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血液和骨髓对环磷酰胺治疗的一氧化氮反应。

Nitrergic response to cyclophosphamide treatment in blood and bone marrow.

作者信息

G A Kevorkian, N Kh Alchujyan, N H Movsesyan, H L Hayrapetyan, A G Guevorkian, R M Ohanyan, S S Dagbashyan

机构信息

H. Buniatian Institute of Biochemistry NAS RA, 5/1 P.Sevak St., 0014, Yerevan, Republic of Armenia.

出版信息

Open Biochem J. 2008;2:81-90. doi: 10.2174/1874091X00802010081. Epub 2008 Jun 3.

DOI:10.2174/1874091X00802010081
PMID:18949079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2570548/
Abstract

Daily intraperitoneal injection of cyclophosphamide (CPA) (50 mgkg(-1) of body weight) for 5 days resulted in reduced levels of marrow and blood cellularity, which was most pronounced in 18 days post-treatment (pt). On day 18 after CPA treatment the enhancedlevels of nitric oxide (NO) precursors and metabolites (L-arginine, L-citrulline, reactive nitrogen species (RNS)) of marrow and blood cells (platelet, neutrophil, lymphocyte and monocyte) resulted from up-regulation of Ca(II)/calmodulin(CaM)-independent "inducible" NO synthase (iNOS), with a lessercontribution of Ca(II)/CaM-dependent "constitutive" cNOS isoforms to systemic NO.Biphasic response to CPA of marrow nitrergic system, i.e. both iNOS and cNOS showed significantly depressed activities, as well as diminished levels of NO metabolites on day 9 pt, suggested that signals in addition to NO might be involved in CPA-induced inhibition of hematopoesis, while a gradual increase of neutrophil and platelet NOS activity appeared to be contributed to a CPA-induced development of granulopenia, thrombocytopenia and hemorrhage.

摘要

连续5天每天腹腔注射环磷酰胺（CPA）（50毫克/千克体重）导致骨髓和血细胞数量减少，在治疗后18天最为明显。在CPA治疗后的第18天，骨髓和血细胞（血小板、中性粒细胞、淋巴细胞和单核细胞）中一氧化氮（NO）前体和代谢物（L-精氨酸、L-瓜氨酸、活性氮物质（RNS））水平升高，这是由于钙（II）/钙调蛋白（CaM）非依赖性“诱导型”NO合酶（iNOS）上调所致，而钙（II）/CaM依赖性“组成型”cNOS同工型对全身NO的贡献较小。骨髓硝化系统对CPA的双相反应，即在治疗后第9天iNOS和cNOS的活性均显著降低，以及NO代谢物水平降低，表明除NO外的信号可能参与了CPA诱导的造血抑制，而中性粒细胞和血小板NOS活性的逐渐增加似乎导致了CPA诱导的粒细胞减少、血小板减少和出血。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/086f2937c4a8/TOBIOCJ-2-81_F10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/605684aaa720/TOBIOCJ-2-81_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/8c74a5d4c016/TOBIOCJ-2-81_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/187f1c55e5a6/TOBIOCJ-2-81_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/b911ef3565fc/TOBIOCJ-2-81_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/4d5a5a7d9f00/TOBIOCJ-2-81_F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/46a9d6a4d146/TOBIOCJ-2-81_F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/a490c6e18763/TOBIOCJ-2-81_F7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/470c4f10412d/TOBIOCJ-2-81_F8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/ef6a8345c5a9/TOBIOCJ-2-81_F9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/086f2937c4a8/TOBIOCJ-2-81_F10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/605684aaa720/TOBIOCJ-2-81_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/8c74a5d4c016/TOBIOCJ-2-81_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/187f1c55e5a6/TOBIOCJ-2-81_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/b911ef3565fc/TOBIOCJ-2-81_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/4d5a5a7d9f00/TOBIOCJ-2-81_F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/46a9d6a4d146/TOBIOCJ-2-81_F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/a490c6e18763/TOBIOCJ-2-81_F7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/470c4f10412d/TOBIOCJ-2-81_F8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/ef6a8345c5a9/TOBIOCJ-2-81_F9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/2570548/086f2937c4a8/TOBIOCJ-2-81_F10.jpg

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