Rypácek F, Drobník J, Chmelar V, Kálal J
Pflugers Arch. 1982 Jan;392(3):211-7. doi: 10.1007/BF00584298.
Five derivatives of polyaspartamide were used as macromolecular models to study the effect of chemical structure of macromolecules on their renal excretion and retention. The parent polymer was formed solely by N(2-hydroxyethyl)aspartamide units (I) and in its derivatives about 20% of 2-hydroxyethyl groups were randomly replaced by either n-butyl- (II), 2(4-hydroxyphenyl)ethyl- (III, N- dimethylamino propyl- (IV) or the aspartamide unit was modified to free aspartic acid carboxyl (V). The rate of clearance from the serum, the deposition in the kidney tissue in comparison with the deposition in reticuloendothelial system organs-liver and spleen, as well as tissue and cellular localisation of deposits were studied on rabbits and mice taking advantage of fluorescence labelling. The clearance of macromolecular models from the serum compartment by the glomerular filtration is mainly molecular weight controlled, while the retention of macromolecules possessing the same molecular weight by the kidney tubular epithelium is strongly affected chemical modification. About thirty and hundred times higher retentions due to reabsorption in proximal tubule were found with macromolecular models II and III respectively.
五种聚天冬酰胺衍生物被用作大分子模型,以研究大分子化学结构对其肾脏排泄和潴留的影响。母体聚合物仅由N(2-羟乙基)天冬酰胺单元(I)构成,在其衍生物中,约20%的2-羟乙基基团被正丁基(II)、2(4-羟苯基)乙基(III)、N-二甲基氨基丙基(IV)随机取代,或者天冬酰胺单元被修饰为游离天冬氨酸羧基(V)。利用荧光标记,在兔和小鼠身上研究了血清清除率、与网状内皮系统器官(肝脏和脾脏)中的沉积相比肾脏组织中的沉积,以及沉积物的组织和细胞定位。通过肾小球滤过从血清区室清除大分子模型主要受分子量控制,而具有相同分子量的大分子被肾小管上皮潴留则受到化学修饰的强烈影响。分别在大分子模型II和III中发现,由于近端小管重吸收导致的潴留分别高出约30倍和100倍。