Titus Family Clinical Pharmacy and Pharmaceutical Economics and Policy, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Room 530, Los Angeles, CA, 90089, USA,
Cancer Chemother Pharmacol. 2013 Dec;72(6):1235-45. doi: 10.1007/s00280-013-2312-9. Epub 2013 Oct 5.
Angiotensin (1-7) [A(1-7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1-7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and the recovery of circulating formed elements following chemotherapy.
Mice were injected with gemcitabine followed 2 days later with A(1-7). Circulating blood cells and bone marrow progenitors were measured over time.
Combination of A(1-7) with Neupogen (the latter given only 3 days starting at the white blood cell nadir) decreased the amount of Neupogen needed for optimal recovery by 10-fold. The progenitors measured include CFU-GEMM, CFU-GM, CFU-Meg and BFU-E. A(1-7) increased recovery of all progenitors when given alone or in combination with Neupogen above that with Neupogen alone. Combination of A(1-7) with Epogen slightly increased (not significantly) red blood cell concentrations above those achieved by Epogen alone. However, in this model, A(1-7) or A(1-7) in combination with Epogen increased all erythroid progenitors with the largest effect on early erythroid progenitors (immature BFU-E).
Neupogen and Epogen acted synergistically with A(1-7) to increase the concentration of myeloid, megakaryocytic and erythroid progenitor cells in the bone marrow following chemotherapy suggesting that A(1-7)'s multilineage effect on early progenitors in the marrow facilitates proliferation in response to lineage-specific growth factors.
血管紧张素（1-7）[A(1-7)]是肾素-血管紧张素系统的一种生物活性肽，可刺激骨髓祖细胞数量增加，并促进骨髓抑制后的造血恢复。我们评估了 A(1-7)与集落刺激因子、Neupogen 和 Epogen 联合应用对骨髓祖细胞的影响，以及对化疗后循环形成细胞的恢复作用。
给小鼠注射吉西他滨，2 天后给予 A(1-7)。随时间测量循环血细胞和骨髓祖细胞。
A(1-7)与 Neupogen 联合应用（后者仅在白细胞最低点开始的第 3 天给予）可使 Neupogen 达到最佳恢复所需的量减少 10 倍。所测量的祖细胞包括 CFU-GEMM、CFU-GM、CFU-Meg 和 BFU-E。A(1-7)单独或与 Neupogen 联合应用均可增加所有祖细胞的恢复，而不仅仅是 Neupogen 单独应用。A(1-7)与 Epogen 联合应用略微增加（但无统计学意义）红细胞浓度，高于 Epogen 单独应用的水平。然而，在该模型中，A(1-7)或 A(1-7)与 Epogen 联合应用均可增加骨髓中所有红系祖细胞，对早期红系祖细胞（不成熟的 BFU-E）的作用最大。
Neupogen 和 Epogen 与 A(1-7)协同作用，增加化疗后骨髓中髓系、巨核细胞和红系祖细胞的浓度，表明 A(1-7)对骨髓早期祖细胞的多谱系作用促进了对谱系特异性生长因子的增殖反应。
