摘要
目的:研究基因重组人肿瘤坏死因子衍生物α(rhTNFαDa)的组织分布及其机制。方法:用Iodogen法制备^(125)I-rhTNFαDa,测定在小鼠全身组织的分布;用离体心肺灌流研究^(125)I-rhTNFαDa在肺组织的分布机制。结果:除甲状腺组织外,^(125)I-rhTNFαDa的组织浓度-时间曲线下面积在肺组织中最高,为血清的12.2倍;离体心肺灌流显示^(125)I-rhTNFαDa在肺中的浓度高于灌流液3.7-7.4倍,而心脏组织低于灌流液.^(125)I-rhTNFαDa在肺中分布具有时间依赖性,剂量依赖性,可竞争性,和高亲和性特征,K_d为47.6 pmol·L^(-1),B_(max)为348 fmol·g^(-1)(肺组织),结论:^(125)I-rhTNFαDa在肺组织中有特异性的高分布,此过程可能有受体介导。
AIM: To study the tissue distribution and its mechanism of a new recombinant tumor necrosis factor alpha derivative (rhTNFαDa) in mice. METHODS: 125I-rhTNFαDa was prepared by Iodogen method. Tissue distribution of 125I-rhTNFαDa in mice was studied by determining radioactivity of tetrachloroacetic acid (TCA)- precipitable fraction in tissues. The isolated heart-lung perfusion study using 125I-rhTNFαDa perfusate was carried out to study the distribution characteristics of 125I-rhTNFαDa in lung. RESULTS: Except for thyroid, AUC of the TCA-precipitable 125I-rhTNFαDa in tissues was highest in lung, which was 12.2-fold of that in serum, while concentrations in other tissues were all lower than that in serum. Perfusion study in vitro revealed that the concentration of radio-labeled peptide in lung was higher than that in perfusate. On the contrary, level in heart was much lower than that in perfusate. The overall distribution of 125I-rhTNFαDa in lungs showed rapidly equilibratory, dose-dependent, saturable, competitive, and highly affinitive, with Kd47.6 pmol·L-1 and Bmax 348 fmol·g-1 (lung tissue). CONCLUSION: The specific distribution of rhTNFαDa in lungs was its distinctive characteristics.
出处
《中国药理学报》
CSCD
1999年第4期371-374,共4页
Acta Pharmacologica Sinica
关键词
肿瘤坏死因子
组织分布
受体
rhTNF2
衍生物
tumor necrosis factor
tissue distribution
receptor
lung
heart-lung perfusion
