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

代谢增强药物、干扰素和白细胞介素2对受辐射小鼠损伤淋巴细胞恢复的增强作用。

• 批准号: 63480519
• 负责人: MIYOSHI Takeyoshi
• 金额: $ 0.96万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480519/
• 关键词: Radiation damage; lymphocyte; Bone marrow cell (BMC); Cepharanthin; Meclofenoxate hydrochride; Citicoline; Cytochrome C; Interleukin-2 (IL-2); White blood cell (WBC); CFU-S; CFU-C; チトクロームC; IFN; IL-2; 細胞膜荷電; リンパ球幼若化反応; NK活性

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

本文通过测定辐射损伤后骨髓细胞（MNC）、外周血白色细胞（WBC）、粒细胞和淋巴细胞的计数，研究了激活生理呼吸系统的药物对辐射损伤修复过程中细胞免疫状态的影响。CFU-S数量（集落形成单位-脾）和NK细胞活性。千金藤素（细胞膜修饰药物）和细胞色素C（一种激活线粒体电子传递系统ATP生成的药物）。在低剂量照射的情况下，单独或联合应用对BMC和WBC的恢复均有一定的效果。然而，在辐射剂量增加的情况下，必须减少药物剂量才能产生效果。在高剂量辐射下，每种药物及其组合均显示出负面影响，并对细胞造成一定的损害。 ...更多信息 白细胞虽能轻微增加BMC的修复作用。为了补充这一结果，并激活产生ATP的代谢系统的所有过程，在头孢黄质和细胞色素C的组合中引入了盐酸甲哌沙酯（一种碳水化合物代谢的激活药物）和胞磷胆碱（一种激活脂质代谢和卵磷脂合成的药物）。四种药物联合应用不能促进大剂量辐射小鼠白细胞的恢复，但对白细胞无明显的毒副作用。在这种情况下，BMC的恢复略有增强。这些结果表明，即使BMC可以从辐射损伤中修复，但仍有辐射损伤残留阻碍BMC向外周血WBC的分化和成熟。在淋巴细胞研究中，细胞色素C对受照小鼠NK细胞活性和T细胞功能有轻度的增强作用，而细胞免疫功能增强剂干扰素（Interferon）对大剂量照射小鼠WBC和BMC的恢复无明显促进作用，故不能用于治疗。调节细胞免疫状态的药物之一，在大剂量照射时不能促进白细胞的恢复，在单纯照射时也有同样的效果，但外周血白细胞有较好的成熟度，BMC有明显的提高，但与预期相反，外周血白细胞增多的主要成分是中性粒细胞，而不是淋巴细胞。由于IL-2与比先前实验中更低剂量的药物组合使用，这些药物联合应用能显著促进大剂量辐射损伤小鼠WBC和BMC的修复，提示应用IL-2等免疫激活剂对辐射严重损伤小鼠WBC和BMC的修复是非常有效的2与产生ATP的呼吸代谢系统的激活剂结合。但是，人们认为，加强淋巴细胞辐射损伤修复的新药物还有待于进一步研究。少

项目成果

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