| [Aims]Observe the significance of the role of the heme oxygenase/carbon monoxide system in hematopoietic regulation for myelodysplastic syndrome and the up-regulation of heme oxygenase/carbon monoxide system’s affection on myelodysplastic syndrome treatment of significance.[Methods]Picked105cases of Myelodysplastic syndrome patients(27cases of patient s with refractory anemia,8cases of patients suffered with refractory anemia w ith ring sideroblasts,26cases of refractory cytopenia with multilineage myelod ysplastic,23patients with the refractory anemia with excess blasts I and21cas es with refractory anemia with excess blasts Ⅱ)who had visited the QiLu hospi tal for diagnosis as the examination group;22healthy people for the control g roup.The bone marrow mononuclear cells and stromal cells were cultured in the appropriate culture systems, semi-quantitative-polymerase chain reaction polymerase chain reaction determination of bone marrow mononuclear cells of HO-1, HO-2expression, application of protein by Western blot method (Western Blotting) the determination of ERk1/2, JNK1/2, of p38MAPK protein and phosphorylation of ERK1/2, JNK1/2and p38MAPK protein expression. The enzyme linked immune--osorbent assay is applied to determination of bone marrow stromal cell culture medium of GM-CSF, SCF and VEGF content. In addition, applied different concentrations of Heme-L-Lysinate intervent bone marrow mononuclear cells and stromal cells in the culture system, then use the above experimental methods detect the expression of indicators in order to observe the function and expression of HO-CO system increases the impact of the MDS patients with bone marrow mononuclear cells and bone marrow stromal cells in the corresponding index.Using SPSS17.0data statistical software to analyze the experimental group and control group experimental results. Using t tests analysis single factor of variance and q test was used to compare the difference from each experimental group, and t’test for heterogeneity of variance.[Results]1HO-1mRNA expression levelsIn MDS-RA, MDS-RARS and MDS-RCMD Group, HO-1mRNA and the normal control group, no significant difference in the MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group, HO-1mRNA expression levels were significantly higher than the normal control group. After the500nmol/4uL HLL intervention, MDS-RA, MDS-RARS, MDS-RCMD, MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group of HO-1mRNA expression level was significantly higher than the corresponding control group.2HO-2mRNA expression levelsIn MDS-RA, MDS-RARS, MDS-RCMD MDS-RAEB Ⅰ and MDS-RAEB Ⅱ groups, HO-2mRNA expression levels between normal control group are not significant different. After the different concentrations of HLL intervention, the MDS-RA,MDS-RARS, MDS-RCMD, the MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group HO-2mRNA expression levels with the corresponding control group, no significant difference.3ERK1/2protein and phosphorylation of ERK1/2protein expression levelsIn MDS-RA, the MDS-RARS, and the MDS-RCMD group, ERK1/2protein and phosphorylation of ERK1/2protein expression levels and the normal control group without obvious differences. In the MDS-RAEB Ⅰ and the MDS-RAEB Ⅱ group, ERK1/2protein and phosphorylation of ERK1/2protein expression levels were significantly higher than the normal control group.After the intervention of different concentrations of HLL, the MDS-RA, MDS-RARS and MDS-RCMD group in LL,5nmol/4uL the HLL and50nmol/4uL,and in500nmol/4uL HLL intervention group,ERK1/2protein and phosphorylation of ERK1/2protein expression levels and the corresponding control group appear no significant difference. MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group,500nmol/4uL HLL Solution intervention group, ERK1/2protein and phosphorylation of ERK1/2protein expression levels were significantly lower than the corresponding control group. LL in the intervention group,5nmol/4uL the HLL in the intervention group,50nmol/4uL the HLL intervention group, ERK1/2protein and phosphorylation of ERK1/2protein expression level with the corresponding control group appear no significant difference.4JNK1/2protein and phosphorylation of JNK1/2protein expression levelsIn MDS-RA, MDS-RARS and the MDS-RCMD group, JNK1/2protein and phosphorylation of JNK1/2protein’s expression level was significantly lower than the normal control group. MDS-RAEB and MDS-with RAEB Ⅱ group, JNK1/2protein and phosphorylation of JNK1,/2protein levels and normal control group not significant different.After the intervention of different concentrations of HLL:the MDS-RA and MDS-RARS, MDS-RCMD group,500nmol/4uL the HLL solution in the in tervention group, JNK1/2protein and phosphorylation of JNK1/2protein expression levels were significantly higher than the corresponding control group, LL,5nmol/4uL HLL,50nmol/4uL the HLL intervention group JNK1/2protein and phosphorylation of JNK1/2protein expression level of the corresponding control group not significant different.5p38MAPK protein and phosphorylated p38MAPK protein expression levelsIn the MDS-RA, MDS-RARS, MDS-RCMD MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group p38MAPK protein and phosphorylated p38MAPK protein were significantly higher than the normal control group.After the intervention of different concentrations of HLL, MDS-RA and MDS-RARS MDS-RCMD MDS-RAEB I and MDS-RAEB II group, p38MAPK protein and phosphorylated p38MAPK protein with500nmol/4uL HLL solution in the intervention group were significantly lower than the corresponding control group. LL in the intervention group the,5nmol/4uL the HLL, intervention group, p38MAPK protein and phosphorylation of50nmol/4uL the HLL intervention group p38MAPK2protein expression level of the corresponding control group no significant difference.6The expression level of caspase-3activityIn the MDS-RA MDS-RARS, MDS-RCMD MDS-RAEBⅠ and MDS-RAEB Ⅱ group of caspase-3activity in the expression levels were significantly higher than the normal control group.After the intervention of different concentrations of HLL, MDS-RA and MDS-RARS MDS-RCMD MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group, the expression levels of caspase-3activity in the HLL solution of500nmol/4uL intervention group was significantly lower than the corresponding control group. LL,5nmol/4uL HLL,50nmol/4uL HLL intervention group, expression levels of caspase-3activity not significant different from the corresponding control group.7SCF expression levelIn the MDS-RA, MDS-RARS, MDS-RCMD MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group SCF secretion was significantly lower than the normal control group.After the intervention of different concentrations HLL:in the MDS-RA and MDS-RARS, MDS-RCMD MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group,500nmol/4uL the HLL solution in the intervention group,SCF secretion was significantly higher than the corresponding control group. LL,5nmol/4uL HLL,50nmol/4uL HLL intervention group, SCF secretion levels had no significant difference from the corresponding control group.8GM-CSF expression levelsIn the MDS-RA and MDS-RARS, MDS-RCMD MDS-with RAEB Ⅰ and MDS with RAEB Ⅱ group of GM-CSF secretion was significantly lower than the normal control group.After the intervention of different concentrations HLL:In the MDS-RA MDS-RARS, MDS-RCMD MDS-RAEB Ⅰ and MDS-RAEB Ⅱ group,500nmol/4uL the HLL solution in the intervention group the GM-CSF, secretion was significantly higher than the corresponding control group. While LL,5nmol/4uL HLL,50nmol/4uL,GM-CSF secretion had no significant difference with the corresponding control group.9VEGF expression levelIn the MDS-RA and MDS-RARS, MDS-RCMD group of VEGF levels with the normal control group, no significant difference in the MDS-with RAEB Ⅰ MDS-with RAEB Ⅱ group VEGF secretion levels were significantly higher than the corresponding control group.After the intervention of different concentrations HLL:In MDS-RA and MDS-RARS, MDS-RCMD MDS-with RAEB Ⅰ and MDS with RAEB Ⅱ group, the500nmol/4uL HLL the intervention group’s VEGF secretion level was significantly lower than the corresponding control group. LL,5nmol/4uL HLL and50nmol/4uL HLL intervention group’s VEGF secretion level had no significant difference with the corresponding control group.[Conclusion]HO/CO system can affect several signaling pathways, which plays an important role in the regulation of hematopoiesis. Its regulatory role MDS hematopoietic system can help restore normal hematopoietic function. Function increase of the HO/CO system has a general role in cell protection not only on the normal hematopoietic cells in MDS patients and hematopoietic stromal cells can also be excessive apoptosis of normal hematopoietic cells in MDS bone marrow, bone marrow matrix in the SCF, GM-CSF reduced secretion of VEGF generate excessive characteristic pathological mechanisms appropriate protection of normal hematopoietic cells and marrow stromal cells.HLL could increase the expression of HO/CO system. The state of in vitro cell culture,500nmol/4uL HLL solution can reduce the MDS of the bone marrow of patients with early hematopoietic cell apoptosis, increasing the secretion of bone marrow stromal cells on SCF, GM-CSF, and can inhibit the MDS-with RAEB Ⅰ MDS-with RAEB Ⅱ patients the secretion of VEGF in the bone marrow stromal myelodysplastic syndrome with therapeutic value. With500nmol/4uL HLL solution cultured in vitro can reduce the MDS bone marrow of early hematopoietic cell apoptosis and increased bone marrow stromal cells of the SCF and GM-CSF secretion, and inhibit the overwhelm VEGF secretion in MDS-RAEB Ⅰ and MDS-RAEB Ⅱ patients with bone marrow stroma. All the information above suggests up regulate the HO/CO system is a valuable therapy for myelodysplastic syndrome. |
PDF Full Text Request