人表皮生长因子的基础和应用研究  

The Basic and Applied Study on the Epidermal Growth Factor

作　　者：黄秉仁[1] 蔡良婉[1] 向绪传[1] Xiang-Xu-zhuan 

机构地区：[1]中国医学科学院中国协和医科大学基础医学研究所生物化学与分子生物学研究室,,北京100005 [2]Middle-Scale Experimental Base of the Institute of Basic Medical Sciences, CAMS PUMC and Jin Ke Company, Guilin,

出　　处：《中国医学科学院学报》2001年第2期176-180,共5页Acta Academiae Medicinae Sinicae

基　　金：国家"八五""九五"科技攻关项目&&

摘　　要：本文报道了有关人表皮生长因子（ hEGF）及其受体（ EGFR）的基础研究结果，以及在此基础上进行新药开发的有关工作： hEGF的基因合成、表达载体的构建和转化宿主细胞、表达产物的纯化和中试规模三批样品的生产和检验等的有关研究结果、 hEGF滴眼液的动物实验和临床实验等新药研制过程。有关基础研究表明，编码 51个氨基酸的 hEGF可以在α因子前导肽的引导下在酵母体系中分泌性表达，表达产物可促进角膜缘上皮细胞的增殖，可促进角膜碱烧伤的愈合，可用于口腔溃疡和皮肤烧伤的治疗，可对大鼠十二指肠溃疡有预防作用等 ,并用之制备了抗血清以测定血尿中 EGF的浓度。研究表明 EGF在大于 10 ng/ml浓度下对神经胶质瘤细胞株 BT325和人阴道上皮癌细胞株 A431的生长具有抑制作用，并用差异显示方法对此现象进行了分子机制的探讨。研究肾癌 EGFR表达和 DNA含量检测具有临床意义。对 EGF的晶体进行了初步的结构分析。中试产品检测表明 hEGF相对分子质量为 6000、等电点为 4.6、氨基端 15个氨基酸顺序正确、具有 EGF的免疫原性和生物活性。产品中无酵母细胞的残余 DNA。动物实验表明 EFG在体内无蓄积，有明确的促进角膜上皮细胞增殖的作用，无急毒和长毒副作用，对眼无刺激和局部毒性作用。在四家医院进行的多中?This article reviews the results of the basic research about epidermal growth factor and its receptor, and the development of the novel drug, EGF eyedrop, that containing chemically synthesized EGF gene ,the construction of EGF expression vector, the transformation of the host cells ,the purification of the recombinant protein EGF , the preparation of three batches of the EGF product and identification, the preclinical and clinical trials. Relevant studies show that recombinant EGF consisting of 51 amino acids can be secreted into the medium under the control of theα factor leading sequence in the yeast c ells. The EGF can accelerate the growth of corneal-limbal epithelial cells and the healing of an alkali burned corneal. The EGF can be used in curing oral cavity ulcer and skin burned wound. And it has the preventive effects on experimental duodenal ulcer of rat. The antiserum was made for test of the concentration of blood EGF and urine EGF by RIA.Data from studies demonstrate the inhibition effect of EGF on the growth of tumor cells, such as A431 and BT325 cells in the presence of high EGF concentration (? 10 ng/ml).The expression of EGFR and DNA ploidy in renal carcinoma has clinical significance.Crystallization and preliminary x-ray diffraction studies of the EGF has been made. The MW of the EGF product is 6000, and the pI is about 4.6 and it has correct N-terminal amino acids sequences , immunogenicity and biological activity. There is no vestige of the DNA of the yeast cells. Animal experiments reveal that there is no cumulation of the EGF in the body, and EGF can promote corneal epithelial healing. There is no toxicological effect during cornea wound healing of rabbit. A randomized, double-blind, placebo-controlled, multi-center clinical trial was conducted in four hospitals to assess safety, ocular tolerance and efficacy of an ophthalmic solution of EGF for 200 cases of cornea transplantation and 247 cases of nebulae. Unequivocal results were obtained as the eyedrop really accelerate the wounded co

关 键 词：表皮生长因子 受体 重组蛋白 滴眼液 基因工程药 

分 类 号：R988.1[医药卫生—药品] R997[医药卫生—药学]