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超聲介導(dǎo)SDF-1α基因轉(zhuǎn)染急性心肌梗死大鼠心臟對(duì)非靶組織的影響

發(fā)布時(shí)間:2018-05-03 09:25

  本文選題:靶向微泡破壞技術(shù) + 基質(zhì)細(xì)胞衍生因子-1α; 參考:《新疆醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的:利用超聲靶向微泡破壞(Ultrasound targeted microbubble destruction,UTMD)技術(shù)介導(dǎo)外源性基因修復(fù)受損的靶器官和組織的研究正在加速發(fā)展,但基因轉(zhuǎn)染修復(fù)靶器官的同時(shí)對(duì)非靶組織的影響情況研究較少,而超聲、微泡及重組腺病毒聯(lián)合介導(dǎo)基因在非靶組織中的轉(zhuǎn)染未見(jiàn)報(bào)道,本研究旨在評(píng)價(jià)超聲、微泡及重組腺病毒聯(lián)合介導(dǎo)外源性基質(zhì)細(xì)胞衍生因子1α(Stromal Cell-derived Factor-1α,SDF-1α)基因轉(zhuǎn)染急性心肌梗死(Acute Myocardial Infarction,AMI)大鼠心臟時(shí)在非靶組織肝臟、肺臟及腎臟的轉(zhuǎn)染情況。方法:成功構(gòu)建AMI模型的40只SD大鼠按照查隨機(jī)數(shù)字表的方法將其完全隨機(jī)分為4組:單純超聲輻照組(M+U組/對(duì)照組,n=10);超聲輻照+載pAd-EGFP/SDF-1α(生物素化的共表達(dá)綠色熒光蛋白和SDF-1α的重組腺病毒)基因微泡給藥1天組(M+S1+U組,n=10)、連續(xù)給藥2天組(M+S2+U組,n=10)及連續(xù)給藥3天組(M+S3+U組,n=10)。AMI術(shù)后7天,激光共聚焦顯微鏡觀察非靶組織肝臟、肺臟及腎臟中綠色熒光蛋白的表達(dá)情況。結(jié)果:增強(qiáng)型綠色熒光蛋白分別在肺臟、肝臟及腎臟中的表達(dá)面積比如下(%area):M+U:0,0,0;M+S1+U:2.57±0.88,2.31±0.77,2.30±0.80;M+S2+U:2.97±0.94,2.89±1.00,2.77±0.82;M+S3+U:3.01±0.71,2.98±0.86,2.89±0.79。所有給藥組與對(duì)照組相比差異均具有統(tǒng)計(jì)學(xué)意義(P㩳0.05),但給藥一、二及三天組間差異無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論:超聲、微泡及重組腺病毒聯(lián)合介導(dǎo)外源性SDF-1α基因轉(zhuǎn)染AMI大鼠心臟的同時(shí),非靶組織肝臟、肺臟及腎臟也會(huì)被轉(zhuǎn)染,而且隨著給藥天數(shù)的增加,轉(zhuǎn)染亦呈增加趨勢(shì),但靶基因在非靶組織中的轉(zhuǎn)染與給藥天數(shù)并非呈線性相關(guān),即隨著給藥天數(shù)的增加,靶基因在非靶組織中的轉(zhuǎn)染并未產(chǎn)生顯著的累積效應(yīng)。
[Abstract]:Objective: the study of transgene repair of damaged target organs and tissues mediated by ultrasound targeted microbubble destruction of ultrasound targeted microbubble destructionwas accelerated, but the effect of gene transfection on non-target tissues was less studied. However, the transfection of genes mediated by ultrasound, microbubbles and recombinant adenovirus in non-target tissues has not been reported. Transfection of exogenous stromal Cell-derived Factor-1 偽 Cell-derived Factor-1 偽 -SDF-1 偽 gene into the heart of acute myocardial infarction (AMI) rats by microbubble and recombinant adenovirus in non-target liver, lung and kidney. Methods: forty SD rats who successfully constructed AMI model were randomly divided into 4 groups according to the method of random digital table: pure ultrasound irradiation group, mu group / control group, ultrasound irradiation pAd-EGFP/SDF-1 偽 (biotin coexpression green) Fluorescent protein and recombinant adenovirus of SDF-1 偽) gene microbubble administration group was treated with MS1U for 1 day, group M S 2 U for 2 days, group M S 3 U for 3 days, group M S 3 U for 7 days after operation, and group M S 3 U for 3 days for 7 days after operation. The expression of green fluorescent protein (GFP) in liver, lung and kidney was observed by confocal laser microscopy. Results: the expression areas of enhanced green fluorescent protein in lung, liver and kidney were as follows: a: M: M: U: 0: 0. M S1: U: 2.57 鹵0.88 鹵2.31 鹵0.80 MS2: 2.97 鹵0.94U 2.89 鹵1.002.77 鹵0.82mS3 U3.01 鹵0.71U: 2.98 鹵0.862.89 鹵0.79. Compared with the control group, the difference of all groups was statistically significant, but there was no significant difference between the first, second and third day of administration. Conclusion: ultrasound, microbubble and recombinant adenovirus mediated exogenous SDF-1 偽 gene transfection into the heart of AMI rats, while non-target liver, lung and kidney were also transfected, and the transfection showed an increasing trend with the increase of administration days. However, the transfection of target genes in non-target tissues was not linearly correlated with the days of administration, that is, the transfection of target genes in non-target tissues did not produce a significant cumulative effect with the increase of administration days.
【學(xué)位授予單位】:新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類(lèi)號(hào)】:R542.22;R445.1

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