本文選題：糖尿病足潰瘍　切入點(diǎn)：天然多糖　出處：《天津醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的近年來糖尿病發(fā)病率逐年攀升,長(zhǎng)期血糖增高導(dǎo)致大血管、微血管受損并危及心、腦、腎、周圍神經(jīng)、眼睛、足等。糖尿病足潰瘍作為糖尿病嚴(yán)重并發(fā)癥之一,其病程反復(fù)、難愈合且有極高的致殘率,給患者和家屬帶來極大的痛苦和沉重的經(jīng)濟(jì)負(fù)擔(dān)。40%-80%的糖尿病足潰瘍會(huì)合并感染,會(huì)加重潰瘍治療的難度。隨抗生素的不斷泛用和濫用,多重耐藥菌的出現(xiàn)致使感染越來越難以控制。糖尿病足潰瘍周圍血液灌流受阻,抗菌藥物在潰瘍面的藥物濃度低,難以達(dá)到抗感染的效果。針對(duì)這一難題,本文旨在合成一種抗菌且不誘導(dǎo)細(xì)菌耐藥性的新型水凝膠傷口敷料,控制潰瘍面細(xì)菌感染,促進(jìn)傷口的愈合。方法將半胱氨酸接枝天然堿性多糖殼聚糖(CS-NAc)和馬來酸苷接枝葡聚糖(Dex-Ma)加入納米銀(AgNPs)溶液中,構(gòu)筑出三維網(wǎng)狀結(jié)構(gòu)的抗菌水凝膠。通過紅外光譜(FT-IR)和核磁譜圖分析材料結(jié)構(gòu),運(yùn)用掃描電鏡(SEM)觀察抗菌水凝膠的微觀結(jié)構(gòu),并通過溶脹測(cè)試來分析材料親水性能,細(xì)胞毒性測(cè)試來評(píng)估材料的生物相容性,LIVE/DEAD細(xì)菌熒光染色測(cè)試用以評(píng)估材料抗菌性能。進(jìn)一步以糖尿病大鼠全層皮膚缺損感染傷口為模型,觀察材料對(duì)感染傷口的愈合作用,并取傷口處肉芽組織做組織形態(tài)學(xué)分析和免疫組織化學(xué)檢測(cè),分析巨噬細(xì)胞因子特異性抗原CD68和標(biāo)記T細(xì)胞的因子CD3,評(píng)估傷口處的免疫能力及對(duì)炎癥的防御能力。結(jié)果實(shí)驗(yàn)測(cè)定巰基化殼聚糖巰基含量和馬來酸葡聚糖取代度,通過調(diào)節(jié)巰基與馬來雙鍵的摩爾比,在一定濃度AgNPs溶液條件下,制備含納米銀的天然多糖水凝膠(AgNPs@CNDM)水凝膠。掃描電鏡圖顯示凝膠具有孔洞大小均一的三維網(wǎng)絡(luò)結(jié)構(gòu);在5 min內(nèi),該復(fù)合凝膠溶脹率可達(dá)到400%,利用其溶脹性,可以迅速吸收組織滲液,有利于傷口愈合;細(xì)胞毒性測(cè)試結(jié)果顯示,與AgNPs相比,細(xì)胞與AgNPs@CNDM水凝膠浸出液共培養(yǎng)48 h后,細(xì)胞存活率均大于80%,這可能是該復(fù)合凝膠能起到緩釋Ag離子的作用,從而改善納米銀毒性,改善材料的安全性�？咕鷮�(shí)驗(yàn)結(jié)果表明,AgNPs@CNDM對(duì)金黃色葡萄球菌和銅綠假單孢菌均具有顯著的抗菌效果。在糖尿病大鼠感染傷口模型實(shí)驗(yàn)中,AgNPs@CNDM組不僅可以有效地抑制感染還可以加速傷口的愈合,組織形態(tài)學(xué)進(jìn)一步證實(shí)AgNPs@CNDM水凝膠對(duì)糖尿病大鼠感染傷口的抗炎促愈合作用。免疫組織化學(xué)檢測(cè)表明,AgNPs@CNDM水凝膠可以提高CD68和CD3因子的表達(dá),能在炎癥早期階段激活巨噬細(xì)胞,抑制炎癥控制感染,提高糖尿病大鼠傷口的局部免疫能力,加速傷口愈合。結(jié)論本文通過簡(jiǎn)單、便捷方法制備出的三維結(jié)構(gòu)天然多糖復(fù)合抗菌水凝膠,該凝膠具有較好的溶脹性能,可保持創(chuàng)面的濕性修復(fù)環(huán)境,且具有優(yōu)良的生物相容性,并能有效地抑制細(xì)菌的增殖,對(duì)免疫因子CD68和CD3表達(dá)具有上調(diào)功能,促進(jìn)感染傷口的愈合,且不誘導(dǎo)細(xì)菌耐藥的產(chǎn)生,為臨床治療糖尿病足潰瘍感染提供新策略和新思路。
[Abstract]:In recent years the incidence of diabetes is increasing year after year, long-term hyperglycemia leads to large blood vessels, microvascular damage and endanger the heart, brain, kidney, peripheral nerves, eyes, feet. Diabetic foot ulcer is one of the serious complications of diabetes mellitus, the duration of healing and relapse, with high morbidity, diabetic foot ulcer for patients and their families great pain and heavy economic burden of.40%-80% associated with infection, will increase the difficulty of treatment. With the continuous ulcer pan antibiotics use and abuse, resulting in the emergence of multiple drug resistant infection is becoming increasingly difficult to control diabetic foot ulcer. Peripheral blood perfusion is blocked, antibiotics in ulcer surface drug concentration is low, it is difficult to achieve anti the effect of infection. Aiming at this problem, this paper aims to synthesize a novel antibacterial hydrogel wound dressing without inducing bacterial resistance, the ulcer control bacterial infection, promote wound Healing. Methods the cysteine grafted natural alkaline polysaccharide chitosan (CS-NAc) and maleic acid grafted dextran (Dex-Ma) nano silver (AgNPs) solution, build a three-dimensional network structure. The antibacterial hydrogel by infrared spectroscopy (FT-IR) and NMR spectra analysis of the material structure, using scanning electron microscopy (SEM) microstructure observation of antibacterial hydrogel, and by swelling test to analyze the hydrophilic properties of materials, cell toxicity test to evaluate the biocompatibility of LIVE/DEAD bacterial staining testing to evaluate the antibacterial function of diabetic rats. Further to full-thickness skin defect wound infection model, observation materials on infected wound healing and wound at the granulation tissue for morphological analysis and immunohistochemistry analysis, factor CD3 factor macrophage specific antigen CD68 and T cell markers, the evaluation of the wound Immunity and inflammation on defense. Results the determination of thiolated chitosan sulfhydryl content and maleic acid dextran substitution, by regulating the molar ratio of thiol and maleic double bonds, in a certain concentration of AgNPs solution under natural conditions, polysaccharide gel preparation containing silver nanoparticles (AgNPs@CNDM) hydrogel. The SEM shows that the three-dimensional network structure gel holes with uniform size; within 5 min, the composite gel swelling rate can reach 400%, the swelling, can rapidly absorb tissue fluid, is conducive to wound healing; cell toxicity test results showed that compared with AgNPs cells and AgNPs@CNDM hydrogel extracts 48 h after co culture, cell survival rate more than 80%, it is possible that the composite gel can play the role of Ag + release, thereby improving the nano silver toxicity, improve the safety of antibacterial materials. The experimental results show that the AgNPs@CNDM of golden yellow Staphylococcus aureus and Pseudomonas aeruginosa had significant antibacterial effect in diabetic rats. The wound infection model experiment, AgNPs@CNDM group can not only effectively inhibit infection can accelerate wound healing, tissue morphology further confirmed that AgNPs@CNDM hydrogel promote healing of diabetic rats infected wounds anti-inflammatory. Immunohistochemistry showed that AgNPs@CNDM the hydrogel can improve the expression of CD68 and CD3 factor, can activate macrophages in the early stage of inflammation, inhibiting the inflammatory infection control, improve the local immunity wound in diabetic rats, accelerate wound healing. The conclusion of this paper through the simple and convenient preparation method of the three-dimensional structure of natural polysaccharide composite antibacterial gel, the gel has good swelling properties can keep wet, repair wound environment, and has excellent biocompatibility, and can effectively inhibit bacteria Proliferation plays an up-regulation role in the expression of CD68 and CD3, and promotes wound healing, and does not induce bacterial resistance. It provides new strategies and new ideas for clinical treatment of diabetic foot ulcer infection.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R587.2

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相關(guān)期刊論文 前2條

1 Leila Yazdanpanah;Morteza Nasiri;Sara Adarvishi;;Literature review on the management of diabetic foot ulcer[J];World Journal of Diabetes;2015年01期

2 Angela D.Liese;Xiaoguang Ma;David M.Maahs;Jennifer L.Trilk;;Physical activity,sedentary behaviors,physical fitness,and their relation to health outcomes in youth with type 1 and type 2 diabetes:A review of the epidemiologic literature[J];Journal of Sport and Health Science;2013年01期

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本文編號(hào)：1614391