目的 观察阿魏酸对小鼠外周血象和骨髓造血功能辐射损伤的防护作用,初步探讨阿魏酸的抗辐射作用机制。方法 6~8周ICR小鼠96只,随机数表法分为正常对照组、照射模型组、阳性药(408片)治疗组和阿魏酸10、30、90 mg ·kg-1·d-1治疗组,每组16只。小鼠初次给药后24 h接受3.5 Gy 60Co γ单次全身照射,之后连续7 d给药。其中,每组10只用于观察照射前2 d及照射后3、7、10、15、22 d的外周血象;其余6只用于照射后7 d检测骨髓嗜多染红细胞的微核细胞率、造血祖细胞集落形成能力、以及Thbd和HMGB1蛋白的表达水平。结果 与照射模型组比较,90 mg ·kg-1 ·d-1的阿魏酸可有效提高小鼠3.5 Gy照射后3、10、15、22 d的外周血白细胞数(t=2.267、2.399、1.945、2.828,P〈0.05),显著降低骨髓嗜多染红细胞微核细胞率(t=4.013,P〈0.05),明显提高造血祖细胞红细胞集落生成单位(CFU-E)、红细胞爆裂型集落生成单位(BFU-E)和粒-单细胞集落生成单位(CFU-GM)的集落形成能力(t=2.366、2.953、3.115,P〈0.05),并提高骨髓细胞中Thbd和核内HMGB1蛋白表达水平(t=17.75、23.39,P〈0.01)。结论 阿魏酸可通过调节Thbd和HMGB1蛋白表达,促进小鼠骨髓造血功能辐射损伤修复,加速外周血象恢复。
Objective To observe the effect and the mechanisms of ferulic acid on radiation-induced damage of mice peripheral blood and bone marrow hematopoietic function. Methods Ninety-six mice were randomly divided into sham irradiation group, irradiation group, positive drug group and 10, 30, 90 mg ·kg-1 ·d-1 ferulic acid group, 16 mice per group. Mice were exposed to 3.5 Gy γ-rays 24 h after first drug taken. Then, mice were given drugs for 7 d after irradiation. White blood cells in peripheral blood of 10 mice per group were counted 2 d before irradiation and 3, 7, 10, 15 and 22 days after irradiation. The bone marrow of the other six mice was taken to detect the micronuclei frequency of polychromatic erythrocyte, the hematopoietic progenitor cell colony formation capacity, Thbd and HMGB1 protein expressions in mice bone marrow on the seventh day after irradiation. Results Compared with the irradiation alone group, the treatment of mice with ferulic acid 90 mg ·kg-1 ·d-1 increased the number of white blood cells in peripheral blood at 3, 10, 15 and 22 d after irradiation (t=2.267,2.399,1.945,2.828,P〈0.05). Treatment with mice with ferulic acid 90 mg ·kg-1 ·d-1 decreased the micronuclei rate of erythrocytes in irradiated bone marrow (t=4.013,P〈0.05), increased the clone numbers of CFU-E, BFU-E and CFU-GM of hematopoietic progenitor cells (t=2.366,2.953,3.115,P〈0.05), improved the relative expression of the Thbd protein in bone marrow and the HMGB1 protein in nuclear (t=17.75,23.39,P〈0.01). Conclusions Ferulilc acid could protect the bone marrow hematopoietic of mice exposed to irradiation by regulating the expressions of Thbd and HMGB1 protein, and then accelerate the peripheral cells recovery.