非酒精性脂肪肝炎枯否细胞MR成像的实验研究
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摘要
本研究以大鼠为研究对象,在建立非酒精性脂肪肝炎(NASH)的动物模型基础上,采用自行研制的壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4作为磁共振成像的对比剂,经大鼠尾静脉注射CS-g-PAA/ Fe_3O_4后行1.5T MR增强扫描来初步评估大鼠NASH枯否细胞(KC)的吞噬功能。共分为三个部分。
第一部分:壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4的制备
目的:用壳聚糖-g-聚丙烯酸(CS-g-PAA)对纳米Fe_3O_4进行表面改性,使其在中性溶液中仍具备水分散稳定性能和超顺磁性。
方法:采用接枝聚合的方法制备了壳聚糖-g-聚丙烯酸(CS-g-PAA)表面改性Fe_3O_4并得到其水分散稳定体系。用傅立叶红外光谱仪(FTIR)表征了复合纳米粒子的结构,扫描式电子显微镜(SEM)、投射电子显微镜(TEM)表征了复合纳米粒子的尺寸与形貌,X射线衍射(XRD)、振荡样品磁强计(VSM)分别表征了复合纳米粒子的晶型结构与超顺磁性。并研究了表面改性与聚合物层的组成对Fe_3O_4在水体系中的分散稳定性的影响,动态光散射(DLS)表征了复合粒子的水力半径,表明粒子的水力半径随体系PH值的变化而变化。
结果:用壳聚糖及聚丙烯酸表面修饰可以成功地获得Fe_3O_4纳米粒子的中性(PH=7.4)水悬浮分散胶体。CS-g-PAA包裹后的Fe_3O_4粒子直径在15.0-60.0nm之间呈现稳定的单体分散状态,单个粒子呈现球形或椭圆形,纳米粒子的粒径分布均匀,并且其晶体结构没有改变,具有稳定的超顺磁性。
结论:通过CS-g-PAA表面改性的Fe_3O_4纳米粒子,在中性环境下具备水分散稳定性能。CS-g-PAA/Fe_3O_4粒子粒径分布在15.0-60.0nm之间,具有与Fe_3O_4类似的尖晶石结构,超顺磁性稍有降低,但仍可以满足磁共振对比剂的要求。
第二部分:壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4磁共振体外信号检测
目的:研究磁共振检测壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4(PH=7.4)的稳定性及其在不同浓度下体外磁共振信号的变化规律。
方法:将CS-g-PAA/Fe_3O_4磷酸盐溶液按浓度梯度排列,MRI检测其稳定性及其信号变化;所用MRI序列为:FSE T1WI、FRFSE T2WI及FIESTA T2*WI。
结果:CS-g-PAA/Fe_3O_4在PH=7.4时MRI各序列信号均匀(P>0.05);CS-g-PAA/Fe_3O_4在T1WI上信号强度随铁质量浓度的增加先升高后降低,在T2WI及T2*WI上随质量浓度的增加信号降低;浓度越低,T1WI及T2*WI较T2WI越敏感,以T2*WI最敏感(P<0.05);在浓度≤20mg/L时,各序列上信号变化均较明显。
结论:临床应用型1.5T MRI可检测CS-g-PAA/Fe_3O_4的稳定性;在浓度≤20mg/L时MRI信号改变明显;最敏感MR检测序列为T2*WI。
第三部分:壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4磁共振成像评估大鼠非酒精性脂肪肝炎枯否细胞功能的实验研究
目的:初步探讨CS-g-PAA/Fe_3O_4作为MRI对比剂评估大鼠非酒精性脂肪肝炎(NASH)枯否细胞(KC)功能的可行性。
方法:20只雄性SD大鼠按完全随机法分为实验组和对照组,每组10只,实验组喂养高脂饲料,对照组喂养普通饲料。8周后对所有大鼠行肝脏MRI及CS-g-PAA/Fe_3O_4增强扫描,计算肝脏组织平均信号强度下降百分比(PSIL)和CS-g-PAA/Fe_3O_4增强前后肝脾对比信号强度比值(RSIR),测定血清总胆固醇(TC)和甘油三酯(TG)值,并取肝脏标本行HE染色和普鲁士蓝染色分析病理表现。
结果:实验组1只大鼠因麻醉过深死亡,其余9只血清TC及TG值分别为(6.58±1.25) mmol/L和(1.53±0.23) mmol/L ,较对照组[(1.64±0.22) mmol/L和(0.55±0.14) mmol/L]均明显升高(t值分别为11.716和11.558,P值均<0.01)。CS-g-PAA/Fe_3O_4增强扫描后两组肝实质信号强度在各序列明显下降,在PDWI及T1WI上实验组下降程度分别为(34.78±4.51)%和(60.38±3.49%),较对照组[分别为(64.96±2.42)%和(81.08±1.66)% ]小,差异有统计学意义(t值分别为-18.415和-16.240,P值均<0.01)。PDWI、T2WI、T2*WI和T1WI序列实验组CS-g-PAA/Fe_3O_4增强前后肝脾RSIR分别为(1.002±0.141、5.000±0.516、20.004±1.490和2.601±0.077,较对照组(0.400±0.102、1.500±0.115、-0.3±0.058和0.503±0.105)大(t值分别为10.745、19.800、39.168和92.785,P值均<0.01);实验组肝脏组织中普鲁士蓝染色阳性颗粒积分(2.33±0.50)分较对照组(4分)明显减少(t=-10.000,P<0.01)。
结论:高脂饮食诱导的SD大鼠NASH模型接近人类发病情况且容易建立,临床应用型1.5T MRI通过CS-g-PAA/Fe_3O_4增强肝脏扫描可评估KC细胞的功能,提示NASH的发病机制与KC功能的下降有关。
This study used self-developed the Fe_3O_4 nanoparticles modified with chitosan-graft-poly (acryl acid) (CS-g-PAA) as a magnetic resonance imaging contrast agent, taking rat as experimental materials, to establish the animal model of non-alcoholic steatohepatitis (NASH) , to perform liver 1.5T MRI, were imaged before and after CS-g-PAA / Fe_3O_4 nanoparticles from the tail vein infusion, assessing rat NASH Kupffer cells (KC) phagocytic function, Which was divided into three parts.
Part I: The preparation of Fe_3O_4 nanoparticles modified with chitosan-graft-poly (acryl acid) (CS-g-PAA)
Objective: The well-dispersed Fe_3O_4 nanoparticles suspension was successfully prepared through surface modification with chitosan–poly (acrylic acid) (CS–PAA) copolymer by graft copolymerization technique.
Methods: The graft polymerization was prepared by Chitosan–poly (acrylic acid) (CS–PAA) surface modification of Fe_3O_4 and get their water dispersed stable system. The structure of synthesized nanoparticles was characterized by Fourier transform infrared spectrometer (FTIR). The size and morphology of the nanoparticles was investigated by field emission scanning electron microscopy (FE-SEM) and Transmission electron microscope (TEM). The crystallization and superparamagnetism of the nanoparticles were characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) respectively. The hydrodynamic radius of the modified particles was characterized by Dynamic light scattering (DLS). The results indicated that the hydrodynamic radius was dependant on PH of the system.
Results:The Fe_3O_4 nanoparticles successfully modified with chitosan-g-polyacrylic acid (CS-g-PAA). CS-g-PAA/Fe_3O_4 nanoparticles were in water (PH=7.4)dispersion stability on globose or ellipse, diameter 15-60nm, uniform size distribution, and its crystal structure has not changed, with the stability of superparamagnetism.
Conclusions: The well-dispersed Fe_3O_4 nanoparticle suspension was successfully prepared on PH=7.4 through surface modification with Chitosan–poly (acrylic acid) (CS–PAA) copolymer, the stability of its suspension mechanism is electrostatic repulsion and steric effects of synergy. CS-g-PAA/Fe_3O_4 nanoparticle size distribution of the 15.0-60.0nm, Which has the spinel structure, superparamagnetism slightly lower, but still meet the requirements of MRI contrast agent.
Part II: MR imaging of CS-g-PAA/Fe_3O_4 nanoparticles in vitro
Objective: To study the stability and the changing patterns of MR signals in differrnt concentration of CS-g-PAA/Fe_3O_4 nanoparticles (PH=7.4) in vitro magnetic resonance imaging.
Methods: The CS-g-PAA/Fe_3O_4 nanoparticles phosphate solution were disposed by density, to observe the stability of CS-g-PAA/Fe_3O_4 and regular of MR signal; MR imaging was performed as following sequences: FSE T1WI, FRFSE T2WI and FIESTA T2*WI.
Results: The CS-g-PAA/Fe_3O_4 nanoparticles were homogeneous MR signal (P>0.05). The signal intensity of CS-g-PAA/Fe_3O_4 nanoparticles on T1WI was firstly increased, but decreased following the increase of the concentration of Fe_3O_4. The signal on T2WI and T2*WI decreased as the increase of the concentration of Fe_3O_4. The lower the concentration, the more sensitive on T1WI and T2*WI when compared with that of T2WI, with T2*WI the most significant (P<0.05). The changes of signal intensity in all sequences were more distinct as the iron concentration≤20mg/l.
Conclusion: The stability of CS-g-PAA/Fe_3O_4 nanoparticles could be examined by 1.5T MR scan using in clinical practice, the changes of signal intensity were remarked when iron concentrations≤20mg/l. T2*WI was the most sensitive sequence for detecting the CS-g-PAA/Fe_3O_4 nanoparticles in vitro.
Part III: A preliminary study on the phagocytic activity of Kupffer cells with CS-g-PAA/Fe_3O_4 nanoparticles enhanced MR imaging in a rat nonalcoholic steatohepatitis model
Objective: To investigate the feasibility of using CS-g-PAA/Fe_3O_4 nanoparticles as MRI contrast agent to assess rat nonalcoholic steatohepatitis Kupffer cells (KC) function.
Methods: Twenty male SD rats were randomly divided into experimental and control group, 10 rats in each group, experimental group was fed high fat diet, control group fed normal diet. After eight weeks, plain MR and CS-g-PAA/Fe_3O_4 enhanced were performed in all the rats; Blood lipids were measured, and HE and Perl’s blue staining in all livers specimen was done. The related result of the staining were analyzed.
Results: Experimental group TC and TG levels [(6.58±1.25) mmol/L and (1.53±0.23) mmol/L respectively] were significantly higher than control group [(1.64±0.22) mmol/L and (0.55±0.14) mmol/L respectively] (t = 11.716 and 11.558, P <0. 01); Experimental and control group hepatic signal intensity decreased in all sequences after CS-g-PAA/Fe_3O_4 enhanced, but in experimental group the level of decline [(34.78±4.51)% and (60.38±3.49%) respectively] was less than control group [(64.96±2.42)% and (81.08±1.66)% respectively] on PDWI and T1WI, and statistically significant difference (t = -18.415 and -16.240, P <0.01) were found. In experimental group the ratio of signal intensity of liver to spleen(1.002±0.141, 5.000±0.516, 20.004±1.490 and 2.601±0.077)was more than control group(0.400±0.102, 1.500±0.115, -0.3±0.058 and 0.503±0.105)before and after contrast enhancement on PDWI, T2WI, T2*WI and T1WI (t = 10.745, 19.800, 39.168 and 92.785, P <0.01). Typical histological hepatic lesions of NASH were observed in experimental group. Perl's staining-positive particles in experimental group(2.33±0.50)were fewer than in control group (4) (t= -10.000, P <0.01).
Conclusion: The high-fat diet-induced model of SD rats close to the human NASH and was easy to establish. Clinical application of CS-g-PAA/Fe_3O_4 enhanced MR successfully assessed the phagocytic activity of Kupffer cells in the study, and it suggested that the pathogenesis of NASH related to the decreased phagocytic activity of Kupffer cells.
第一部分:壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4的制备
目的:用壳聚糖-g-聚丙烯酸(CS-g-PAA)对纳米Fe_3O_4进行表面改性,使其在中性溶液中仍具备水分散稳定性能和超顺磁性。
方法:采用接枝聚合的方法制备了壳聚糖-g-聚丙烯酸(CS-g-PAA)表面改性Fe_3O_4并得到其水分散稳定体系。用傅立叶红外光谱仪(FTIR)表征了复合纳米粒子的结构,扫描式电子显微镜(SEM)、投射电子显微镜(TEM)表征了复合纳米粒子的尺寸与形貌,X射线衍射(XRD)、振荡样品磁强计(VSM)分别表征了复合纳米粒子的晶型结构与超顺磁性。并研究了表面改性与聚合物层的组成对Fe_3O_4在水体系中的分散稳定性的影响,动态光散射(DLS)表征了复合粒子的水力半径,表明粒子的水力半径随体系PH值的变化而变化。
结果:用壳聚糖及聚丙烯酸表面修饰可以成功地获得Fe_3O_4纳米粒子的中性(PH=7.4)水悬浮分散胶体。CS-g-PAA包裹后的Fe_3O_4粒子直径在15.0-60.0nm之间呈现稳定的单体分散状态,单个粒子呈现球形或椭圆形,纳米粒子的粒径分布均匀,并且其晶体结构没有改变,具有稳定的超顺磁性。
结论:通过CS-g-PAA表面改性的Fe_3O_4纳米粒子,在中性环境下具备水分散稳定性能。CS-g-PAA/Fe_3O_4粒子粒径分布在15.0-60.0nm之间,具有与Fe_3O_4类似的尖晶石结构,超顺磁性稍有降低,但仍可以满足磁共振对比剂的要求。
第二部分:壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4磁共振体外信号检测
目的:研究磁共振检测壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4(PH=7.4)的稳定性及其在不同浓度下体外磁共振信号的变化规律。
方法:将CS-g-PAA/Fe_3O_4磷酸盐溶液按浓度梯度排列,MRI检测其稳定性及其信号变化;所用MRI序列为:FSE T1WI、FRFSE T2WI及FIESTA T2*WI。
结果:CS-g-PAA/Fe_3O_4在PH=7.4时MRI各序列信号均匀(P>0.05);CS-g-PAA/Fe_3O_4在T1WI上信号强度随铁质量浓度的增加先升高后降低,在T2WI及T2*WI上随质量浓度的增加信号降低;浓度越低,T1WI及T2*WI较T2WI越敏感,以T2*WI最敏感(P<0.05);在浓度≤20mg/L时,各序列上信号变化均较明显。
结论:临床应用型1.5T MRI可检测CS-g-PAA/Fe_3O_4的稳定性;在浓度≤20mg/L时MRI信号改变明显;最敏感MR检测序列为T2*WI。
第三部分:壳聚糖-g-聚丙烯酸(CS-g-PAA)纳米Fe_3O_4磁共振成像评估大鼠非酒精性脂肪肝炎枯否细胞功能的实验研究
目的:初步探讨CS-g-PAA/Fe_3O_4作为MRI对比剂评估大鼠非酒精性脂肪肝炎(NASH)枯否细胞(KC)功能的可行性。
方法:20只雄性SD大鼠按完全随机法分为实验组和对照组,每组10只,实验组喂养高脂饲料,对照组喂养普通饲料。8周后对所有大鼠行肝脏MRI及CS-g-PAA/Fe_3O_4增强扫描,计算肝脏组织平均信号强度下降百分比(PSIL)和CS-g-PAA/Fe_3O_4增强前后肝脾对比信号强度比值(RSIR),测定血清总胆固醇(TC)和甘油三酯(TG)值,并取肝脏标本行HE染色和普鲁士蓝染色分析病理表现。
结果:实验组1只大鼠因麻醉过深死亡,其余9只血清TC及TG值分别为(6.58±1.25) mmol/L和(1.53±0.23) mmol/L ,较对照组[(1.64±0.22) mmol/L和(0.55±0.14) mmol/L]均明显升高(t值分别为11.716和11.558,P值均<0.01)。CS-g-PAA/Fe_3O_4增强扫描后两组肝实质信号强度在各序列明显下降,在PDWI及T1WI上实验组下降程度分别为(34.78±4.51)%和(60.38±3.49%),较对照组[分别为(64.96±2.42)%和(81.08±1.66)% ]小,差异有统计学意义(t值分别为-18.415和-16.240,P值均<0.01)。PDWI、T2WI、T2*WI和T1WI序列实验组CS-g-PAA/Fe_3O_4增强前后肝脾RSIR分别为(1.002±0.141、5.000±0.516、20.004±1.490和2.601±0.077,较对照组(0.400±0.102、1.500±0.115、-0.3±0.058和0.503±0.105)大(t值分别为10.745、19.800、39.168和92.785,P值均<0.01);实验组肝脏组织中普鲁士蓝染色阳性颗粒积分(2.33±0.50)分较对照组(4分)明显减少(t=-10.000,P<0.01)。
结论:高脂饮食诱导的SD大鼠NASH模型接近人类发病情况且容易建立,临床应用型1.5T MRI通过CS-g-PAA/Fe_3O_4增强肝脏扫描可评估KC细胞的功能,提示NASH的发病机制与KC功能的下降有关。
This study used self-developed the Fe_3O_4 nanoparticles modified with chitosan-graft-poly (acryl acid) (CS-g-PAA) as a magnetic resonance imaging contrast agent, taking rat as experimental materials, to establish the animal model of non-alcoholic steatohepatitis (NASH) , to perform liver 1.5T MRI, were imaged before and after CS-g-PAA / Fe_3O_4 nanoparticles from the tail vein infusion, assessing rat NASH Kupffer cells (KC) phagocytic function, Which was divided into three parts.
Part I: The preparation of Fe_3O_4 nanoparticles modified with chitosan-graft-poly (acryl acid) (CS-g-PAA)
Objective: The well-dispersed Fe_3O_4 nanoparticles suspension was successfully prepared through surface modification with chitosan–poly (acrylic acid) (CS–PAA) copolymer by graft copolymerization technique.
Methods: The graft polymerization was prepared by Chitosan–poly (acrylic acid) (CS–PAA) surface modification of Fe_3O_4 and get their water dispersed stable system. The structure of synthesized nanoparticles was characterized by Fourier transform infrared spectrometer (FTIR). The size and morphology of the nanoparticles was investigated by field emission scanning electron microscopy (FE-SEM) and Transmission electron microscope (TEM). The crystallization and superparamagnetism of the nanoparticles were characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) respectively. The hydrodynamic radius of the modified particles was characterized by Dynamic light scattering (DLS). The results indicated that the hydrodynamic radius was dependant on PH of the system.
Results:The Fe_3O_4 nanoparticles successfully modified with chitosan-g-polyacrylic acid (CS-g-PAA). CS-g-PAA/Fe_3O_4 nanoparticles were in water (PH=7.4)dispersion stability on globose or ellipse, diameter 15-60nm, uniform size distribution, and its crystal structure has not changed, with the stability of superparamagnetism.
Conclusions: The well-dispersed Fe_3O_4 nanoparticle suspension was successfully prepared on PH=7.4 through surface modification with Chitosan–poly (acrylic acid) (CS–PAA) copolymer, the stability of its suspension mechanism is electrostatic repulsion and steric effects of synergy. CS-g-PAA/Fe_3O_4 nanoparticle size distribution of the 15.0-60.0nm, Which has the spinel structure, superparamagnetism slightly lower, but still meet the requirements of MRI contrast agent.
Part II: MR imaging of CS-g-PAA/Fe_3O_4 nanoparticles in vitro
Objective: To study the stability and the changing patterns of MR signals in differrnt concentration of CS-g-PAA/Fe_3O_4 nanoparticles (PH=7.4) in vitro magnetic resonance imaging.
Methods: The CS-g-PAA/Fe_3O_4 nanoparticles phosphate solution were disposed by density, to observe the stability of CS-g-PAA/Fe_3O_4 and regular of MR signal; MR imaging was performed as following sequences: FSE T1WI, FRFSE T2WI and FIESTA T2*WI.
Results: The CS-g-PAA/Fe_3O_4 nanoparticles were homogeneous MR signal (P>0.05). The signal intensity of CS-g-PAA/Fe_3O_4 nanoparticles on T1WI was firstly increased, but decreased following the increase of the concentration of Fe_3O_4. The signal on T2WI and T2*WI decreased as the increase of the concentration of Fe_3O_4. The lower the concentration, the more sensitive on T1WI and T2*WI when compared with that of T2WI, with T2*WI the most significant (P<0.05). The changes of signal intensity in all sequences were more distinct as the iron concentration≤20mg/l.
Conclusion: The stability of CS-g-PAA/Fe_3O_4 nanoparticles could be examined by 1.5T MR scan using in clinical practice, the changes of signal intensity were remarked when iron concentrations≤20mg/l. T2*WI was the most sensitive sequence for detecting the CS-g-PAA/Fe_3O_4 nanoparticles in vitro.
Part III: A preliminary study on the phagocytic activity of Kupffer cells with CS-g-PAA/Fe_3O_4 nanoparticles enhanced MR imaging in a rat nonalcoholic steatohepatitis model
Objective: To investigate the feasibility of using CS-g-PAA/Fe_3O_4 nanoparticles as MRI contrast agent to assess rat nonalcoholic steatohepatitis Kupffer cells (KC) function.
Methods: Twenty male SD rats were randomly divided into experimental and control group, 10 rats in each group, experimental group was fed high fat diet, control group fed normal diet. After eight weeks, plain MR and CS-g-PAA/Fe_3O_4 enhanced were performed in all the rats; Blood lipids were measured, and HE and Perl’s blue staining in all livers specimen was done. The related result of the staining were analyzed.
Results: Experimental group TC and TG levels [(6.58±1.25) mmol/L and (1.53±0.23) mmol/L respectively] were significantly higher than control group [(1.64±0.22) mmol/L and (0.55±0.14) mmol/L respectively] (t = 11.716 and 11.558, P <0. 01); Experimental and control group hepatic signal intensity decreased in all sequences after CS-g-PAA/Fe_3O_4 enhanced, but in experimental group the level of decline [(34.78±4.51)% and (60.38±3.49%) respectively] was less than control group [(64.96±2.42)% and (81.08±1.66)% respectively] on PDWI and T1WI, and statistically significant difference (t = -18.415 and -16.240, P <0.01) were found. In experimental group the ratio of signal intensity of liver to spleen(1.002±0.141, 5.000±0.516, 20.004±1.490 and 2.601±0.077)was more than control group(0.400±0.102, 1.500±0.115, -0.3±0.058 and 0.503±0.105)before and after contrast enhancement on PDWI, T2WI, T2*WI and T1WI (t = 10.745, 19.800, 39.168 and 92.785, P <0.01). Typical histological hepatic lesions of NASH were observed in experimental group. Perl's staining-positive particles in experimental group(2.33±0.50)were fewer than in control group (4) (t= -10.000, P <0.01).
Conclusion: The high-fat diet-induced model of SD rats close to the human NASH and was easy to establish. Clinical application of CS-g-PAA/Fe_3O_4 enhanced MR successfully assessed the phagocytic activity of Kupffer cells in the study, and it suggested that the pathogenesis of NASH related to the decreased phagocytic activity of Kupffer cells.
引文
[1] Paschos P, Paletas K. Non alcoholic fatty liver disease and metabolic syndrome. Hippokratia, 2009, 3: 9-19.
[2] Greenfield V, Cheung O, Sanyal AJ. Recent advances in nonalcholic fatty liver disease. Curr Opin Gastroenterol, 2008, 24: 320-327.
[3] Polyzos SA, Kountouras J, Zavos C. Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med, 2009, 9:299-314.
[4] Kashi MR, Torres DM, Harrison SA. Current and emerging therapies in nonalcoholic fatty liver disease. Semin Liver Dis, 2008, 28: 396-406.
[5]孟二红,赵景民.非酒精性脂肪性肝炎的研究进展[J].世界华人消化杂志, 2002, 10:1206-1209.
[6] Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology, 1998, 114: 842-845.
[7]成军,李莉,张玲霞,等.丙型肝炎病毒感染与脂类代谢的相关性.肝脏, 2002, 7: 56-58.
[8] Tomita K, Tamiya G, Ando S, Ohsumi K, Chiyo T, Mizutani A, Kitamura N, Toda K, Kaneko T, Horie Y, Han JY, Kato S, Shimoda M, Oike Y, Tomizawa M, Makino S, Ohkura T, Saito H, Kumagai N, Nagata H, Ishii H, Hibi T. Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice. Gut, 2006, 55: 415-424.
[9] Shimada M, Hashimoto E, Taniai M, et al. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis[J]. Hepatol, 2002, 37(1): 154-160.
[10] Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology, 2002, 123(1): 134-140.
[11] Tsujimoto T, Kawaratani H, Kitazawa T, et al. Decreased phagocytic activity ofKupffer cells in a rat nonalcoholic steatohepatitis model. World J Gastroenterol, 2008, 14(39):6036-6043.
[12] Iijima H, Moriyasu F, Tsuchiya K, et al. Decrease in accumulation of ultrasound contrast microbubbles in non-alcoholic steatohepatitis. Hepatol Res, 2007, 37(9): 722-730.
[13] Okuhata Y. Delivery of diagnostic agents for magnetic resonance imaging.Adv Drug Deliv Rev, 1999, 37(1-3):121-137.
[14]杨华,张小明,邵阳,等.超顺性氧化铁在细胞内外对磁共振信号的影响.中国组织工程研究与临床康复, 2008, 12(30):5869-5872.
[15]赵朝辉,姚素薇,张卫国.纳米Fe_3O_4磁性颗粒的制备及应用现状[J].化工进展, 2005, 24: 865-868.
[1] Bowman K, Leong KW. Chitosan nanoparticlos for oral drug and gene delivery[J].IntJ Nanomedicine. 2006,l(2):117-128.
[2] Chertok B, Moffat BA, David AE, et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials, 2008, 29(4): 487–496.
[3] Park K,Kim JH,Nam YS,et a1.Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles[J].J Control Release,2007,122(3): 305-314.
[4]赵朝辉,姚素薇,张卫国.纳米Fe_3O_4磁性颗粒的制备及应用现状[J].化工进展, 2005, 24(8): 865-868.
[5]安江红,敖绪军,钱莘,等.壳聚糖纳米颗粒作为基因载体的初步研究.医学研究生学报,2008,21(8):790-794.
[6] Sobn BH, Cohen RE,Papaefthymiou GC, Magnetic properties of iron oxide nanoclusters within microdomains of block copolymers[J] . J Magn Magn Mater, 1998, 182: 216-224.
[7] Chertok B, Moffat BA, David AE, et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials, 2008, 29: 487-496.
[8]麦筱莉,滕皋军,马占龙,等.纳米磁粒子复合物标记对内皮祖细胞生物学特性影响的实验研究.中华放射学杂志, 2008, 42: 758-764.
[9]揭少卫,杨黎明,等.原位聚合法制备壳聚糖/聚丙烯酸水凝胶磁微球及其性能表征.高校化学工程学报, 2008, 22: 850-854.
[1] Lauffer RB. Magnetic resonance contrast media:principle and progress. Magn Reson Q, 1990, 6(2):65-84.
[2] Kim MJ, Kim JH, Choi JY, et al. Optimal TE for SPIO enhanced gradient recalled echo MRI for the detection of focal hepatic lesion. AJR Am J Roentgenol, 2006, 187(3): 255-266.
[3] Taupitz M, Schmitz S, Hamm B. Superparamagnetic iron oxide particles: current state and future development, Rofo 2003, 175(6): 752-765.
[4]景猛,刘新权,刘恩重.神经干细胞超顺磁性氧化铁纳米粒子标记和体内MRI示踪[J].中华神经外科疾病研究杂志, 2006,5(1):92-93.
[5] Tanimoto A, Mukai M, Kuribayashi S. Evaluation of superparamagnetic iron oxide for MR imaging of liver injury: proton relaxation mechanisms and optimal MR imaging parameter. Magn Reson Med Sci, 2006, 5(2):89-98.
[6]揭少卫,杨黎明,等.原位聚合法制备壳聚糖/聚丙烯酸水凝胶磁微球及其性能表征.高校化学工程学报, 2008, 22(5): 850-854.
[7] Chenga FY, Sua CH, Yanga TS, et al. Charecterization of aqueous dispersions of Fe_3O_4 nanoparticles and their biomedical applications. Biomaterials, 2005, 26(7): 729-738.
[8]许海燕.纳米技术在医学领域的应用研究.中华医学杂志, 2006, 86(8): 505-506.
[9]麦筱莉,滕皋军,马占龙,等.纳米磁粒子复合物标记对内皮祖细胞生物学特性影响的实验研究.中华放射学杂志, 2008, 42(7): 758—764.
[10] Frank JA,Miller BR,Arbab AS, et al. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology,2003, 228(2): 480-487.
[11]汪源浩,隋卫平,王恩峰.壳聚糖的化学改性及应用研究进展[J].济南大学学报,2007, 21(2): 140-144
[12]刘慧,壳聚糖微球/纳米粒的制备及其性能研究.浙江大学硕士学位论文,2007
[13] Okuhata Y.Delivery of diagnostic agcnts for magnetic resonance imaging.Adv Drug Deliv Rev, 1999, 37(1-3): 12l-137. [14]杨华,张小明,邵阳,等.超顺性氧化铁在细胞内外对磁共振信号的影响.中国组织工程研究与临床康复, 2008, 12(30): 5869-5872. [15] Simon GH, Bauer J, Sabomvski O, et a1. T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5 T and 3T clinical MR scanning.Eur Radiol, 2006, 16(3): 738-745. [16] Daldrup.Link HE,Rudelius M,Oostendorp RA,et a1.Targeting of hematopoietic progenitor cells with MR contrast agents.Radiology 2003,228(3):760-767. [17] Tanimoto A,Mukai M,Kuribayashi S. Evaluation of superparamagnedc iron oxide for MR imaging of liver injury:proton relaxation mechanisms and optimal MR imaging parameter.Magn Reson Med Sci, 2006, 5: 89-98. [18]洪国斌,周经兴,沈君,等.叶酸受体介导的肿瘤靶向超顺磁性纳米胶束的制备及体外实验.中华放射学杂志, 2008, 42: 19-23.
[1] Shimada M, Hashimoto E, Taniai M, et al. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis[J]. Hepatol, 2002, 37(1): 154-160.
[2] Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology, 2002, 123(1): 134-140.
[3] Tsujimoto T, Kawaratani H, Kitazawa T, et al. Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model. World J Gastroenterol, 2008, 14(39):6036-6043.
[4] Iijima H, Moriyasu F, Tsuchiya K, et al. Decrease in accumulation of ultrasound contrast microbubbles in non-alcoholic steatohepatitis. Hepatol Res, 2007, 37(9): 722-730.
[5]赵云辉,许乙凯.诱发性大鼠肝硬化性肝癌超顺磁性氧化铁增强MRI与电镜表现.临床放射学杂志, 2008, 27(12):1772-1776.
[6]艾正琳,陈东风,刘重阳,等.固醇调节元件结合蛋白-1c在大鼠非酒精性脂肪性肝炎中的表达及意义.重庆医学, 2007, 36(8):695-697.
[7]张宇,陈韶华,丁伟,等.酒精性肝病大鼠肝脏组织中铁的测定.浙江医学, 2004, 26(3):190-191.
[8] Abdelmalek MF, Diehl AM. Nonalcoholic fatty liver disease as a complication of insunlin resistance(Review). Med Clin North Am, 2007,91(6):1125-1149.
[9] Ishii H. Common pathogenic mechanisms in ASH and NASH. Hepatol Res, 2004, 28(1):18–20.
[10] Tsujimoto T,Kuriymas S,Yamazaki M,et a1.Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers. Int J Oncol, 2001, 18(1): 4l-47.
[11]吴惠文,许瑞龄.枯否细胞在非酒精性脂肪肝炎发生中的作用.医学研究通讯, 2005, 34(12):53-55.
[12] Okuhata Y. Delivery of diagnostic agents for magnetic resonance imaging.Adv Drug Deliv Rev, 1999, 37(1-3):121-137.
[13]杨华,张小明,邵阳,等.超顺性氧化铁在细胞内外对磁共振信号的影响.中国组织工程研究与临床康复, 2008, 12(30):5869-5872.
[14] Fatty Liver and Alcoholic Liver Disease Study Group of Chinese Liver Disease Association, Diagnosis and treatment guidelines for nonalcoholic fatty liver disease[J], Chin Hepatol, 2006,14(3):161-163.
[1]Bowman K, Leong KW. Chitosan nanoparticlos for oral drug and gene delivery[J]. IntJ Nanomedicine. 2006, l(2): 117-128.
[2]Chertok B, Moffat BA, David AE, et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials, 2008, 29(4): 487–496.
[3]Park K, Kim JH, Nam YS, et a1. Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles[J]. J Control Release, 2007, 122(3): 305-314.
[4]吴崇浩.纳米微粒表面修饰的研究进展[J].化工新型材料, 2002, 30(7): 1-5.
[5]王芳,陆菁菁,金征宇.新型磁共振对比剂USPIO及应用研究现状[J].国际医学放射学杂志, 2008, 31(5): 372-375.
[6]Lee JM, Kim CS, Youk JH, et a1. Characterization of focal liver lesions with superparamagnetic iron oxide-enhanced MR imaging: value of distributional phase T1-weighted imaging[J]. Korean J Radiol, 2003, 4(1): 9-18.
[7]Bush CH, Mladinich CR, Montgomery WJ. Evaluation of an ultrasmall superparamagnetie iron oxide in MRI in abone tumor model in rabbits[J]. J Magn Reson Imaging, 1997, 7(3): 579-584.
[8]Saokar A, Braschi M, Harisinghani M. Lymphotrophic nanopartiele enhanced MR imaging(LNMRI) for lymph node imaging[J]. Abdom Imaging, 2006, 31(6): 660-667.
[9]Tatsumi Y, Tanigawa N, Nishimura H, et a1. Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10[J]. Gastric Cancer, 2006, 9(2): 120-128.
[10]Saleh A, Schroeter M, Ringelstein A, et a1. Iron oxide particle-enhanced MRI suggests variability of brain inflammation at early stages after ischemic stroke[J]. Stroke, 2007, 38(10): 2733-2737.
[11]Saleh A, Schroeter M, Jonkmanns C, et a1. In vivo MRI of brain inflammatiun inhuman ischaemic stroke[J]. Brain, 2004, 127(7): 1670-1677.
[12]Tang TY, Howarth SP, Miller SR, et a1. Comparison of the inflammotory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: an uhrasmall superparamagnetic iron oxide enhanced magnetic ltsonanee study[J]. Eur J Vasc Endovasc Surg, 2008, 35(4): 392-398.
[13]Durand E, Raynaud JS, Bmneval P, et a1. Magnetic resonance imaging of ruptured plaques in the rabbit with ultrasmall superpaxamagnetie particles ofiron oxide[J].J Vasc Res, 2007, 44(2): 119-128.
[14]Dousset V, Brothel B, Deloire MS, et a1. MR imaging of relapsing multiple sclemsis patients using ultra-small-particle iron oxide and compared with gadolinium[J]. AJNR, 2006, 27(5): 1000-1005.
[15]Hanger O, Grenier N, Derninere C, et a1. USPIO—enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial resultsinhumans[J]. EurRadiol, 2007, 17(11): 2898-2907.
[16]Penno E, Johansson L, Ahlstrfim H, et a1. Ultrasmall iron oxide particle contrast agent and MRI can be used to monitor the effect of anti-rejection treatment[J]. Transplantation, 2007, 84(3): 374-379.
[17]Lutz AM, Seemsyer C, Corot C, et a1. Detection of synovial macrophages in an experimental rabbit model of antigen-induced arthritis: uhrasmall superparamagnetic iron oxide-enhanced MR imaging[J]. Radiology, 2004, 233(1): 149-157.
[18]Simon GH, Daldrup-Link HE, Rummeny EJ. Macrophage specific MRI imaging for antigen induced arthritides. A potential new strategy for the diagnosis of rheumatoid arthritis[J]. Radiologe, 2007, 47(1): 43-52.
[19]Lutz AM, Weishaupt D, Persohn E, et a1. Imaging of macrophages in soft tissue infection in rats: relationship between ultrasmall superparamagnetic iron oxide dose and MR signal characteristics[J]. Radiology, 2005, 234(3): 765—775.
[2] Greenfield V, Cheung O, Sanyal AJ. Recent advances in nonalcholic fatty liver disease. Curr Opin Gastroenterol, 2008, 24: 320-327.
[3] Polyzos SA, Kountouras J, Zavos C. Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med, 2009, 9:299-314.
[4] Kashi MR, Torres DM, Harrison SA. Current and emerging therapies in nonalcoholic fatty liver disease. Semin Liver Dis, 2008, 28: 396-406.
[5]孟二红,赵景民.非酒精性脂肪性肝炎的研究进展[J].世界华人消化杂志, 2002, 10:1206-1209.
[6] Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology, 1998, 114: 842-845.
[7]成军,李莉,张玲霞,等.丙型肝炎病毒感染与脂类代谢的相关性.肝脏, 2002, 7: 56-58.
[8] Tomita K, Tamiya G, Ando S, Ohsumi K, Chiyo T, Mizutani A, Kitamura N, Toda K, Kaneko T, Horie Y, Han JY, Kato S, Shimoda M, Oike Y, Tomizawa M, Makino S, Ohkura T, Saito H, Kumagai N, Nagata H, Ishii H, Hibi T. Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice. Gut, 2006, 55: 415-424.
[9] Shimada M, Hashimoto E, Taniai M, et al. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis[J]. Hepatol, 2002, 37(1): 154-160.
[10] Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology, 2002, 123(1): 134-140.
[11] Tsujimoto T, Kawaratani H, Kitazawa T, et al. Decreased phagocytic activity ofKupffer cells in a rat nonalcoholic steatohepatitis model. World J Gastroenterol, 2008, 14(39):6036-6043.
[12] Iijima H, Moriyasu F, Tsuchiya K, et al. Decrease in accumulation of ultrasound contrast microbubbles in non-alcoholic steatohepatitis. Hepatol Res, 2007, 37(9): 722-730.
[13] Okuhata Y. Delivery of diagnostic agents for magnetic resonance imaging.Adv Drug Deliv Rev, 1999, 37(1-3):121-137.
[14]杨华,张小明,邵阳,等.超顺性氧化铁在细胞内外对磁共振信号的影响.中国组织工程研究与临床康复, 2008, 12(30):5869-5872.
[15]赵朝辉,姚素薇,张卫国.纳米Fe_3O_4磁性颗粒的制备及应用现状[J].化工进展, 2005, 24: 865-868.
[1] Bowman K, Leong KW. Chitosan nanoparticlos for oral drug and gene delivery[J].IntJ Nanomedicine. 2006,l(2):117-128.
[2] Chertok B, Moffat BA, David AE, et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials, 2008, 29(4): 487–496.
[3] Park K,Kim JH,Nam YS,et a1.Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles[J].J Control Release,2007,122(3): 305-314.
[4]赵朝辉,姚素薇,张卫国.纳米Fe_3O_4磁性颗粒的制备及应用现状[J].化工进展, 2005, 24(8): 865-868.
[5]安江红,敖绪军,钱莘,等.壳聚糖纳米颗粒作为基因载体的初步研究.医学研究生学报,2008,21(8):790-794.
[6] Sobn BH, Cohen RE,Papaefthymiou GC, Magnetic properties of iron oxide nanoclusters within microdomains of block copolymers[J] . J Magn Magn Mater, 1998, 182: 216-224.
[7] Chertok B, Moffat BA, David AE, et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials, 2008, 29: 487-496.
[8]麦筱莉,滕皋军,马占龙,等.纳米磁粒子复合物标记对内皮祖细胞生物学特性影响的实验研究.中华放射学杂志, 2008, 42: 758-764.
[9]揭少卫,杨黎明,等.原位聚合法制备壳聚糖/聚丙烯酸水凝胶磁微球及其性能表征.高校化学工程学报, 2008, 22: 850-854.
[1] Lauffer RB. Magnetic resonance contrast media:principle and progress. Magn Reson Q, 1990, 6(2):65-84.
[2] Kim MJ, Kim JH, Choi JY, et al. Optimal TE for SPIO enhanced gradient recalled echo MRI for the detection of focal hepatic lesion. AJR Am J Roentgenol, 2006, 187(3): 255-266.
[3] Taupitz M, Schmitz S, Hamm B. Superparamagnetic iron oxide particles: current state and future development, Rofo 2003, 175(6): 752-765.
[4]景猛,刘新权,刘恩重.神经干细胞超顺磁性氧化铁纳米粒子标记和体内MRI示踪[J].中华神经外科疾病研究杂志, 2006,5(1):92-93.
[5] Tanimoto A, Mukai M, Kuribayashi S. Evaluation of superparamagnetic iron oxide for MR imaging of liver injury: proton relaxation mechanisms and optimal MR imaging parameter. Magn Reson Med Sci, 2006, 5(2):89-98.
[6]揭少卫,杨黎明,等.原位聚合法制备壳聚糖/聚丙烯酸水凝胶磁微球及其性能表征.高校化学工程学报, 2008, 22(5): 850-854.
[7] Chenga FY, Sua CH, Yanga TS, et al. Charecterization of aqueous dispersions of Fe_3O_4 nanoparticles and their biomedical applications. Biomaterials, 2005, 26(7): 729-738.
[8]许海燕.纳米技术在医学领域的应用研究.中华医学杂志, 2006, 86(8): 505-506.
[9]麦筱莉,滕皋军,马占龙,等.纳米磁粒子复合物标记对内皮祖细胞生物学特性影响的实验研究.中华放射学杂志, 2008, 42(7): 758—764.
[10] Frank JA,Miller BR,Arbab AS, et al. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology,2003, 228(2): 480-487.
[11]汪源浩,隋卫平,王恩峰.壳聚糖的化学改性及应用研究进展[J].济南大学学报,2007, 21(2): 140-144
[12]刘慧,壳聚糖微球/纳米粒的制备及其性能研究.浙江大学硕士学位论文,2007
[13] Okuhata Y.Delivery of diagnostic agcnts for magnetic resonance imaging.Adv Drug Deliv Rev, 1999, 37(1-3): 12l-137. [14]杨华,张小明,邵阳,等.超顺性氧化铁在细胞内外对磁共振信号的影响.中国组织工程研究与临床康复, 2008, 12(30): 5869-5872. [15] Simon GH, Bauer J, Sabomvski O, et a1. T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5 T and 3T clinical MR scanning.Eur Radiol, 2006, 16(3): 738-745. [16] Daldrup.Link HE,Rudelius M,Oostendorp RA,et a1.Targeting of hematopoietic progenitor cells with MR contrast agents.Radiology 2003,228(3):760-767. [17] Tanimoto A,Mukai M,Kuribayashi S. Evaluation of superparamagnedc iron oxide for MR imaging of liver injury:proton relaxation mechanisms and optimal MR imaging parameter.Magn Reson Med Sci, 2006, 5: 89-98. [18]洪国斌,周经兴,沈君,等.叶酸受体介导的肿瘤靶向超顺磁性纳米胶束的制备及体外实验.中华放射学杂志, 2008, 42: 19-23.
[1] Shimada M, Hashimoto E, Taniai M, et al. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis[J]. Hepatol, 2002, 37(1): 154-160.
[2] Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology, 2002, 123(1): 134-140.
[3] Tsujimoto T, Kawaratani H, Kitazawa T, et al. Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model. World J Gastroenterol, 2008, 14(39):6036-6043.
[4] Iijima H, Moriyasu F, Tsuchiya K, et al. Decrease in accumulation of ultrasound contrast microbubbles in non-alcoholic steatohepatitis. Hepatol Res, 2007, 37(9): 722-730.
[5]赵云辉,许乙凯.诱发性大鼠肝硬化性肝癌超顺磁性氧化铁增强MRI与电镜表现.临床放射学杂志, 2008, 27(12):1772-1776.
[6]艾正琳,陈东风,刘重阳,等.固醇调节元件结合蛋白-1c在大鼠非酒精性脂肪性肝炎中的表达及意义.重庆医学, 2007, 36(8):695-697.
[7]张宇,陈韶华,丁伟,等.酒精性肝病大鼠肝脏组织中铁的测定.浙江医学, 2004, 26(3):190-191.
[8] Abdelmalek MF, Diehl AM. Nonalcoholic fatty liver disease as a complication of insunlin resistance(Review). Med Clin North Am, 2007,91(6):1125-1149.
[9] Ishii H. Common pathogenic mechanisms in ASH and NASH. Hepatol Res, 2004, 28(1):18–20.
[10] Tsujimoto T,Kuriymas S,Yamazaki M,et a1.Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers. Int J Oncol, 2001, 18(1): 4l-47.
[11]吴惠文,许瑞龄.枯否细胞在非酒精性脂肪肝炎发生中的作用.医学研究通讯, 2005, 34(12):53-55.
[12] Okuhata Y. Delivery of diagnostic agents for magnetic resonance imaging.Adv Drug Deliv Rev, 1999, 37(1-3):121-137.
[13]杨华,张小明,邵阳,等.超顺性氧化铁在细胞内外对磁共振信号的影响.中国组织工程研究与临床康复, 2008, 12(30):5869-5872.
[14] Fatty Liver and Alcoholic Liver Disease Study Group of Chinese Liver Disease Association, Diagnosis and treatment guidelines for nonalcoholic fatty liver disease[J], Chin Hepatol, 2006,14(3):161-163.
[1]Bowman K, Leong KW. Chitosan nanoparticlos for oral drug and gene delivery[J]. IntJ Nanomedicine. 2006, l(2): 117-128.
[2]Chertok B, Moffat BA, David AE, et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials, 2008, 29(4): 487–496.
[3]Park K, Kim JH, Nam YS, et a1. Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles[J]. J Control Release, 2007, 122(3): 305-314.
[4]吴崇浩.纳米微粒表面修饰的研究进展[J].化工新型材料, 2002, 30(7): 1-5.
[5]王芳,陆菁菁,金征宇.新型磁共振对比剂USPIO及应用研究现状[J].国际医学放射学杂志, 2008, 31(5): 372-375.
[6]Lee JM, Kim CS, Youk JH, et a1. Characterization of focal liver lesions with superparamagnetic iron oxide-enhanced MR imaging: value of distributional phase T1-weighted imaging[J]. Korean J Radiol, 2003, 4(1): 9-18.
[7]Bush CH, Mladinich CR, Montgomery WJ. Evaluation of an ultrasmall superparamagnetie iron oxide in MRI in abone tumor model in rabbits[J]. J Magn Reson Imaging, 1997, 7(3): 579-584.
[8]Saokar A, Braschi M, Harisinghani M. Lymphotrophic nanopartiele enhanced MR imaging(LNMRI) for lymph node imaging[J]. Abdom Imaging, 2006, 31(6): 660-667.
[9]Tatsumi Y, Tanigawa N, Nishimura H, et a1. Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10[J]. Gastric Cancer, 2006, 9(2): 120-128.
[10]Saleh A, Schroeter M, Ringelstein A, et a1. Iron oxide particle-enhanced MRI suggests variability of brain inflammation at early stages after ischemic stroke[J]. Stroke, 2007, 38(10): 2733-2737.
[11]Saleh A, Schroeter M, Jonkmanns C, et a1. In vivo MRI of brain inflammatiun inhuman ischaemic stroke[J]. Brain, 2004, 127(7): 1670-1677.
[12]Tang TY, Howarth SP, Miller SR, et a1. Comparison of the inflammotory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: an uhrasmall superparamagnetic iron oxide enhanced magnetic ltsonanee study[J]. Eur J Vasc Endovasc Surg, 2008, 35(4): 392-398.
[13]Durand E, Raynaud JS, Bmneval P, et a1. Magnetic resonance imaging of ruptured plaques in the rabbit with ultrasmall superpaxamagnetie particles ofiron oxide[J].J Vasc Res, 2007, 44(2): 119-128.
[14]Dousset V, Brothel B, Deloire MS, et a1. MR imaging of relapsing multiple sclemsis patients using ultra-small-particle iron oxide and compared with gadolinium[J]. AJNR, 2006, 27(5): 1000-1005.
[15]Hanger O, Grenier N, Derninere C, et a1. USPIO—enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial resultsinhumans[J]. EurRadiol, 2007, 17(11): 2898-2907.
[16]Penno E, Johansson L, Ahlstrfim H, et a1. Ultrasmall iron oxide particle contrast agent and MRI can be used to monitor the effect of anti-rejection treatment[J]. Transplantation, 2007, 84(3): 374-379.
[17]Lutz AM, Seemsyer C, Corot C, et a1. Detection of synovial macrophages in an experimental rabbit model of antigen-induced arthritis: uhrasmall superparamagnetic iron oxide-enhanced MR imaging[J]. Radiology, 2004, 233(1): 149-157.
[18]Simon GH, Daldrup-Link HE, Rummeny EJ. Macrophage specific MRI imaging for antigen induced arthritides. A potential new strategy for the diagnosis of rheumatoid arthritis[J]. Radiologe, 2007, 47(1): 43-52.
[19]Lutz AM, Weishaupt D, Persohn E, et a1. Imaging of macrophages in soft tissue infection in rats: relationship between ultrasmall superparamagnetic iron oxide dose and MR signal characteristics[J]. Radiology, 2005, 234(3): 765—775.