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目的:基于Notch4和Delta4探讨当归补血汤(Danggui Buxue Decoction,DBD)协同肌源性干细胞(Musclederived stem cells,MDSCs)向造血方向调控的作用机制。方法:将雌性昆明小鼠随机分成6组,分别为照射模型组、骨髓移植组、MDSCs移植组、等效剂量DBD预处理+MDSCs组(给药1组)、3倍DBD预处理+MDSCs组(给药2组)和5倍DBD预处理+MDSCs移植组(给药3组)。照射前各组分别给予生理盐水和不同剂量DBD灌胃1周,经8Gy~(137)Cs-γ射线照射后,尾静脉分别移植骨髓细胞和MDSCs。用real-time PCR检测3周末时小鼠骨髓中CD34、Notch4和Delta4 mRNA表达量。结果:与照射模型组比,干预组中CD34 mRNA上调(P<0.05),且以给药3组上调幅度最大;Notch4 mRNA下调(P<0.05),且给药1组下调幅度最大;除骨髓移植组外,其余各组Delta4 mRNA均上调(P<0.05),且给药3组上调幅度最大。结论:当归补血汤协同肌源性干细胞移植能促进受照射小鼠造血重建,且5倍当归补血汤协同MDSCs移植效果最佳。Notch4和Delta4在骨髓造血干细胞移植和MDSCs移植中的作用不同,其促进骨髓造血干细胞、MDSCs向造血细胞分化的具体调控机制尚待深入探索。
OBJECTIVE: To explore the mechanism of Danggui Buxue Decoction (DBD) cooperating with Musclederived stem cells (MDSCs) in the hematopoietic regulation based on Notch4 and Delta4. Methods: Female Kunming mice were randomly divided into 6 groups: irradiation group, bone marrow transplantation group, MDSCs transplantation group, DBD pretreatment + MDSCs group (administration group 1), 3 times DBD pretreatment + MDSCs group (Administration 2 groups) and 5 times DBD pretreatment + MDSCs transplantation group (administration 3 groups). Before irradiation, the rats in each group were given normal saline and different dosages of DBD for one week, respectively. After being irradiated with 8Gy ~ (137) Cs-γ ray, bone marrow cells and MDSCs were transplanted into tail vein respectively. Real-time PCR was used to detect the expression of CD34, Notch4 and Delta4 mRNA in the bone marrow of mice at 3 weeks. Results: Compared with the irradiation group, CD34 mRNA was up-regulated in the intervention group (P <0.05), and the up-regulation rate was the highest in the three groups; Notch4 mRNA was down-regulated Delta4 mRNA was up-regulated in the other groups (P <0.05) except for the transplantation group, and the up-regulation was the highest in the three groups. Conclusion: Dangguibuxuetang combined with myogenic stem cell transplantation can promote the hematopoietic reconstitution in irradiated mice, and 5 times the Dangguibuxuetang synergistic MDSCs transplantation best. The roles of Notch4 and Delta4 in bone marrow hematopoietic stem cell transplantation and MDSCs transplantation are different. The specific regulation mechanism of Notch4 and Delta4 that promote the differentiation of bone marrow hematopoietic stem cells and MDSCs into hematopoietic cells remains to be further explored.