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AIM:To observe the effects of panaxadiol saponins(PDS)on up-regulation of MAPK/ERK signal pathway in bone marrow cells and increase in regulatory T(Treg)cells in spleen tissue of aplastic anemia(AA)mice,and to explore the mechanisms.METHODS:For preparation of immune-mediated AA model,BALB/c mice were exposed to sublethal dose(5.0 Gy)of [60Co]-γradiation, followed by transplantation of lymphocytes from DBA /2 donor mice. BALB/c mice(n=60)were randomly divided into 6 groups,including normal mouse group,AA model group,PDS treat-ment groups at low,medium and high doses,and cyclosporine group as positive control.PDS and cyclosporine were given by gavage for 14 d.The peripheral blood cell counts and bone marrow pathological examination were tested.The protein levels of MEK1/2,p-MEK1/2,ERK1/2 and p-ERK1/2 in the bone marrow cells were analyzed by Western blot and im-munohistochemistry experiment.Flow cytometry was used to detect the proportion of Treg cells in spleen tissue of each group.RESULTS:The peripheral blood cell counts were significantly decreased in AA mouse group as compared with nor -mal mouse group(P<0.05).The bone marrow sections showed markedly inhibition status of hematopoiesis and the de -crease in cellularity.In response to PDS treatment,the peripheral blood cell counts and Treg cells in the spleen tissues of AA mouse treated with PDS were significantly increased in a dose-dependent manner(P<0.05).Treatment with PDS at medium and high doses up-regulated the protein levels of MEK1/2,p-MEK1/2,ERK1/2 and p-ERK1/2 in the bone mar-row of AA mice(P<0.05).CONCLUSION:PDS is effective to enhance recovery of hematopoietic function in AA mice. This effect may be related to up-regulating multiple protein kinases of MAPK/ERK signal pathway in the bone marrow cells of AA mice.In addition,PDS has an impact on immune function of AA mice.
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<p><b>OBJECTIVE</b>To explore the mechamisms of mitochondria-mediated pathway in apoptosis of platelets resulted from in immune induced bone marrow failure.</p><p><b>METHODS</b>Thirty C57BL/6 mice were randomly divided into 3 groups (10 mice in each group): normal group, model group, cyclosporine A(CsA) group. Mouse model of immune bone marrow failure were established. After mouse model was successfully established, the mice in normal group and model group were given saline orally, the mice in CsA group was treated with CsA orally. Blood routine examination of mice in each group was performed by automatic blood cell analyzer; the mitochondrial membrane potential(ΔΨm), cytochrome C(Cyt C), phosphatidylserine (PS), Cawere measured by flow cytometry; expression of BAX, BAK, caspase-3, caspase-8, caspase-9 was detected by using Western blot method, the changes of bone marrow platelet ultrastructure were observed under transmission electron microscope.</p><p><b>RESULTS</b>Compared with normal group, the platelet count of model group decreased significantly, while the level of ΔΨm, caspase-3, caspase-8, caspase-9 significantly decreased, the level of Cyt C, PS, Ca, BAX, BAK increased significantly (P<0.05). Compared with the model group, the platelet count of CsA group increased obviously, while the level of ΔΨm, caspase-3, caspase-8, caspase-9 of CsA group increased significantly, the level of Cyt C, PS, Ca, BAX, BAK of CsA group decreased significantly (P<0.05). Electron microscopy showed that compared with the model group, platelet damage in CsA group were alleviated.</p><p><b>CONCLUSION</b>mitochondrial pathway plays an important role in the reduction of platelet resulted from immune bone marrow failure.</p>