褪黑素对小鼠淋巴细胞电离辐射损伤的防护作用

目的 探讨褪黑素(MLT)对小鼠淋巴细胞电离辐射损伤的防护作用及其机制。方法 采用流式细胞术和荧光分光光度法在离体和整体条件下分别检测小鼠淋巴细胞凋亡小体百分率和DNA裂解率。在此基础上,腹腔注射MLT,观察2 Gy X射线全身照射后24 h小鼠胸腺、脾脏淋巴细胞数量及胸腺细胞³H-TdR掺入率和Con A、LPS诱导的脾T、B淋巴细胞转化率的变化。结果 离体研究中,小鼠胸腺和脾脏淋巴细胞体外接受0.5~6.0 Gy照射后,凋亡小体百分率、DNA裂解率均呈剂量依赖性增加,而照射前预先加入2 mmol/L MLT,细胞凋亡小体百分率、DNA裂解率与单纯照射组比较均显著降低。整体研究中,2Gy全身照射前腹腔注射MLT,小鼠胸腺和脾脏淋巴细胞凋亡小体百分率和DNA裂解率显著低于单纯照射组,接近或低于假照水平,MLT剂量在0.1~2.5 mg/kg范围内均有作用,但无明显剂量依赖性。小鼠胸腺、脾脏淋巴细胞数量、胸腺细胞³H-TdR掺入率及有丝分裂原诱导的脾脏T、B淋巴细胞转化率在2 Gy全身照射后均显著低于假照组(P <0.001)。0.5~10 mg/kgMLT预先腹腔注射,胸腺、脾脏淋巴细胞数显著高于0 mg/kg体重组(单纯照射),其中0.5 mg/kg体重组增高最显著;胸腺细胞³H-TdR掺入率显著增高(P <0.01或P <0.001),以0.5 mg/kg体重组增高最显著;Con A诱导的T细胞转化率显著增高,也以0.5 mg/kg体重组为著;LPS诱导的B细胞转化率增高,以10mg/kg体重组最显著。结论 MLT在体内和体外均可减轻电离辐射诱导的小鼠淋巴细胞损伤,对免疫功能具有保护作用。

Protective Effects of Melatonin on Damage of Lymphocytes in Mice Induced by Ionizing Radiation

Objective To explore the protective effects of melatonin (MLT) on the damage of lymphocytes in mice induced by ionizing radiation and its mechanism.Methods The percentages of apoptotic bodies and the DNA lytic rates of thymocytes and splenocytes in mice in vitro and in vivo were detected with flow cytometry and fluorospectrophotometry, respectively.MLT was given to mice through intraperitoneal injection 60 min before the whole-body irradiation with 2 Gy X-rays.Twenty four hours after irradiation, the number of thymocytes and splenocytes, ³H-TdR incorporative rate (HTIR) of thymocytes and T and B lymphocyte transfo rming rates (TLTR and BLTR) induced by Con A and LPS were observed.Results The apoptosis of mouse thymocytes and splenocytes in vitro increased with significant dose-dependence in 0.5~6.0 Gy irradiation.When MLT of 2 mmol/L was added into thymocytes or splenocytes in vitro before irradiation with 0.5~6.0 Gy, the percentages of apoptotic bodies and the DNA lytic rates all decreased significantly as compared with those in the irradiation group.When MLT was injected into intraperitonium in mice 60 min befo re the whole-body irradiation with 2 Gy, the percentages of apoptotic bodies and the DNA lytic rates were significantly lower than those in the irradiation group, and near or lower than those in the sham-irradiation group.MLT of 0.1~2.5 mg/kg decreased the ly mphocyte apoptosis, but without significant dose-dependence.The number of thymocytes and splenocytes, HTIR, TLTR and BLTR were all significantly lower than those in sham-irradiation group 24 h after irradiation (P <0.001).When MLT of 0.5~10 mg/kg BW was given before irradiation, the number of thymocytes and splenocytes was significantly higher than that in 0 mg/kg BW group (simple irradiation, P <0.01), and the effect of MLT of 0.5 mg/kg BW was more obvious;HTIR of thymocytes also increased significantly, and effect of 0.5 mg/kg BW was more obvious;TLTR induced by Con A in 0.5 mg/kg BW group increased more significantly, while BLTR in 10 mg/kg BW group increased more significantly.Conclusion MLT can decrease the damage of ly mphocytes in mice induced by ionizing radiation in vitro and in vivo, and has the protective effect on immune functions.