运用MRI评估超顺磁性氧化铁纳米粒在肝硬化肝癌组织中分布变化的实验研究  

Experimental research on application of MRI in assessing the distribution of superparamagnetic iron oxide nanoparticles in cirrhosis liver cancer tissue

作　　者：黄瑞岁[1,2] 李澄[1,2] 顾晗[1,2] 焦志云[1,2] 成维艳[1,2] 

机构地区：[1]扬州市第一人民医院 [2]扬州大学第二临床医学院放射科,江苏扬州225001

出　　处：《生物医学工程与临床》2013年第4期305-311,共7页Biomedical Engineering and Clinical Medicine

基　　金：国家自然科学基金资助项目(30970812)

摘　　要：目的研究超顺磁性氧化铁纳米粒(SPIO)作为MRI对比剂在肝硬化肝癌组织中分布变化情况,探讨其用于分子靶向成像的可行性。方法 SPF级雄性SD大鼠35只,体质量(200±20)g,鼠龄3个月。按完全随机分组的方法分成实验组25只和对照组10只,实验组予质量浓度0.1mg/mL的二乙基亚硝胺(DENA)溶液自由饮用,对照组饮用灭菌0.9%氯化钠溶液。于给药后20周先进行MRI平扫,再注入SPIO后1、24、48、72、96h分别行MRI增强扫描,每一时段5只。同理,空白对照组每一时段取2只。分析MRI图像,取血液标本进行肝功能测定,取肝脏标本进行苏木精-伊红和普鲁士蓝染色病理学检查。结果实验组大鼠肝功能指标丙氨酸氨基转移酶及天冬氨酸转氨酶[分别为(130.43±8.83)、(415.00±55.44)U/L]较对照组[分别为(39.57±7.25)、(132.93±39.03)U/L]显著升高(P<0.001)。正常肝组织及肝硬化组织,注入SPIO后1 h,各序列上肝脏组织信号明显下降,24 h肝脏组织信号强度下降百分比(PSIL)达到最大,48、72、96 h后均下降,各时段PSIL差异有统计学意义(P<0.001);而20周肝癌组织,注入SPIO各时段其信号无明显变化(P>0.05)。普鲁士蓝染色显示,正常肝组织及肝硬化组织蓝染的Kupffer细胞数在24 h达到最多,后逐步减少;部分高分化肝癌组织散在少许蓝染的Kupffer细胞,低分化肝癌组织内无蓝染细胞。不同肝脏组织SPIO增强后MRI各序列信号变化与组织中蓝染的Kupffer细胞数呈线性相关趋势,具有显著统计学意义(r正常=0.927,r肝硬化=0.912,P<0.01)。结论通过MRI扫描动态观察SPIO分布变化情况,不仅可用于肝脏恶性病变的检出,而且具有将SPIO作为MRI对比剂用于分子靶向成像的潜能。Objective To investigate the feasibility of application of superparamagnetic iron oxide nanoparticles（SPIO） as MRI contrast agent for targeted molecular imaging of cirrhosis liver cancer.Methods Thirty-five male SD rats[body weight（200 ± 20） g,aged 3-month）] were randomly divided into experimental group（n = 25） and control group（n = 10）.The experimental group was fed with free drink of 0.1 mg/mL diethylnitrosamine（DENA） solution,whereas control group was fed with sterilized physiological saline.Twenty weeks after the treatment,plain MRI was performed before performance of SPIO enhanced MRI at 1-hour,24-hour,48-hour,72-hour and 96-hour after injection of SPIO（5 rats in the experimental group and 2 rats in control group at each time point）.The blood anine aminotransferase（ALT） and aspartate aminotransferase（AST） were measured at each time point.The rats were sacrificed immediately after scanning,and hematoxylin-eosin（HE） and Prussian’s blue staining were performed to analyze the liver tissue.Results The ALT and AST levels in experimental group[（130.43 ± 8.83） U/L and（415.00 ± 55.44） U/L,respectively] were significantly higher than that in control group[（39.57 ± 7.25） U/L and（132.93 ± 39.03） U/L,respectively]（P 〈0.001）.1-hour after injection of SPIO,signals of normal liver tissue and the cirrhosis tissue adjacent to carcinoma declined obviously in each sequence.The percentage of signal intensity of liver（PSIL） reached maximum in 24-hour,and then successively decreased after 48-hour,72-hour and 96-hour,with statistically significant differences（P 〈0.001）.Prussian’s blue staining showed that the number of blue stained Kupffer cells in the normal liver tissue and carcinoma side cirrhosis tissue was the highest at 24-hour,and then phased down.A part of the highly differentiated liver cancer tissue had a few scattered blue stained Kupffer cells,and no blue stained Kupffer cell was observed in the poorly differentiated liver cancer tissue.There

关 键 词：肝硬化肝癌 磁共振成像 氧化铁纳米粒 靶向治疗 

分 类 号：R575.2[医药卫生—消化系统] R735.7[医药卫生—内科学]