本文選題：高分子納米膠束 + 腎細(xì)胞癌��； 參考：《河北大學(xué)》2017年碩士論文

【摘要】：目的:1.構(gòu)建人離體腎臟腫瘤標(biāo)本灌注模型,將標(biāo)記有普羅碘銨的高分子納米膠束溶解于器官保存液中,進行人離體腎臟腫瘤標(biāo)本的循環(huán)灌注;2.進一步研究高分子納米膠束在離體腎癌標(biāo)本中的增強滲透保留效應(yīng)(EPR效應(yīng))及量化關(guān)系。方法:1.依據(jù)納入標(biāo)準(zhǔn)選擇符合要求的病例,與患者簽署知情同意書,術(shù)前與術(shù)者說明實驗要求,將離體腎癌標(biāo)本立即置管,并灌注器官保存液。2.置管后的腎臟腫瘤標(biāo)本先應(yīng)用GE Discovery HD750 CT進行一次掃描,再將腎臟連接灌注裝置,將溶有膠束的器官保存液持續(xù)灌注于腎臟,并應(yīng)用GE Discovery HD750 CT的GSI模式分別于灌注開始后1.0h、2.0h、3.0h、4.0h、5.0h、6.0h進行掃描;3.持續(xù)監(jiān)測灌注液PH值、腎臟產(chǎn)生尿量等指標(biāo),灌注結(jié)束后,將腎臟腫瘤標(biāo)本固定于10%甲醛液中,連同其余標(biāo)本送往病理科。4.實驗結(jié)束后利用GE ADW4.5工作站測量人腎臟腫瘤標(biāo)本內(nèi)高分子納米膠束的富集量,繪制圖表,利用SPSS19.0統(tǒng)計學(xué)軟件分析數(shù)據(jù)結(jié)果。結(jié)果:1.本實驗成功建立了人離體腎臟腫瘤標(biāo)本的體外循環(huán)灌注模型,16例腎臟腫瘤標(biāo)本均順利完成灌注,CT碘基圖膠束成像分布清晰,灌注過程中每只腎臟產(chǎn)生尿量平均40.05±5.22ml,灌注液PH值穩(wěn)定在7.35-7.45之間,灌注結(jié)束后病理顯示顯示腎臟正常組織細(xì)胞結(jié)構(gòu)存在,無明顯水腫壞死,細(xì)胞凋亡比例在灌注前后無明顯變化(P0.05);2.腫瘤區(qū)、正常腎臟皮質(zhì)區(qū)及髓質(zhì)區(qū)三個不同部位的碘含量,在灌注開始后各時間點與灌注前分別比較,結(jié)果顯示,腫瘤區(qū)碘含量在灌注前后的變化有統(tǒng)計學(xué)意義(p=0.00),在灌注開始后第1H即腫瘤區(qū)的碘含量即明顯升高(1.79±0.26)×100ug/cm3,且隨時間演變,表現(xiàn)出腫瘤部位碘含量的增高及蓄積,并能保持一定時間,逐漸升高至3H為最高峰,(2.19±0.36)×100ug/cm3。而正常腎皮質(zhì)和腎髓質(zhì)各個時間點的碘含量較灌注開始前均無明顯變化(p=1.00)。3.比較3種不同粒徑高分子納米膠束灌注腎臟腫瘤標(biāo)本,發(fā)現(xiàn)灌注后各組粒徑膠束在腫瘤區(qū)的碘含量、碘基曲線圖及峰值出現(xiàn)時間各不相同:A組在第4H時碘含量最高,為(2.41±0.21)×100ug/cm3,B組碘含量上升緩慢,但是碘含量持續(xù)升高時間較長,即保留時間較長;C組碘含量在灌注開始后上升快,到第2H即達(dá)頂峰,(2.34±0.17)×100ug/cm3,之后緩慢下降,不同粒徑膠束在腫瘤區(qū)的增強滲透保留作用各有特點,無明顯規(guī)律性。結(jié)論:1.人離體腎臟腫瘤標(biāo)本灌注試驗?zāi)Ｐ涂煽?灌注試驗不影響病理結(jié)果及腎臟生理功能,可獲得真實客觀的實驗結(jié)果,為腫瘤標(biāo)本的二次利用研究提供了新方法。2.通過載有普羅碘胺的高分子納米膠束進行離體腎臟腫瘤標(biāo)本的灌注實驗研究,并借助寶石能譜CT碘基圖技術(shù),可準(zhǔn)確獲得高分子納米膠束在腫瘤組織內(nèi)的富集量、動態(tài)演變規(guī)律及膠束含量的定量參數(shù)。3.高分子納米膠束在人離體腎細(xì)胞癌中存在EPR效應(yīng),且不同粒徑的高分子納米膠束在腫瘤內(nèi)的富集量、動態(tài)演變規(guī)律各有特點,提示腫瘤內(nèi)復(fù)雜的微循環(huán)結(jié)構(gòu)使得EPR效應(yīng)呈現(xiàn)多態(tài)性。
[Abstract]:Objective: 1. to construct the perfusion model of human renal tumor specimens, and to dissolve the macromolecule micelles labeled with proiodoniodide in the organ preservation solution and carry out the circulation perfusion of human renal tumor specimens. 2. further study the enhanced permeability retention effect (EPR effect) and quantitative relationship of the polymer nanomicelle in the isolated renal carcinoma. Method: 1. the cases were selected according to the inclusion criteria, and the informed consent was signed with the patients. Before and after the operation, the experimental requirements were given. The specimens of the renal carcinoma were immediately placed and the renal tumor specimens of the organ preservation solution.2. GE CT were first scanned with the Discovery HD750 CT, and then the renal connection perfusion device would be dissolved. GE Discovery HD750 CT GSI mode was applied to 1.0h, 1.0h, 2.0h, 3.0h, 4.0h, 5.0h, 6.0h were scanned after the perfusion of GSI, respectively. 3. continuous monitoring of the pH value of the perfusion solution, the urine volume of the kidney and so on. After the end of perfusion, the renal tumor specimens were fixed in the 10% formaldehyde solution and sent together with the rest specimens. After the.4. experiment in the pathology department, the concentration of polymer nanoscale micelles in human kidney tumor specimens was measured by GE ADW4.5 workstation. The chart was drawn and the results of the data were analyzed with SPSS19.0 statistics software. Results: 1. experiments successfully established an in vitro circulation model of human renal tumor specimens in vitro, and 16 specimens of renal tumor were finished successfully. The distribution of CT iodide micellar imaging was clear. The average urine output of each kidney in the process of perfusion was 40.05 + 5.22ml, and the pH value of the perfusion was stable between 7.35-7.45. The pathology showed that there was no obvious edema and necrosis in the normal tissue of the kidney after the end of perfusion. There was no obvious change in the proportion of apoptosis before and after perfusion (P0.05), and 2. swelling. The iodine content in three different parts of the tumor area, normal renal cortex and medullary area was compared with that before perfusion, and the results showed that the changes of iodine content before and after perfusion were statistically significant (p=0.00). The iodine content in the tumor area was significantly increased (1.79 + 0.26) x 100ug/cm3 after the beginning of perfusion. As time evolves, the iodine content of the tumor site is increased and accumulated, and it can maintain a certain time, gradually rising to the peak of 3H, (2.19 + 0.36) x 100ug/cm3. while the iodine content in the normal renal cortex and the renal medulla at each time point has no significant changes (p= 1).3. compared with 3 different particle sizes of polymer nano micelle perfusion The iodine content, iodine base curve and peak time of the micelles in the tumor area were different after perfusion. The iodine content of group A was the highest at 4H, which was (2.41 + 0.21) x 100ug/cm3, and the iodine content in group B increased slowly, but the iodine content continued to increase for a long time, that is, the retention time was longer, and the iodine content in C group was in perfusion. At the beginning, it rises quickly to the peak, reaching the peak, (2.34 + 0.17) x 100ug/cm3, and then slowly decreasing. The enhanced osmosis retention of the micelles of different particle sizes has its own characteristics, without obvious regularity. Conclusion: the perfusion test model of 1. human renal tumor specimens is reliable, and the perfusion test does not affect the pathological results and the kidney physiological function. The actual and objective experimental results provide a new method for the two use of tumor specimens. The experimental study on the perfusion of renal tumor specimens in vitro by high polymer nanomicelles containing proiodonamide is carried out by.2., and the concentration of the polymer nanomicelles in the tumor tissues can be accurately obtained by means of the gemstone CT iodide basis. .3. polymer nanomicelles have the EPR effect in human renal cell carcinoma, and the dynamic evolution of the polymer nanomicelles with different particle sizes in the tumor, suggesting that the complex microcirculation structure in the tumor makes the EPR effect polymorphic.
【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.11

【參考文獻】

相關(guān)期刊論文 前7條

1 郭放;鄭振東;謝曉冬;;晚期腎癌分子靶向治療新進展[J];中國腫瘤臨床;2016年22期

2 曾憲鵬;葉U_發(fā);王彥峰;李玲;熊艷;鐘自彪;范曉禮;劉忠忠;李寧;;低溫機械灌注與冷保存應(yīng)用于心臟死亡器官捐贈供腎效果的薈萃分析[J];中華器官移植雜志;2015年04期

3 李勁草;孫嵐;姜爽;劉巖;姚紅娟;蒲韻竹;朱靜雨;張英鴿;;納米藥物釋放系統(tǒng)在腫瘤組織中增強的透過與滯留效應(yīng)及其影響因素[J];中國藥理學(xué)與毒理學(xué)雜志;2015年01期

4 胡笑梅;黃渝然;薛雪;趙元元;莊小溪;梁興杰;楊靜玉;;基于腫瘤異常結(jié)構(gòu)的納米藥物設(shè)計[J];生物化學(xué)與生物物理進展;2013年10期

5 張志強;于德新;江山;施浩強;阮厚鑫;褚晗;;腎細(xì)胞癌卵巢及腎上腺轉(zhuǎn)移一例報告[J];中華泌尿外科雜志;2012年09期

6 孫飛達(dá);王東文;米振國;;腎癌分子靶向治療的現(xiàn)狀及研究進展[J];現(xiàn)代泌尿生殖腫瘤雜志;2012年01期

7 黃紅娜;張丹參;張力;丁杰;;納米藥物載體系統(tǒng)的研究[J];河北北方學(xué)院學(xué)報(醫(yī)學(xué)版);2010年02期

，

本文編號：1911317