Enhancement effects of augmentation drugs of metabolism, interferon and interleukin-2 on recovery of lymphocyte from damage in irradiated mice.

本文通过测定辐照小鼠骨髓细胞（MNC）、外周血白细胞（WBC）、粒细胞和淋巴细胞的计数、CFU-S （Colony Formation unit -脾脏）数量和nk细胞活性，研究了药物激活生理呼吸系统和细胞免疫状态的作用，探讨了辐射损伤后骨髓细胞（MNC）和外周血白细胞（WBC）、粒细胞和淋巴细胞的修复过程。首先，在辐照小鼠中研究了Cepharanthin（一种细胞膜修饰药物）和Cytochrome C（一种激活线粒体电子传递系统atp生成的药物）。在低剂量照射下，单独使用或联合使用均能有效恢复BMC和WBC。但是，在辐射剂量增加的情况下，必须减少药物的剂量才能产生效果。在高剂量照射下，单药及联合用药虽能轻微增强BMC的修复功能，但均表现出负作用，对白细胞有一定损害。为了补充这一结果并激活产生ATP的代谢系统的所有过程，在Cepharanthin和Cytochrome c的组合中引入了碳水化合物代谢激活药物盐酸甲氯芬酸盐和胞胆碱（激活脂质代谢和卵磷脂合成的药物），这四种药物联合使用不能促进WBC的恢复，但对高剂量辐射小鼠的WBC没有负面和毒性作用。在这种情况下，BMC的恢复略有增强。这些结果表明，即使BMC在辐射损伤后可以修复，但仍存在辐射损伤的残留，阻碍了BMC向外周白细胞的分化和成熟。在淋巴细胞的研究中，细胞色素C能轻微增强辐照小鼠nk细胞活性和t细胞功能。另一方面，作为细胞免疫功能增强药物之一的干扰素不能同时促进高剂量辐射小鼠白细胞和BMC的恢复。因此，这种药物是不可用的。白细胞介素-2 （IL-2）是调节细胞免疫状态的药物之一，在高剂量辐射下不能促进白细胞的恢复，在单独辐射下效果相同，但外周白细胞表现出良好的成熟图，BMC明显增强。但与预期相反，外周血白细胞增加的主要化合物是中性粒细胞，而不是淋巴细胞。由于IL-2与较低剂量的药物联合使用，这些药物联合使用均能显著增强高剂量辐射小鼠白细胞和BMC的修复。这些结果表明，IL-2等免疫激活剂联合呼吸代谢系统产生ATP的激活剂对严重辐射损伤的白细胞和BMC的修复是非常有效的。但增强淋巴细胞对放射损伤的修复能力的新药有待进一步研究。少

On the process of the repair of bone marrow cells (MNC) and peripheral white blood cells (WBC), granulocytes and lymphocytes, from radiation damage, the effects of drugs activating the physiological respiration system and immunological status of cells were studied in this report by using the measuring of counts of WBC,granulocytes and lymphocytes, numbers of CFU-S (Colony Formation Unit-Spleen) and NK-cell activity in irradiated mice.At the beginning, Cepharanthin(a modification drug of cell membrance) and Cytochrome C(a activating drug ATP-production of electron-transfer-system in mitochondria) were studied in irradiated mice. Each alone of them and the combination of them were effective on the recovery of BMC and WBC in the case of lower dose of radiation. However, the dose of drugs had to be reduced to have effects in the case of increasing radiation doses. And at the high dose of radiation, both each drugs and the combination of them showed negative effects and gave some damage to … More WBC even though they could augment slightly the reparation of BMC. To supplement this results and to activate all process of metabolic system producing ATP, Meclofenoxate hydrochloride (a activating drug of carbohydrate metabolism) and Citicoline (a drug activating lipid metabolism and synthesis of Lecitine) were introduces in the combination of Cepharanthin and Cytochrome C. The combination of four these drugs could not enhance the recovery of WBC but did not show negative and toxic effects to WBC in mice irradiated with high dose of radiation. BMC's recovery were slightly enhanced in this case. These results indicted that there were remains of radiation damage retarding the differentiation and maturation to peripheral WBC from BMC even if BMC could be repaired from radiation damage. In studies of lymphocyte, Cytochrome C could augment slightly NK-cell activity and T-cell function in irradiated mice.On the other hand, Interferon, one of augmentation drugs of immunological function in cells, could not enhance the recovery of both WBC and BMC in mice irradiated with high dose of radiation.Therefore, this drug was not available for purpose.Interleukin-2 ( IL-2 ), one of drugs regulating immunostatus of cells, could not enhance the recovery of WBC in the case of high dose radiation and showed the same results in the case of radiation alone but the peripheral WBC showed the good figure of maturation, and BMC were remarkably enhanced.But on the contrary of expectation, the main compounds of WBC increasing in peripheral blood was neutrophils and was not lymphocytes. As IL-2 was used in combination with for drugs of lower dose than in previous experiments, the combination of all these drugs could enhance remarkably the reparation of both WBC and BMC in mice irradiated with high dose of radiation.These results indicated that it was very available for reparation of WBC and BMC from the severe damage of radiation to administer immuno-activators like IL-2 combined with activators of the respiratory metabolic system producing ATP. But it was thought that the new drugs enhancing the reparation of lymphocytes from radiation damage have to be studied in future. Less