论文部分内容阅读
化学合成了去唾液酸糖蛋白受体 (ASGPR) 的配基—新半乳糖人血清白蛋白(NGA);参照 Marshl 法制备了 FITC-人血清白蛋白(HSA)和 FITC-NGA;直接法制备了 99mTc-NGA。以 FITC-HSA为参照,FITC-NGA 示踪流式细胞术(FCM)分析显示正常肝细胞、慢性肝损伤细胞和肝癌细胞表面的 ASGPR 的含量有显著差异,它们的 MIF 值分别为 228.7、5.81 和 1.13,并随细胞损伤程度加剧 MIF值呈下降的趋势。正常肝细胞表面约有 8×106 个 ASGPR,1×106个/ml 肝细胞的 FITC-NGA 饱和浓度约为 0.4 μg/ml,且此结合可被50 倍量的 NGA 所抑制。说明 NGA 是 ASGPR 的特异性配基;肝癌细胞表面几乎没有 ASGPR。小鼠体内分布实验表明 99mTc-NGA能够被肝脏特异摄取,且具饱和性,其它脏器摄取均较低,肠道放射性随时间增加而增加。正常及模型动物 Tc-NGA 体内动态显像 99m研究表明正常动物较肝损害动物血本底清除快,且此显像能被 NGA竞争性抑制;简单动态分析显示正常组与肝损害组肝脏与心脏的放射性—时间曲线差别明显,两者“受体指数”分别为 0.980±0.010,0.949±0.025(n = 6)。
The aspartate-neogalactosyl-human serum albumin (NGA) was chemically synthesized as ASGPR. FITC-HSA and FITC-NGA were prepared by the Marshl method. 99mTc-NGA. FITC-HSA as a reference, FITC-NGA tracer FCM analysis showed that the content of ASGPR on the surface of normal liver cells, chronic liver injury cells and liver cancer cells were significantly different, their MIF values were 228.7,5.81 And 1.13, and with the degree of cell damage aggravate the MIF value showed a downward trend. About 8 × 106 ASGPRs are found on the surface of normal liver cells. The saturation concentration of FITC-NGA in 1 × 106 cells / ml hepatocytes is about 0.4 μg / ml, and this binding can be inhibited by 50 times the amount of NGA. NGA is a specific ligand of ASGPR; almost no ASGPR on the surface of liver cancer cells. In vivo experiments in mice showed that 99mTc-NGA was specifically uptaked by the liver and was saturated with low uptake by other organs and increased intestinal radioactivity with time. In vivo dynamic imaging of normal and model animals Tc-NGA 99m study showed that normal animals than the liver damage animals blood background clearance fast, and this imaging can be NGA competitive inhibition; simple dynamic analysis showed that the normal group and liver damage group liver and heart The difference of radioactive-time curve was obvious. The “receptor index” of the two were 0.980 ± 0.010 and 0.949 ± 0.025 respectively (n = 6).