發(fā)布時(shí)間：2018-06-08 18:26

  本文選題：CT + 造影劑�。� 參考：《吉林大學(xué)》2014年博士論文

【摘要】：目的： 合成一種新型納米CT造影Yb(OH)CO3并對(duì)其樣本進(jìn)行表征。研究Yb(OH)CO3作為CT造影劑的毒性，同時(shí)研究該造影劑在小鼠體內(nèi)分布和代謝情況。為其臨床應(yīng)用提供可行性依據(jù)。 材料與方法： （1）納米粒子Yb(OH)CO3的制備與表征：納米粒子Yb(OH)CO3的制備是由一個(gè)以尿素為基礎(chǔ)的均相沉淀過程。將Yb(NO3)3·5H2O(7.5mmol)和尿素(15g)溶解到去離子水中，并使溶液的總體積達(dá)到500ml。將上述溶液在室溫條件下使用磁力攪拌器攪拌2小時(shí)使溶液達(dá)到均勻。然后，將所得的均勻溶液90℃油浴3小時(shí)。后將所得到的懸浮液通過離心分離，得到的產(chǎn)物為白色粉末，用紗布包好后放入索氏提取器中，先用去離子水洗3-4遍，再用乙醇清洗3-4遍后，在60℃恒溫條件下真空烘箱中抽真空24小時(shí)，以備后續(xù)實(shí)驗(yàn)研究用。應(yīng)用掃描電鏡(SEM)、透射電鏡(TEM)、X-射線衍射(XRD)分析對(duì)樣本進(jìn)行表征。 （2）體外毒性實(shí)驗(yàn)：應(yīng)用MTT方法進(jìn)行體外細(xì)胞毒性實(shí)驗(yàn)，使用Bio-Radmodel-68酶標(biāo)儀在570nm波長下測(cè)定吸光度值，分析細(xì)胞活力；將HepG2細(xì)胞制成單細(xì)胞懸液使用光學(xué)顯微鏡觀察細(xì)胞態(tài)學(xué)變化；通過紫外可見光吸收光譜的方法進(jìn)行體外溶血分析。 （3）體內(nèi)動(dòng)物實(shí)驗(yàn)：隨機(jī)選取12只小鼠分為2組，一組注射Yb(OH)CO3為實(shí)驗(yàn)組，另一組注射生理鹽水為對(duì)照組。30天后將兩組小鼠進(jìn)行處死解剖進(jìn)行組織學(xué)分析來確定Yb(OH)CO3對(duì)小鼠的體內(nèi)毒性。 （4）計(jì)算機(jī)斷層攝影（CT）體外成像評(píng)價(jià)造影劑的效率：將不同濃度的納米粒子Yb(OH)CO3稀釋液和碘比醇稀釋液分別加入到含有瓊脂糖的PBS溶液中并使用飛利浦256層螺旋CT進(jìn)行掃描，結(jié)果以EP管所成CT值計(jì)算。 （5）體內(nèi)評(píng)價(jià)CT影像：使用飛利浦256層螺旋CT進(jìn)行掃描，通過多平面重組技術(shù)（MPR）將獲得的原始薄層軸位圖像建成所需要的冠狀位圖像。 （6）造影劑的體內(nèi)分布與代謝實(shí)驗(yàn)：將注射Yb(OH)CO3造影劑的小鼠在不同的時(shí)間點(diǎn)處死并提取主要器官以便定量分析鐿（Yb）粒子，使用ICP-MS分析從小鼠身上獲得的尿液和糞便提取樣品。 結(jié)果： （1）成功制備了納米粒子Yb(OH)CO3并對(duì)其進(jìn)行了形態(tài)和外貌的表征。從納米粒子Yb(OH)CO3的掃描電子顯微鏡(SEM)圖像中可以看到納米粒子樣品的表面光滑而且單個(gè)分散并呈大致相同的球形。 （2）MTT實(shí)驗(yàn)表明在有納米粒子存在的條件下培養(yǎng)48小時(shí)后仍然有91%以上的細(xì)胞能夠存活。體外細(xì)胞形態(tài)學(xué)觀察表面在有納米粒子存在的條件下細(xì)胞的正常生長并沒有受到影響。體外溶血分析實(shí)驗(yàn)表明在大劑量使用Yb(OH)CO3（1mg NPs/mL）的條件下幾乎沒有發(fā)生紅細(xì)胞的溶血現(xiàn)象。 （3）實(shí)驗(yàn)組和對(duì)照組中所有的小鼠均在飼養(yǎng)30天后均被處死并對(duì)其器官進(jìn)行提取，沒有觀察到納米粒子Yb(OH)CO3造成的組織損傷以及任何其他負(fù)性影響。 （4）Yb(OH)CO3組小鼠在不同時(shí)間點(diǎn)處死后發(fā)現(xiàn)鐿粒子主要聚集在網(wǎng)狀內(nèi)皮系統(tǒng)如肝臟和脾臟，其結(jié)果與CT影像一致。在注射造影劑1，3，5，7天后收集小鼠的尿液和糞便發(fā)現(xiàn)高濃度的鐿粒子。 （5）CT成像，隨著Yb(OH)CO3和碘比醇濃度的增加CT值逐漸升高，CT值與造影劑的濃度呈現(xiàn)良好的線性關(guān)系。但在相同濃度條件下Yb(OH)CO3的射線吸收計(jì)量明顯高于碘比醇的射線吸收計(jì)量。兩組小鼠肝臟和腎臟平掃CT值均無統(tǒng)計(jì)學(xué)差異。在注射造影劑30分鐘后，，Yb(OH)CO3組肝臟的CT值明顯高于碘比醇組，而Yb(OH)CO3組腎臟的CT值明顯低于碘比醇組具有顯著的統(tǒng)計(jì)學(xué)意義。注射造影劑3分鐘后碘比醇組的造影劑便大量聚集在腎臟，30分鐘后幾乎所有的造影劑都聚集于泌尿系統(tǒng)。時(shí)間延遲到2小時(shí)后Yb(OH)CO3組肝臟的CT值幾乎是碘比醇組的3倍，而腎臟CT值與平掃時(shí)相比幾乎沒有變化。 結(jié)論： （1）成功制備了低毒性、具有很好的組織相容性納米CT造影劑Yb(OH)CO3。 （2）Yb(OH)CO3體外CT成像、小鼠體內(nèi)CT成像以及對(duì)小鼠尿液和糞便的研究，初步明確了其與傳統(tǒng)造影劑碘比醇比較對(duì)組織影像的顯示有明顯的優(yōu)勢(shì)。
[Abstract]:Purpose :

A new type of nanometer CT angiography Yb ( OH ) CO3 was synthesized and its sample was characterized . The toxicity of Yb ( OH ) CO3 as CT contrast agent was studied , and the distribution and metabolism of the contrast agent in mice were studied .

Materials and Methods :

( 1 ) Preparation and characterization of nano - particle Yb ( OH ) CO3 : A homogeneous precipitation process based on urea was prepared by dissolving Yb ( NO3 ) 3 路 5H2O ( 7.5 mmol ) and urea ( 15 g ) in deionized water .

( 2 ) In vitro toxicity experiment : MTT assay was used for in vitro cytotoxicity test , and the absorbance value was measured at 570 nm using the Bio - Radmodel - 68 microplate reader , and the cell viability was analyzed ;
the HepG2 cells were made into a single cell suspension and the cell state change was observed by using an optical microscope ;
The in vitro hemolysis analysis was carried out by means of an ultraviolet visible light absorption spectrum .

( 3 ) In vivo animal experiment : 12 mice were randomly selected to be divided into 2 groups , one group was injected with Yb ( OH ) CO3 as the experimental group , and the other group received normal saline as the control group . After 30 days , two groups of mice were sacrificed and dissected to determine the toxicity of Yb ( OH ) CO3 to mice .

( 4 ) In vitro imaging of computed tomography ( CT ) : The efficiency of contrast agent was evaluated in vitro : different concentrations of nanoparticles Yb ( OH ) CO3 were added to PBS solution containing agarose and scanned by Philips 256 - layer spiral CT , and the results were calculated by the CT value of EP tube .

( 5 ) CT images were evaluated in vivo : 256 - slice spiral CT was used for scanning , and the obtained original thin - layer axial - bit image was built into the required coronal image by multi - plane reconstruction technique ( MPR ) .

( 6 ) In vivo distribution and metabolism experiment of contrast agent : mice injected with Yb ( OH ) CO3 contrast agent were sacrificed at different time points and the primary organs were extracted for quantitative analysis of ytterbium ( Yb ) particles , and urine and feces obtained from mice were analyzed using ICP - MS .

Results :

( 1 ) The nano - particle Yb ( OH ) CO3 was successfully prepared and characterized by morphology and appearance . The surface of the nano - particle sample can be seen to be smooth and spherical in the same spherical shape from the scanning electron microscope ( SEM ) image of the nano - particle Yb ( OH ) CO3 .

( 2 ) MTT assay showed that more than 91 % of the cells were able to survive in the presence of nanoparticles . The morphology of cells in vitro was not affected by the normal growth of cells in the presence of nanoparticles .

( 3 ) All the mice in the experimental group and the control group were sacrificed after 30 days of feeding and the organs were extracted , and no tissue damage caused by the nano - particle Yb ( OH ) CO3 and any other negative effects were observed .

( 4 ) Yb ( OH ) 3 group mice were sacrificed at different time points to find that ytterbium particles were mainly concentrated in reticuloendothelial system such as liver and spleen . The results were consistent with CT images . After 1 , 3 , 5 and 7 days injection of contrast agent , the urine and feces of mice were collected to find the high concentration ytterbium particles .

( 5 ) The CT value of Yb ( OH ) CO3 group was significantly higher than that of iodine - specific alcohol group . The CT value of Yb ( OH ) CO3 group was significantly higher than that of iodine - specific alcohol group . After 30 minutes of contrast agent , the CT value of the liver of Yb ( OH ) CO3 group was almost 3 times that of the group of iodine - specific alcohol , while the CT value of the kidney was almost unchanged compared with the time of plain scan .

Conclusion :

( 1 ) Low toxicity was successfully prepared , and a good tissue - compatible nano - CT contrast agent Yb ( OH ) CO3 was prepared .

( 2 ) In vitro CT imaging of Yb ( OH ) CO3 , CT imaging in mice and the study of urine and feces in mice , it is preliminarily clear that the comparison of iodine with traditional contrast agent has obvious advantages to the display of tissue images .
【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】：2014
【分類號(hào)】：R814

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本文編號(hào)：1996754