超顺磁性氧化铁MR成像评估大鼠非酒精性脂肪肝炎枯否细胞功能的初步研究

目的 初步探讨超顺磁性氧化铁(SPIO)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SPIO增强扫描,计算肝脏组织平均信号强度下降百分比(PSIL)和SPIO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和普鲁士蓝染色分析病理表现.采用两组独立样本均数t检验比较2组不同序列SPIO增强后PSIL和RSIR值的差异.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)和(1.53±0.23)mmoL/L,较对照组分别为(1.64±0.22)和(0.55±0.14)mmol/L]均明显升高(t值分别为11.716和11.588,P值均＜0.01).SPIO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T_1WI上实验组PSIL分别为(34.78±4.51)%和(60.38±3.49)%,较实验组分别为(64.96±2.42)%和(81.08±1.66)%]小,差异有统计学意义(t值分别为-18.451和-16.240,P值均＜0.01).PDWI、T_2WI、T_2~*WI和T_1WI序列实验组RSIR分别为1.002±0.141、5.000±0.516、20.004±1.490和2.601±0.077,均较对照组(0.400±0.102、1.500±0.115、0.503±0.105和-0.300±0.058)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1.5 T MR通过SPIO增强肝脏扫描可评估KC的功能,提示NASH的发病机制与KC功能的下降有关.

A primary study on the phagocytic activity of Kupffer cells with superparamagnetic iron oxide particles enhanced MR imaging in a rat nonalcoholic steatohepatitis model

Objective To investigate the feasibility of using superparamagnetic iron oxide(SPIO)as MRI contrast agent to assess rat nonalcoholic steatohepatitis Kupffer cells(KC)function.Methods Twenty male SD rats were randomly divided into A and B groups,group A(n=10)was the experimental group fed high fat diet,group B(n=10)was the control group fed normal diet After 8 weeks,plain MR and SPIO enhanced MR 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 results of the staining were analyzed with t test Results Group A TC and TG levels(6.58±1.25)and(1.53±0.23)mmol/L respectively]were significantly higher than group B(1.64±0.22)and(0.55±0.14)mmol/L respectively](t=11.716 and 11.588,P＜0.01).Group A and B groups hepatic signal intensity decreased in all sequences after SPIO enhanced,but in group A the level of decline(34.78±4.51)% and(60.38±3.49)% respectively]was less than group B(64.96±2.42)% and(81.08±1.66)% respectively]on PDWI and T_1WI,and statistically significant differences(t=-18.451 and-16.240,P＜0.01)were found.In group A 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 respectively)was more than group B(0.400±0.102,1.500±0.115,0.503±0.105 and-0.300±0.058)before and after contrast enhancement on PDWI,T_2WI,T_2~* WI andT_1WI(t=10.745,19.800,39.168 and 92.785,P＜0.01).Typical histological hepatic lesions of NASH were observed in group A,Perl's staining-positive particles in group A(2.33±0.50)were fewer than in group B(4)(t=-10.000,P＜0.01).Conclusion The high-fat diet induced model of SD rats was close to the human NASH and was easy to establish.Clinical application of SPIO enhanced MR successfully assessed the phagocytic activity of KC in the study,and it suggested that the pathogenesis of NASH was related to the decreased phagocytic activity of KC.