本文選題：肝素明膠偶聯(lián)物　切入點(diǎn)：氧化聚古洛糖醛酸　出處：《天津大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：應(yīng)用仿細(xì)胞外基質(zhì)(ECM)思路設(shè)計(jì)的水凝膠,負(fù)載外源性生長因子后可直接作用于缺血性患處,在體內(nèi)降解過程中不斷釋放出生長因子而刺激細(xì)胞增殖、血管形成以及組織修復(fù),從而實(shí)現(xiàn)治療性血管的形成。本文制備了肝素明膠偶聯(lián)物(HGC),并采用氧化聚古洛糖醛酸(PAG)水凝膠作為仿ECM載體,探討了HGC保護(hù)的堿性成纖維細(xì)胞生長因子(bFGF)從水凝膠中的釋放行為,并通過雞胚絨毛尿囊膜(CAM)模型和大鼠背部皮下氣囊模型評(píng)價(jià)了其血管化性能。 通過酸性水解法用海藻酸鈉制備了聚古洛糖醛酸(PG),而后以低溫高碘酸鈉氧化法制備出PAG。通過酰胺化反應(yīng)向明膠引入了外源性氨基,從而提高了其反應(yīng)活性。將肝素偶聯(lián)到明膠側(cè)鏈上,形成了結(jié)構(gòu)類似于蛋白聚糖的HGC,而后將結(jié)合有bFGF的HGC、PAG以及氨基化明膠共交聯(lián)形成了PAG水凝膠。結(jié)果顯示,與海藻酸鹽水凝膠相比,PAG水凝膠的降解速率明顯減緩;肝素/bFGF重量比為2000時(shí)即可保證bFGF物理固定于PAG水凝膠網(wǎng)絡(luò)中,并使其緩慢釋放,證實(shí)HGC成分的加入對PAG水凝膠體系作為生長因子載體的重要性。 CAM模型結(jié)果顯示,PAG水凝膠體系中HGC和bFGF的加入量對CAM血管形成有著顯著的影響。0.5% HGC的加入量可以有效地保留bFGF的生物活性,從而促進(jìn)新生血管的形成。bFGF和內(nèi)皮細(xì)胞生長因子(VEGF)的協(xié)同作用對CAM血管形成有著明顯的促進(jìn)作用。大鼠背部皮下氣囊模型結(jié)果顯示,PAG水凝膠體系中HGC和bFGF的加入量對血管形成同樣有著重要的影響,1% HGC的加入量可以有效地促進(jìn)新生血管的形成,而水凝膠中的bFGF濃度達(dá)到100 ng/mL后,再繼續(xù)增加bFGF濃度時(shí)所形成的血管密度反而降低。
[Abstract]:The hydrogels designed with ECM mimic extracellular matrix can directly act on ischemic affected areas after loading exogenous growth factors, and release growth factors to stimulate cell proliferation, angiogenesis and tissue repair during degradation in vivo. In this paper, the heparin gelatin conjugate HGCX was prepared, and the oxidized polyuronic acid hydrogel was used as the imitating ECM carrier. The release behavior of basic fibroblast growth factor (bFGF) protected by HGC from hydrogels was investigated. The vascularization properties were evaluated by chicken embryo chorioallantoic membrane (chorioallantoic) model and rat dorsal subcutaneous balloon model. Polyglumuronic acid (PGN) was prepared by acid hydrolysis with sodium alginate, and then PAG was prepared by oxidation of sodium periodate at low temperature. Exogenous amino groups were introduced into gelatin by amidation reaction. By coupling heparin to the side chain of gelatin, HGCs with similar structure to proteoglycan were formed, and then PAG hydrogels were co-crosslinked with bFGF and amino gelatin. When the weight ratio of heparin / bFGF is 2000, the bFGF can be physically immobilized in the PAG hydrogel network and released slowly. The importance of the addition of HGC to the PAG hydrogel system as a growth factor carrier was confirmed. The results of CAM model showed that the addition of HGC and bFGF in PAG hydrogel system had a significant effect on CAM angiogenesis. The addition of 0.5% HGC could effectively preserve the biological activity of bFGF. Therefore, the synergistic effect of bFGF and endothelial growth factor (VEGF) on CAM angiogenesis was found. The results of rat dorsal subcutaneous balloon model showed that HGC and bFGF were added into PAG hydrogel system. The addition of 1% HGC can effectively promote angiogenesis. However, when the concentration of bFGF in the hydrogel reached 100 ng/mL, the vascular density decreased when the concentration of bFGF continued to increase.
【學(xué)位授予單位】：天津大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.0

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 王琴梅;廖燕紅;滕偉;廖志群;何圣清;許嘉琪;葉惠蘭;;鹽酸羥胺-電位滴定法測定氧化海藻酸鈉上的醛基濃度[J];分析試驗(yàn)室;2008年S1期

2 戴榮華;李林;曲巍;門振;;雞胚絨毛尿囊膜血管新生的研究進(jìn)展[J];廊坊師范學(xué)院學(xué)報(bào)(自然科學(xué)版);2009年02期

3 李沁華;;組織工程天然生物材料支架的特征[J];中國臨床康復(fù);2006年29期

4 龍娜;呂竹芬;;微球緩釋系統(tǒng)的突釋現(xiàn)象及其影響因素[J];中國藥師;2010年03期

相關(guān)博士學(xué)位論文 前1條

1 花中東;肝素誘導(dǎo)新生大白鼠肺血管成熟的研究[D];中國協(xié)和醫(yī)科大學(xué);2007年

，

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