué)學(xué)報(bào);1981年S1期

7 劉寶宜,陳鐵鎮(zhèn),張寶庚,宋繼業(yè);動(dòng)脈粥樣硬化形成過程中內(nèi)皮細(xì)胞的形態(tài)學(xué)變化的研究(主動(dòng)脈內(nèi)皮細(xì)胞平鋪技術(shù),掃描電鏡及透射電鏡的方法)[J];中國(guó)醫(yī)科大學(xué)學(xué)報(bào);1982年03期

8 張連元;;動(dòng)脈粥樣硬化發(fā)病機(jī)理中平滑肌和內(nèi)皮細(xì)胞的機(jī)能[J];煤礦醫(yī)學(xué);1983年04期

9 劉懷瓊;李德馨;;內(nèi)皮細(xì)胞的功能與休克的關(guān)系[J];國(guó)外醫(yī)學(xué).麻醉學(xué)與復(fù)蘇分冊(cè);1985年04期

10 何澤涌;;關(guān)于內(nèi)皮細(xì)胞研究的某些進(jìn)展[J];山西醫(yī)藥雜志;1987年03期

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8 苑t，

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