靶向性超声显影评价不同程度肝损伤的初步实验研究

摘要

目的 使用靶向超声分子显像对比分析大鼠不同程度急性肝损伤后峰值回声强度的改变与去唾液酸糖蛋白受体(ASGPR)的含量及血清学检查的关系.方法 根据腹腔灌注四氯化碳分析纯的不同剂量(10%、20%、30%、40%、50%),将45只健康雄性SD大鼠随机分为相应5组(组Ⅰ~组Ⅴ),每组9只,每组中再随机抽取4只取肝组织,分别检测ASGPR的含量;另5只仅常规麻醉,胸腹部备皮,经尾静脉团注靶向液态氟碳纳米脂质超声造影剂.从注射开始至0.5 h内连续观察并记录,0.5～1 h内每10 min观察并记录,1 h至造影剂消退每30 min观察并记录肝实质超声图像.DFY型超声图像定量分析诊断仪对各时间点采集到的超声图像进行分析.另选10只健康雄性SD大鼠作为靶向超声造影对照组,方法同前.结果 随着肝损伤程度的增加,肝组织内的ASGPR含量逐渐减少,且各组样本均数两两比较差异均有统计学意义(P0.05).结论 自制靶向肝实质细胞膜受体ASGPR的液态氟碳纳米超声造影剂的肝靶向性显影效果佳;不同程度肝损伤后的靶向超声显影结果改变与ASGPR结果改变一致,有利于超声显影定量评价肝脏功能.%Objective To comparatively analyze the relationship of peak - echo intensity of targeted ultrasound molecular imaging and asialoglycoprotein receptor ( ASGPR) content in different degree of rat acute liver injury. Methods Acute liver injury model was established by intraperitoneal infusion of carbon tetrachloride ( CCl4 ) in 45 healthy male SD rats,the rats were divided int0 5 groups ( group Ⅰ - groupⅤ ) according to doses of CCl4 ( 10％ ,20％ ,30％ ,40％ ，50％ ) with 9 rats in each group. The content of liver ASGPR in 4 rats of each group was detected respectively. The others were anesthetized generally , thoracic and abdominal skin was prepared, the liquid perfluorocarbon nanoparticles targeted ultrasound contrast agents were injected through the tail vein with bolus injection. From the beginning t0 0. 5 h， the ultrasonic imaging was observed and recorded continuously; from 0.5 h to 1 h, the ultrasonic imaging was observed and recorded in each 10 min; from 1 h to the regression of contrast agents , the ultrasonic imaging of the liver parenchyma was observed and recorded in each 30 min. Finally,the ultrasonic images of the liver parenchyma at different time points were analyzed by DFY diagnostic ultrasound image analysis system. Another 10 healthy male SD rats were used as control group. Results With the increase of liver damage, the ASGPR content of liver tissue was decreased , there was significant difference between the groups(P ＜ 0. 05 ) ; with the increase of injury degree , the peak echo intensity of liver was decreased , there was significant difference between the groups ( P ＜ 0. 05 ) , except the normal control group and group Ⅰ (P ＞ 0. 05). While there was no significant difference of time to peak, peak intensity, parenchyma intensity before enhancement and parenchyma intensity after wash - out of contrast agents( P ＞ 0. 05 ) . Conclusion The imaging of liver injury with liquid perfluorocarbon nanoparticles ultrasound contrast agents targeted to liver cell membrane receptors ASGPR is excellent. the changes of peak intensity in ultrasound targeted imaging are consistant with those of ASGPR,which has benefit for quantitative evaluation of liver reserve function.