Fedorocko P, Macková N O
Department of Cellular and Molecular Biology, Faculty of Sciences, P.J. Safárik University Kosice, Slovakia.
Int J Immunopharmacol. 1996 May;18(5):329-37. doi: 10.1016/0192-0561(96)00023-9.
We have reported previously [Fedorocko, P., Int. J. Radiat., Biol. 65:465, 1994] that liposomal muramyl tripeptidephosphatidyl ethanolamine (MTP-PE/MLV) given prior to irradiation results in augmented hemopoietic recovery and enhanced animal survival as evidenced by increased pluripotent stem cells (CFU-S) and progenitor cells committed to granulocyte and/or macrophage development (GM-CFC) or white blood cells, neutrophil counts, as well as by survival rates of lethally irradiated mice. In this report the effects of liposomal MTP-PE (radioprotective immunomodulator; 10 mg/kg i.p., 24 h before irradiation) and indomethacin (inhibitor of prostaglandin production; 2 mg/kg i.m., 24 h and 3 h before irradiation) were studied. Both of the agents were administered either alone or in combination. The results included the assessment of preirradiation hemopoietic effects of drugs and postirradiation hemopoietic recovery in terms of bone marrow cellularity, number of bone marrow GM-CFC, endogenous spleen colony formation (endoCFU-S), and the determination of the survival of lethally irradiated mice. Experimental evidence elevated by the increased preirradiation numbers of GM-CFC and hydroxyurea kill of GM-CFC as well as a simultaneous significant diminution in bone marrow cellularity indicated that the beneficial action of the combined treatment could be a consequence of increased cell proliferation in the hemopoietic tissue and mobilization with redistribution of stem cells from bone marrow into the circulation. In the postirradiation period (3-14 days), combined pretreatment of mice accelerated myelopoietic regeneration in the bone marrow compared to treatment with MTP-PE/MLV alone or indomethacin alone. Combined administration of MTP-PE/MLV (10 mg/kg, -24 h, i.p.) and indomethacin (2 mg/kg, -24 h and -3 h, i.m.) to mice, prior to lethal irradiation, exerted an additional radioprotective effect and protected 100% of the C57B1/6 mice.
我们之前已经报道过[费多罗科，P.，《国际辐射生物学》，65:465，1994]，照射前给予脂质体胞壁酰三肽磷脂酰乙醇胺（MTP - PE/MLV）可增强造血恢复并提高动物存活率，这表现为多能干细胞（CFU - S）增加，以及定向于粒细胞和/或巨噬细胞发育的祖细胞（GM - CFC）增加，或者白细胞、中性粒细胞计数增加，同时也表现为受致死剂量照射小鼠的存活率提高。在本报告中，研究了脂质体MTP - PE（辐射防护免疫调节剂；照射前24小时腹腔注射10 mg/kg）和吲哚美辛（前列腺素生成抑制剂；照射前24小时和3小时肌肉注射2 mg/kg）的作用。这两种药物单独或联合给药。结果包括评估药物照射前的造血作用以及照射后骨髓细胞数量、骨髓GM - CFC数量、内源性脾集落形成（endoCFU - S）方面的造血恢复情况，并测定受致死剂量照射小鼠的存活率。照射前GM - CFC数量增加以及GM - CFC经羟基脲杀伤后实验证据增强，同时骨髓细胞数量显著减少，这表明联合治疗的有益作用可能是造血组织中细胞增殖增加以及干细胞从骨髓动员并重新分布到循环中的结果。在照射后时期（3 - 14天），与单独使用MTP - PE/MLV或吲哚美辛治疗相比，联合预处理小鼠可加速骨髓中的髓系再生。在致死照射前，给小鼠联合腹腔注射MTP - PE/MLV（10 mg/kg， - 24小时）和肌肉注射吲哚美辛（2 mg/kg， - 24小时和 - 3小时）具有额外的辐射防护作用，可保护100%的C57B1/6小鼠。
