大鼠肝硬化肝癌模型的建立及超顺磁性氧化铁纳米粒子增强前后磁共振成像表现

目的建立大鼠肝硬化肝癌模型，研究肝硬化背景下超顺磁性氧化铁纳米粒（SPIO）增强前后肝癌的检出率，并分析SPIO在大鼠肝硬化肝癌诱发过程中不同病变组织内分布变化情况，探讨其用于评估肝脏Kupffer细胞功能的可行性。方法30只雄性SD大鼠按完全随机分组的方法分成实验组20只和对照组10只，实验组予0．1mg／ml的二乙基亚硝胺（DENA）溶液自由饮用，对照组饮用灭菌生理盐水。实验组分别于给药后第10、20周各取10只先进行磁共振（MR）平扫，再注入SPIO后1h行MR增强扫描，大鼠扫描完成后立即处死。同理，对照组10只于第20周MR扫描完成后立即处死。分析MR图像，取血标本进行肝功能测定，取肝脏标本进行HE和普鲁士蓝染色病理学检查。两组间均数比较采用成组t检验，多组间均数比较采用方差分析，率的比较采用卡方检验。相关性分析采用Pearson’s相关分析。结果较之对照组，大鼠的AST及ALT10周组明显升高，20周组显著升高，3者间差异有统计学意义（P均〈0．001）。注入SPIO1h后增强扫描，肝脏组织信号强度下降百分比（PSIL）最大为正常肝组织，单纯性肝硬化、远癌肝硬化组织次之，肝癌组织最小，4者间PSIL差异有统计学意义（P〈0．001）。对于20周肝硬化肝癌组，SPIO增强后各序列上肝癌检出率明显提高，肝脏与病灶的对比噪声比（CNR）较增强前明显提高，增强前后差值有统计学意义（P〈0．05）。普鲁士蓝染色显示不同肝脏组织中的蓝染颗粒数与SPIO增强后MR各序列信号变化呈线性相关趋势，并具有统计学意义（P〈0．01）。结论DENA诱发sD大鼠肝硬化肝癌的模型与人类肝硬化肝癌的发生发展过程较为类似，通过SPIO增强MR扫描不但能间接反映不同病变组织中Kupffer细胞数量及功能状态变化，而且有利于肝硬化背景下早期肝癌结节的检出，对临床治疗具有重要的价值和指导意义。

Establishment of rat model of liver cirrhosis or liver cancer and its magnetic resonance images before and after super-paramagnetic iron oxide enhancement

Objective To establish a rat model of liver cirrhosis or liver cancer, to determine the liver cancer detection rates of magnetic resonance imaging （MRI） in liver cirrhosis before and after superparamagnetic iron oxide （SPIO） enhancement, to analyse the changes in SPIO distribution in different lesions in the process of inducing liver cirrhosis and liver cancer in rats, and to investigate the feasibility of as-sessing the function of Kupffer ceils by SPIO - enhanced MRI. Methods Thirty male Sprague - Dawley （SD） rats were randomly divided into experimental group （n = 20） and control group （n = 10 ）. The experimental group was given 0.1 mg/ml diethylnitrosamine （DENA） solution by free drinking, while the control group drank sterilized saline. At 10 or 20 weeks after treatment, 10 rats were selected from the experimental group to undergo plain MRI scans and then SPIO - enhanced MRI performed one hour after injection of SPIO ; the rats were sac- rificed immediately after scans. At 20 weeks after treatment, the 10 rats in control group underwent MRI scans and were then sacrificed im-mediately. The obtained MR images were analyzed. Blood samples were taken to measure serum alanine aminotransferase （ALT） and aspar-tare aminotransferase （AST） levels. Liver samples were taken and subjected to HE staining and Perls＇ blue staining for pathological examina-tion. Results Compared with the control group, the experimental group had significantly increased ALT and AST levels at 10 weeks （P 〈 0. 001 ） , and the ALT and AST levels were significantly higher at 20 weeks than at 10 weeks in the experimental group （P 〈0. 001 ）. The SPIO - enhanced MRI showed that the percentage of signal intensity loss （PSIL） was the highest in normal liver tissue, followed by simple cirrhosis tissue and cirrhosis tissue distant from liver cancer, and was the lowest in liver cancer tissue; there were significant differences in PSIL between the four tissues （ P 〈 0. 001 ）. In the experimental rats examined at 20 weeks after treatment, the liver cancer detection rate on each sequence and lesion - to - liver contrast - to - noise ratio increased significantly after SPIO enhancement （ P 〈 0.05 ）. The Perls＇ blue staining showed that there was a significant linear correlation between the number of blue dye particles and PSIL on each sequence after SPIO enhancement in various liver tissues （ P 〈 0.01 ）. Conclusion DENA induces the SD rat model of liver cirrhosis or liver cancer by the process similar to the development and progression of liver cirrhosis and liver cancer in humans. SPIO - enhanced MRI not only can indirect-ly reflect the changes in number and function of Kupffer cells in various lesions, but is also conducive to the early detection of liver cancer nodules in liver cirrhosis, with important value and guiding significance for clinical treatment.