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三种不同给药途径后小鼠体内肽聚糖单体的代谢与免疫刺激活性的关系

Relationship of metabolism and immunostimulating activity of peptidoglycan monomer in mice after three different routes of administration.

作者信息

Valinger Z, Ladesić B, Hrsak I, Tomasić J

出版信息

Int J Immunopharmacol. 1987;9(3):325-32. doi: 10.1016/0192-0561(87)90057-9.

Abstract

[14C] Peptidoglycan monomer, GlcNAc-MurNAc-L-Ala-D-isoglutamine-meso-diaminopimelic acid (omega NH2)-D-Ala-D-Ala (PGM) was administered to mice by the intravenous (i.v.), subcutaneous (s.c.) or peroral (p.o.) routes. The data on distribution of radioactivity and excretion of radioactive products, as well as the data on immunostimulating effects are presented on the comparative basis for PGM administered by three different routes. When injected i.v. or s.c., the major part of applied radioactivity was found excreted in urine, partly as unchanged original compound and partly as the corresponding pentapeptide, L-Ala-D-isoglutamine-meso-diaminopimelic acid (omega NH2)-D-Ala-D-Ala. If administered p.o., the major part of the radioactivity was retained in the stomach and intestinal tract for several hours. The drop in radioactivity in these organs was followed by exhalation of 14CO2 thus indicating extensive degradation of the original molecule. PGM stimulates the humoral immune response to sheep red blood cells in mice if administered i.v. or s.c., but is completely inactive if administered p.o.. Thus, absence of immunostimulating activity following p.o. administration might be explained by extensive metabolic degradation of peptidoglycan monomer.

摘要

将[14C]肽聚糖单体,即N-乙酰葡糖胺-胞壁酸-L-丙氨酸-D-异谷氨酰胺-内消旋二氨基庚二酸(ω-NH2)-D-丙氨酸-D-丙氨酸(PGM)通过静脉内(i.v.)、皮下(s.c.)或口服(p.o.)途径给予小鼠。关于放射性分布和放射性产物排泄的数据,以及关于免疫刺激作用的数据,以比较的方式呈现了通过三种不同途径给予PGM的情况。静脉内或皮下注射时,所给予放射性的主要部分在尿液中排泄,部分以未改变的原始化合物形式,部分以相应的五肽,即L-丙氨酸-D-异谷氨酰胺-内消旋二氨基庚二酸(ω-NH2)-D-丙氨酸-D-丙氨酸形式排泄。如果口服给药,放射性的主要部分在胃和肠道中保留数小时。这些器官中放射性的下降随后伴随着14CO2的呼出,从而表明原始分子发生了广泛降解。如果静脉内或皮下给药,PGM可刺激小鼠对绵羊红细胞的体液免疫反应,但口服给药则完全无活性。因此,口服给药后缺乏免疫刺激活性可能是由于肽聚糖单体的广泛代谢降解所致。

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