【摘要】 目的　通过对肝细胞去唾液酸糖蛋白受体 (ASGPR)功能的体内外分析来区别正常肼脏与慢性肝脏损害。方法　采用吸入CCl4 法建立慢性肝损害大鼠模型 ,用流式细胞仪 (FCM)技术异硫氰酸荧光素 新半乳糖人血清白蛋白 (FITC NGA)进行体外受体分析。SnCl2 还原法制备99Tcm NGA ,进行小鼠体内分布和正常及慢性肝损害模型大鼠ASGP受体显像研究。结果　FITC NGA结合的荧光道数值随肝损害程度的增加而降低。99Tcm NGA能迅速被肝脏摄取 ,其它脏器摄取均较低 ,肠道放射性随时间增加而增加。99Tcm NGA受体动态显像结果表明正常大鼠血本底清除快 ,注射 5min后肝脏显影清晰 ,而肝损害模型大鼠血本底清除较慢 ,注射 5min后 ,心、肺影仍存在 ,肝脏轮廓不清晰。简单动态分析显示 ,正常及肝损害模型大鼠心脏及肝脏的时间 放射性曲线差别较明显。“清除指数”HH15分别为 0 6 75± 0 10 6和 0 6 96± 0 10 3:“受体指数”LHL15分别为 0 980± 0 0 10和 0 949±0 0 2 5。结论　体外FCM分析可从细胞水平反映正常及损伤肝细胞ASGPR数量的变化。99Tcm NGA肝受体动态显像可反映肝细胞受体功能 ,而LHL15可较好反映肝细胞受体数量。更多还原

【Abstract】 Objective To evaluate the effects of functional analysis of hepatic asialoglycoprotein receptors (ASGPR) for differentiating diseased liver from the normal ones in vitro and in vivo Methods The rat model of chronic liver disease was established with inhaling CCl 4.Galactosylneoglycoalbumin (NGA) was labeled with fluorescien isothiocyanate (FITC) by Marshal’s method, or was labeled directly with Na 99 Tc mO 4 by SnCl 2 method The ASGPR on hepatocytes was analyzed by flow cytometry method (FCM) in vitro and by SPECT in vivo ResultsIt was showed that the amounts of ASGPR on normal and injured hepatocytes were very different in vitro The worse the hepatocytes were injured, the lower the mean intensity of fluorescein (MIF) would be detected.Biodistribution analysis in animals showed that 99 Tc m NGA could be uptaken fast by liver, no significant accumulation in other organs was obtained Intestinal accumulation was also minimal and increased with time, that indicated the major excretory route of 99 Tc m NGA was the biliary system and, eventually, the gastrointestinal tract The blood clearance was fast in normal animals but retarded in liver injured model animals The simple kinetics analysis indicated that radioactivity curves overtime of both hearts and livers in normal animals were obviously different from those in model animals The receptor indexes (LHL 15 ) were 0 980±0 010 and 0 949±0 025, and the clearance indexes (HH 15 ) were 0 675±0 106 and 0 696±0 103 respectively Conclusions The FCM is a good method for analyzing the amount of ASGPR on the surface of normal and injured heptocytes in vitro Hepatic imaging using 99 Tc m NGA can reflect specific hepatocyte function as the radioligand is metabolized only by the ASGPR on hepatocytes As hepatic uptake of 99 Tc m NGA and LHL 15 analysis is sensitive for quantitation of ASGPR , fairly good estimation of liver function in liver disease is possible based on visual 99 Tc m NGA imaging of the liver alone更多还原