Résumé
<p><b>OBJECTIVE</b>To investigate the complete blood count, morphological changes, follicular T helper (Tfh) cells and expression of PD-1 in bone marrow and spleen of mice with myelodysplastic syndrome(MDS) and to explore their significance in pathogenesis of MDS.</p><p><b>METHODS</b>The 10 male NUP98-HOXD13 transgenic mice and 10 male homologous wild-type C57BL/6J mice were used for experments. The complete blood count, morphological change of NUP98-HOXD13 transgenic mice and wild-type C57BL/6J were detected by routine methods. The level of Tfh cells and expression of PD-1 in bone marrow and spleen were measured by flow cytometry. The PD-1 mRNA of bone marrow mononuclear cells and spleen cells were analyzed by real-time PCR method.</p><p><b>RESULTS</b>The counts of RBC, neutrophile and platelet in above- mentioned transgenic mice were less than that in wild type C57BL/6J mice. As compared with wild type C57BL/6J mice, the morphology of RBC and platelet in transgenic mice was some abnormal, including bi-nucleated erythrocytes, ringed mucleated neutrophil and erythroblastic islands. The count of Tfh cells in transgenic mice was less than that in wild type mice, but the expression of PD-1 was higher. The expression of BMMNC PD-1 mRNA was obviously higher than that in wild type mice.</p><p><b>CONCLUSION</b>The pancytopenia and dysplasia, decrease of Tfh cells and increase of PD-1 expression have been observed in NUP98-HOXD13 transgenic mice, which may be one of important reasons for promoting malignant clone and leading to impair anti immune respones.</p>
Sujets)
Animaux , Mâle , Souris , Moelle osseuse , Cellules de la moelle osseuse , Cellules cultivées , Cytométrie en flux , Souris de lignée C57BL , Souris transgéniques , Syndromes myélodysplasiques , Pancytopénie , Récepteur-1 de mort cellulaire programmée , Réaction de polymérisation en chaine en temps réel , Lymphocytes T auxiliairesRésumé
Dipeptidyl peptidase-4 (DPP-4) is a protease that cleaves the peptides with alanine, praline, or other selective amino acids at the N-terminal penultimate position. The substrates of DPP-4 include many chemokines, colony-stimulating factors, and interleukins. Recent research has shown that DPP-4 can affect the hematopoietic stem and progenitor cells and transplantation by truncating the granulocyte colony stimulating factor. However, its regulatory effect on DPP-4 and most peptides truncation are still unknown. This review summarizes the recent advances in the DPP-4 research.
Sujets)
Humains , Dipeptidyl peptidase 4 , Physiologie , Hématopoïèse , Transplantation de cellules souches hématopoïétiquesRésumé
The aim of this study was to investigate the effects of D-methionine (D-met) on the hematopoietic system injury in irradiated mice. C57BL/6 mice were divided into control group, irradiated group, 300 mg/kg D-met plus irradiation group and 1000 mg/kg D-met plus irradiation group. The control mice received sham irradiation, and the mice in remainder groups were exposed to 7.5 Gy; 1,4,8 Gy and 1 Gy of (137)Cs γ-ray respectively, were used to detect the survival rate, survival rate of bone marrow cells, WBC and its differential counts as well the colony formation ability in irradiated mice, respectively. The D-met was intraperitoneally injected to mice at 30 min before irradiation. The results showed that 300 and 1000 mg/kd D-met did not obviously enhance the survival rate of mice exposed to 7.5 Gy; the 10(-2),10(-3),10(-4) mol/L D-met significantly increased the survival rate of bone marrow cells in mice exposed to 1,4,8 Gy; 300 and 1000 mg/kg D-met even so increased the WBC count of peripheral blood in mice exposed to 1 Gy, but there was no statistical difference as compared with irradiated alone mice, moreover 300 and 1000 mg/kg D-met could obviously promote the colony formation ability of bone marrow cells in irradiated mice, the CFU-GM count was higher than that in 1 Gy irradiated mice (P < 0.05). It is concluded that the D-met can effectively mitigate the marrow cell injury resulted from irradiation, enhance the survival rate of bone marrow cells in irradiated mice, promote the recovery of hematopoietic function from radiation injury in mice.
Sujets)
Animaux , Souris , Cellules de la moelle osseuse , Effets des rayonnements , Système hématopoïétique , Effets des rayonnements , Numération des leucocytes , Méthionine , Pharmacologie , Souris de lignée C57BL , Lésions radiquesRésumé
<p><b>OBJECTIVE</b>To establish a mouse model of iron overload by intraperitoneal injection of iron dextran and investigate the impact of iron overload on bone marrow hematopoiesis.</p><p><b>METHODS</b>A total of 40 C57BL/6 mice were divided into control group, low-dose iron group (12.5 mg/ml), middle-dose iron group (25 mg/ml), and high-dose iron group (50 mg/ml). The control group received normal saline (0.2 ml), and the rest were injected with intraperitoneal iron dextran every three days for six weeks. Iron overload was confirmed by observing the bone marrow, hepatic, and splenic iron deposits and the bone marrow labile iron pool. In addition, peripheral blood and bone marrow mononuclear cells were counted and the hematopoietic function was assessed.</p><p><b>RESULTS</b>Iron deposits in bone marrow, liver, and spleen were markedly increased in the mouse models. Bone marrow iron was deposited mostly within the matrix with no significant difference in expression of labile iron pool.Compared with control group, the ability of hematopoietic colony-forming in three interventional groups were decreased significantly (P<0.05). Bone marrow mononuclear cells counts showed no significant difference. The amounts of peripheral blood cells (white blood cells, red blood cells, platelets, and hemoglobin) in different iron groups showed no significant difference among these groups;although the platelets were decreased slightly in low-dose iron group [(780.7±39.60)×10(9)/L], middle dose iron group [(676.2±21.43)×10(9)/L], and high-dose iron group [(587.3±19.67)×10(9)/L] when compared with the control group [(926.0±28.23)×10(9)/L], there was no significant difference(P>0.05).</p><p><b>CONCLUSIONS</b>The iron-overloaded mouse model was successfully established by intraperitoneal administration of iron dextran. Iron overload can damage the hepatic, splenic, and bone marrow hematopoietic function, although no significant difference was observed in peripheral blood count.</p>
Sujets)
Animaux , Mâle , Souris , Moelle osseuse , Modèles animaux de maladie humaine , Hématopoïèse , Surcharge en fer , Dextriferron , Toxicité , Souris de lignée C57BL , RateRésumé
This study is to investigate the protective effects of the SB203580 against radiation induced mortality and intestinal injury of mice. A total of 67 male C57BL/6 mice (20.0-22.0 g) were matched according to body weight and randomly assigned to one of three groups: control, total body irradiation exposure (IR, 7.2 Gy) only, and IR (7.2 Gy) + SB203580 (15 mg x kg(-1)). 30 days survival rate was observed in the experiment. In intestinal injury experiment, the expression levels of caspase-3, Ki67, p53 and p-p38 were assayed in the mice intestine crypts. The results showed that the 30 days survival rate was 100% (control), 0 (IR) and 40% (IR+ SB203580), separately. Compared to the IR groups, the positive cells of caspase-3, p53 and p-p38 in crypt cells decreased 33.00%, 21.78% and 34.63%, respectively. The rate of positive cells of Ki67 increased 37.96%. Significant difference was found between all of them (P < 0.01). SB203580 potently protected against radiation-induced lethal and intestinal injury in mice, and it may be a potential radio protector.