沙棘黄酮对辐射损伤小鼠造血系统的保护作用及其机制

Protective role of hippophae rhamnoides flavone in hematopoietic system of radiation-induced damage mice and its mechanism

目的观察沙棘黄酮对辐射损伤小鼠造血调控因子的调节作用和对骨髓单个核细胞(BMNCs)细胞周期的影响。方法BALB/c小鼠随机分为空白对照组、放射对照组和给药组。建立接受4 Gy直线加速器一次性照射的辐射损伤小鼠模型。空白对照组给予假照射,其他两组受试小鼠依次接受直线加速器单次全身照射(4.0 Gy,3.2 Gy/min,焦点距小鼠约100 cm,照射时间1.25 min),给药组在照射造模当天开始灌胃给予沙棘黄酮混悬液,连续灌胃至造模后14 d。造模后3 d和14 d分别检测小鼠血清造血调控因子G-CSF、TPO、IL-1β和TNF-α水平,并观察BMNCs细胞周期和凋亡率的变化。结果与空白对照组相比,放射对照组小鼠G-CSF、TPO和IL-1β水平明显升高,TNF-α水平明显升高(均P<0.05);BMNCs细胞周期检测G0/G1期细胞比例显著增加,S期细胞比例显著减少,细胞凋亡率明显增多(均P<0.05)。与放射对照组相比,给药组小鼠G-CSF、TPO和IL-1β水平均明升高,TNF-α水平明显降低(均P<0.05);BMNCs细胞周期检测G0/G1期细胞比例显著降低,S期细胞比例显著增多,细胞凋亡率明显减少(均P<0.05)。造模后14 d与造模后3 d比较,给药组小鼠G-CSF、TPO和IL-1β水平显著升高,TNF-α水平明显下降,BMNCs细胞周期检测G0/G1期细胞比例显著上升,细胞凋亡率明显降低(均P<0.05)。结论沙棘黄酮可能通过上调造血调控因子G-CSF、TPO、IL-1β水平,下调TNF-α水平,降低G0/G1期细胞比例以及细胞凋亡率,促进辐射损伤小鼠造血功能的恢复。

Objective To observe the regulatory effect of seabuckthorn flavonoids on hematopoietic regulatory factors in radiation-induced damage mice and the cell cycle of bone marrow mononuclear cells(BMNCs).Methods Mice were treated with 4 Gy linear accelerator for one-time irradiation to establish a radiation injury mouse model.BALB/c mice were randomly divided into blank control group,radiation control group and seabuckthorn flavonoids group.The mice were given sham irradiation in blank control group,the mice in the other two groups received a single whole body irradiation(4.0 Gy,3.2 Gy/min,the focus far away from mouse about 100 cm,irradiation for 1.25 min)in sequence,and the mice in seabuckthorn flavonoids group were given seabuckthorn flavonoids suspension by gavage from the day of radiation modeling to 14 d after modeling.The serum levels of hematopoietic regulatory factors G-CSF,TPO,IL-1βand TNF-αwere detected 3 d and 14 d after modeling,and the changes of cell cycle and the apoptosis rate of BMNCs were observed.Results Compared with blank control group,the levels of G-CSF,TPO,IL-1βand TNF-αwere significantly increased in radiation control group(all P<0.05),the percentage of G0/G1 cells was significantly increased,the proportion of S phase cells was significantly reduced,and the apoptosis rate was significantly increased(all P<0.05).Compared with radiation control group,the levels of G-CSF,TPO and IL-1βwere significantly increased in seabuckthorn flavonoids group(P<0.05),the level of TNF-αwas significantly decreased(P<0.05),the percentage of G0/G1 cells was significantly decreased,the percentage of S phase cells was significantly increased,and the apoptosis rate was significantly reduced(all P<0.05).Compared with 3 d after modeling,the levels of G-CSF,TPO and IL-1βwere significantly increased in seabuckthorn flavonoids group at 14 d after modeling,and the levels of TNF-αwere significantly decreased,the percentage of cells in G0/G1 phase of BMNC cell cycle was significantly increased,and the rate of cell apoptosis was significantly reduced(P<0.05).Conclusion Seabuckthorn flavonoids can promote the hematopoiesis in radiation-injured mice by up-regulating the levels of hematopoietic regulatory factors G-CSF,TPO,IL-1βand down-regulating the level of TNF-αin radiation-injured mice,and reducing the percentage of G0/G1 cells and the rate of apoptosis.