机构地区:[1]军事医学科学院放射与辐射医学研究所,北京100850
出 处:《癌变.畸变.突变》2014年第6期434-437,440,共5页Carcinogenesis,Teratogenesis & Mutagenesis
基 金:全军"十二五"医学科研重点课题(BWS11J009);国家自然科学基金(30900381)
摘 要:目的:观察曲酸(KA)对4 Gy射线照射所致小鼠Treg/Th17细胞比例失衡的影响,以期为KA的辐射免疫损伤防护机制研究提供新思路。方法:C57BL/6雄性小鼠随机分为对照组、照射组、KA低剂量组和KA高剂量组。KA低、高剂量组小鼠分别于照射前27 h皮下注射75、300 mg/kg KA。照射组及KA低、高剂量组小鼠接受4 Gyγ射线一次性全身照射,对照组行假照射。照射后检测外周血白细胞(WBC)数量、脾脏/胸腺指数及脾脏调节性T细胞(Treg细胞)和Th17细胞比例的改变。结果:与对照组比较,4 Gyγ射线照射后,小鼠外周血WBC计数显著降低(<0.05或P<0.01),KA高剂量组WBC计数至照后19 d恢复正常,而照射组及KA低剂量未恢复。γ射线照射后,照射组及KA低、高剂量组小鼠胸腺及脾脏指数均显著降低(P均<0.01),但KA高剂量组的胸腺及脾脏指数明显高于照射组(P均<0.01)。照后4 d,照射组与KA高剂量组脾脏Treg细胞比例显著高于对照组(P均<0.01)。照射组Th17细胞比例亦显著增高,而KA高剂量组Th17比例却显著低于照射组(P<0.05),使得Treg/Th17比值在照后4 d明显增高,导致Treg/Th17平衡向Treg方向明显偏移。结论:适当剂量的KA预防给药能明显减轻γ射线照射所致的免疫损伤,并能抑制照射所致的Th17细胞比例增高,导致Treg/Th17平衡向Treg细胞方向偏移。表明KA可抑制照射所引起的炎性反应,从而减轻机体的炎症性损伤,发挥有效的保护作用。OBJECTIVE:To observe the effect of kojic acid (KA) on the disequilibrium of Treg/Th17 induced by 4 Gyγray irradiation,in order to provide new ideas for the study of protective mechanisms of KA on immune injury induced by radiation. METHODS:Male C57BL/6 mice were randomly divided into control group,radiation group,KA low group and KA high group. Mice in KA low,high group were treated with 75 or 300 mg/kg KA subcutaneously,respectively,27 h before irradiation. Mice in radiation group and KA low,high group received 4 Gyγray for whole body irradiation(WBI) and control group received sham irradiation. After WBI,peripheral blood count,spleen/thymus index and percentage of splenic regulatory T cells (Tregs) and Th17 cells were measured. RESULTS:Peripheral WBC count in mice was significantly decreased after 4 Gyγray irradiation. WBC count in KA high group recovered at 19 d post irradiation,while that in radiation and KA low groups did not recover. Mouse thymus and spleen index in radiation and KA low,high groups were significantly decreased post radiation,but thymus and spleen index in KA high group was significantly higher than that of radiation group. The proportion of splenic Tregs in radiation group and KA high group was significantly higher than that of control group at 4 d post irradiation. The proportion of Th17 in radiation group increased significantly,but the proportion of Th17 in KA high group did not change markedly,and was much lower than that of radiation group. Because of no increase of Th17 in KA high group,the ratio of Treg/Th17 was significantly raised at 4 d post irradiation,leading to an abvious shift towards Tregs. CONCLUSION:KA could significantly alleviate immune injury and inhibit the rise of Th17 induced by γ ray irradiation,causing Treg/Th17 towards to Tregs. These indicated that KA could play a protective role by inhibiting the inflammatory induced by irradiation,thus reduce the damage effect of inflammatory responses in the body.
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