高分子纳米胶束在离体肾癌标本中EPR效应的研究

发布时间：2018-05-19 19:19

本文选题：高分子纳米胶束 + 肾细胞癌　；参考：《河北大学》2017年硕士论文

【摘要】：目的:1.构建人离体肾脏肿瘤标本灌注模型,将标记有普罗碘铵的高分子纳米胶束溶解于器官保存液中,进行人离体肾脏肿瘤标本的循环灌注;2.进一步研究高分子纳米胶束在离体肾癌标本中的增强渗透保留效应(EPR效应)及量化关系。方法:1.依据纳入标准选择符合要求的病例,与患者签署知情同意书,术前与术者说明实验要求,将离体肾癌标本立即置管,并灌注器官保存液。2.置管后的肾脏肿瘤标本先应用GE Discovery HD750 CT进行一次扫描,再将肾脏连接灌注装置,将溶有胶束的器官保存液持续灌注于肾脏,并应用GE Discovery HD750 CT的GSI模式分别于灌注开始后1.0h、2.0h、3.0h、4.0h、5.0h、6.0h进行扫描;3.持续监测灌注液PH值、肾脏产生尿量等指标,灌注结束后,将肾脏肿瘤标本固定于10%甲醛液中,连同其余标本送往病理科。4.实验结束后利用GE ADW4.5工作站测量人肾脏肿瘤标本内高分子纳米胶束的富集量,绘制图表,利用SPSS19.0统计学软件分析数据结果。结果:1.本实验成功建立了人离体肾脏肿瘤标本的体外循环灌注模型,16例肾脏肿瘤标本均顺利完成灌注,CT碘基图胶束成像分布清晰,灌注过程中每只肾脏产生尿量平均40.05±5.22ml,灌注液PH值稳定在7.35-7.45之间,灌注结束后病理显示显示肾脏正常组织细胞结构存在,无明显水肿坏死,细胞凋亡比例在灌注前后无明显变化(P0.05);2.肿瘤区、正常肾脏皮质区及髓质区三个不同部位的碘含量,在灌注开始后各时间点与灌注前分别比较,结果显示,肿瘤区碘含量在灌注前后的变化有统计学意义(p=0.00),在灌注开始后第1H即肿瘤区的碘含量即明显升高(1.79±0.26)×100ug/cm3,且随时间演变,表现出肿瘤部位碘含量的增高及蓄积,并能保持一定时间,逐渐升高至3H为最高峰,(2.19±0.36)×100ug/cm3。而正常肾皮质和肾髓质各个时间点的碘含量较灌注开始前均无明显变化(p=1.00)。3.比较3种不同粒径高分子纳米胶束灌注肾脏肿瘤标本,发现灌注后各组粒径胶束在肿瘤区的碘含量、碘基曲线图及峰值出现时间各不相同:A组在第4H时碘含量最高,为(2.41±0.21)×100ug/cm3,B组碘含量上升缓慢,但是碘含量持续升高时间较长,即保留时间较长;C组碘含量在灌注开始后上升快,到第2H即达顶峰,(2.34±0.17)×100ug/cm3,之后缓慢下降,不同粒径胶束在肿瘤区的增强渗透保留作用各有特点,无明显规律性。结论:1.人离体肾脏肿瘤标本灌注试验模型可靠,灌注试验不影响病理结果及肾脏生理功能,可获得真实客观的实验结果,为肿瘤标本的二次利用研究提供了新方法。2.通过载有普罗碘胺的高分子纳米胶束进行离体肾脏肿瘤标本的灌注实验研究,并借助宝石能谱CT碘基图技术,可准确获得高分子纳米胶束在肿瘤组织内的富集量、动态演变规律及胶束含量的定量参数。3.高分子纳米胶束在人离体肾细胞癌中存在EPR效应,且不同粒径的高分子纳米胶束在肿瘤内的富集量、动态演变规律各有特点,提示肿瘤内复杂的微循环结构使得EPR效应呈现多态性。
[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.
【学位授予单位】：河北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.11

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