Effects of Qinghuang powder on apoptosis and cycle of bone marrow cells in mice with myelodysplastic syndrome and the mechanism
Objective To investigate the effects of intragastric administration of Qinghuang powder on apoptosis and cycle of bone marrow cells in myelodysplastic syndrome(MDS)mice and the mechanism.Methods The Tg(Vav1-NUP98/HOX D13)G2Apla/J transgenic MDS mouse models were used for sperm extraction and propagation,and 40 model mice were randomly divided into the model group,the low-dose,medium-dose,and high-dose Qinghuang powder groups,and the azacitidine group,with eight mice in each group,and eight C57BL/6J mice were taken as the blank group.Mice in the blank and model groups were given 100 μL of normal saline by gavage once a day;mice in the low-dose,medium-dose,and high-dose Qinghuang powder groups were given 36.4,72.8,and 145.6 mg/kg of Qinghuang powder by gavage once a day;and mice in the azacitidine group were given 100 μL of 1 mg/kg azacitidine by subcutaneous injection in the neck once every 3 days.After 4 weeks of intervention,mice were killed,peripheral blood was collected,and bone mar-row cells were extracted.Blood routine[white blood cells(WBC),red blood cells(RBC),hemoglobin(HGB),and platelets(PLT)]was detected in each group,apoptosis rate and cycle of bone marrow cells were detected by flow cytom-etry,and intracellular DNA methyltransferase 1(DNMT-1),receptor tyrosine kinase(c-KIT),GATA binding protein 1(GATA-1)mRNA,and DNMT-1,c-KIT,and GATA-1 proteins in myeloid cells were detected by Western blotting.Results Compared with the blank group,the model group had lower levels of WBC,RBC,HGB and PLT(all P<0.05),indicating the modeling was successful;WBC,RBC,HGB and PLT were higher in the low-dose and medium-dose Qinghuang powder groups and the azacitidine group(all P<0.05);there were no statistically significant differences in the WBC,RBC,HGB,or PLT among the low-dose,medium-dose,and high-dose Qinghuang powder groups and the azacitidine group(all P>0.05).Compared with the blank group,the apoptosis rate of bone marrow cells in the model group was lower(P<0.05);compared with the model group,the apoptosis rates of bone marrow cells in the low-dose,medium-dose,and high-dose Qinghuang powder groups and the azacitidine group were higher(all P<0.05).Compared with the blank group,the bone marrow cell cycle of the model group changed and the difference was statistically significant(P<0.05);compared with the model group,there were fewer S-phase bone marrow cells and more G1-phase bone marrow cells in the low-dose,medium-dose,and high-dose Qinghuang powder groups and the azacitidine group(all P<0.05).Compared with the blank group,the model group had lower expression levels of DNMT-1,c-KIT and GATA-1 mRNA(all P<0.05);compared with the model group,the low-dose,medium-dose,and high-dose Qinghuang powder groups and the azacitidine group had lower DNMT-1 expression and GATA-1 mRNA expression levels(all P<0.05);and the low-dose,medium-dose Qinghuang powder groups had higher expression levels of c-KIT mRNA(all P<0.05).Compared with the blank group,DNMT-1,c-KIT and GATA-1 protein expression levels were lower in the model group(all P<0.05);com-pared with the model group,the c-KIT protein expression levels were lower,GATA-1 protein expression levels were higher,and DNMT-1 protein expression levels were lower in the low-dose,medium-dose,and high-dose Qinghuang powder groups and the azacitidine group(all P<0.05).Conclusion The intragastric administration of Qinghuang powder can promote apoptosis and block the cell cycle of bone marrow cells in MDS mice,and its mechanism of action may be related to the reg-ulation of the expression of DNMT-1,c-KIT,and GATA-1.
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维普
