Decitabine Enhances the Sensitivity of Leukemia Stem Cell to Allo-NK Cell-Mediated Killing / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the allo-NK cell-mediated killing effect enhanced by decitabine on leukemia stem cells(LSC) and the underlying mechanisms.</p><p><b>METHODS</b>LSC were separated from KG1a cells by using immunomagnetic beads. Allo-NK cells were isolated and purified from PBMC of healthy donors. Cytotoxicity of allo-NK cells against LSC were measured by LDH releasing assay. The apoptosis induced by allo-NK cells in LSC and the expressions of NKG2D ligands including MICA/B and ULBP1-3 on LSC were detected by flow cytometry.</p><p><b>RESULTS</b>The killing rate of allo-NK cells to LSC treated with 10 µmol/L decitabine for 24 hours was significant higher than that to LSC without treatment(60.52%±3.52% vs 22.08%±2.07%, 73.93%±2.33% vs 28. 99%±3.13%, 83.08%±1.32% vs 36.44%±2.40%, respectively)at the effector-target ratios of 5:1, 10:1, 20:1 (P<0.05). At the effector-target ratio of 10:1, decitabine significantly enhanced the apoptosis of LSC induced by allo-NK cells (7.84%±0.34% vs 3.33%±0.64%)(P<0.05). The expressions of NKG2D ligands(MICA/B,ULBP1,ULBP2,ULBP3) on LSC treated with decitabine 10 µmol/L for 24 hours were significantly increased (P<0.05).</p><p><b>CONCLUSION</b>Decitabine may enhance the allo-NK cell-mediated killing effects on LSC by up-regulation of the expressions of NKG2D ligands on LSC.</p>

The effects of safflower injection on lipid peroxidation level and expression of heme oxygenase-1 of the rat liver with hypoxia and hypercapnia / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes of lipid peroxidation level and expression of heme oxygenase-1 of the rat liver with chronic hypoxia and hypercapnia, and the effects of Safflower injection (a compond of Chinese Traditional medicine).</p><p><b>METHODS</b>Thirty male SD rats weighing 180 approximately 220 g were divided into three groups (n=10): control group (N group), chronic hypoxia and hypercapnia for four weeks group(F group), and Safflower injection group (H group). SOD and MDA in liver tissue were measured by spectrophotometric method. And methods Immunohistochemical assay was used to detect the distribution of HO-1 protein. Pathological changes in liver tissues were observed in HE staining section. The mRNA expressions of HO-1 in liver were detected by semi-quantitative RT-PCR.</p><p><b>RESULTS</b>The activity of SOD of the liver in F group were significantly lower than those in N group, and the content of MDA were significantly higher. The activity of SOD of the liver in H group were significantly higher than those in F group, and the content of MDA were significantly lower. In F group there were multiple dispersed immunoreactivity cells in liver. And compared to those in F group, the immunoreactivity cells were significantly decreased in H group. HE staining revealed that there were many hepatocytes with obvious adipose degeneration. Hepatic pathological damage in H group was slighter than that in F group. The expression of HO-1 mRNA of the liver in F group were significantly higher than those in N group (P < 0.01), and those in H group were significantly lower than those in F group (P < 0.01) .</p><p><b>CONCLUSION</b>Chronic hypoxia and hypercapnia increases the level of oxidative stress. Safflower injection have a protective effect, maybe because of the accommodation of the expression of HO-1 of the liver and the elimination of free radicals.</p>

The expression of the early growth responsive gene-1 in acute pulmonary embolism of rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the dynamic changes of Egr-1 expression in the lungs of acute pulmonary embolism of rats by infusion of autoblood thrombs.</p><p><b>METHODS</b>The model of pulmonary embolism by infusion of autoblood thrombs in the pulmonary artery of rats was established and the mean pulmonary arterial pressure was continuously monitored by computer, and the results were evaluated by lung perfusion scan and pathological changes. Expression of Egr-1 proteinum and mRNA were measured by immunohistochemistry and reverse transcription polymerase chain reaction.</p><p><b>RESULTS</b>The mPAP of rats was increased significantly after infusion of autoblood thrombs at the half hour, and reached high level at the second hour, then remained the high level to four hours compared with group control at the same time point (P < 0.01). ECT image was showed significantly filling defect after infusion of autoblood thrombs at the first hour. The infused thromb was witnessed by hematoxylin and eosin stain. In the tracheal epithelium cells, alveolar epithelium cells and vascular smooth muscle cells of embolism rats, Egr-1 protein expression was increased significantly after embolization at the second hour compared with group control at the same time point (P<0.01), and was decreased slowly at the fourth hour. Egr-1 mRNA expression was showed the similar changes.</p><p><b>CONCLUSION</b>Expression of Egr-1 was low level in group control, but increased significantly after infusion of autoblood thromb at the second hour in the specificity of cells, suggesting that Egr-1 expression might be an important link of pathological changes in the acute pulmonary embolism.</p>

Effect of curcumin on pulmonary hypertension and wall collagen of pulmonary arterioles of chronic hypoxic hypercapnic rats / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of curcumin on pulmonary arterial pressure and type I collagen of pulmonary arterioles in pulmonary hypertensive rats induced by chronic hypoxia and hypercapnia.</p><p><b>METHODS</b>Thirty six rats were randomly divided into three groups: normal control group (NC), hypoxic hypercapnic group (HH) and hypoxic hypercapnia + curcumin group (HC). Collagen I in pulmonary arterioles was observed by the technique of immunohistochemistry.</p><p><b>RESULTS</b>(1) The findings from hemodynamics showed that the mPAP in group HH was significantly higher than that in group NC and HC. Differences of mCAP among groups were not significant (P > 0.05). (2) Light microscopy showed the value of WA/TA (vessel wall area/total area), SMC (the density of medial smooth muscle cells) and thickness of pulmonary arterial media smooth cell layer(PAMT) were significantly higher in group HH than group NC (P < 0.01) and group HC (P < 0.01). (3) Electron microscopy showed that structure of the endothelial cells in pulmonary arterioles in group HC was near to normal, and the proliferation of medial smooth muscle cells and collagen fibers in adventitia was much lighter than those of group HH. (4) Expression of collagen I in pulmonary arterioles was significantly higher in group HH than group NC (P < 0.01) and group HC (P < 0.01).</p><p><b>CONCLUSION</b>Curcumin can decrease pulmonary arterial pressure, improve pulmonary vessel remodeling and inhibit the deposition of collagen I in pulmonary arterioles.</p>

Effect of hypoxic hypercapnia on expression of COX-2 mRNA in pulmonary arterioles / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of chronic hypoxic hypercapnia on expression of COX-2 mRNA in pulmonary arterioles.</p><p><b>METHODS</b>SD rats were randomly divided into two groups: control group and hypoxic hypercapnic group. COX-2 mRNA was observed in pulmonary arterioles by the technique of in situ hybridization.</p><p><b>RESULTS</b>mPAP, weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) and COX-2 mRNA in pulmonary arterioles were much higher in rats of hypoxic hypercapnic group than those of control group. Light microscopy showed that vessel smooth muscle cell hypertrophy and vessel cavity straightness were found in hypoxic hypercapnic group.</p><p><b>CONCLUSION</b>Changes of expressions of COX-2 mRNA may regulate hypoxic hypercapnic pulmonary hypertension.</p>

Effect of aspirin on pulmonary hypertension in rat during chronic hypoxia and hypercapnia / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of aspirin on chronic hypoxia and hypercapnic pulmonary hypertension.</p><p><b>METHODS</b>SD rats were randomly divided into normal control group (A), hypoxic hypercapnic group (B), hypoxic hypercapnia + aspirin group (C). The concentration of TXB2 and 6-keto-PGF1alpha in plasma and in lung were detected by the technique of radioimmunology.</p><p><b>RESULTS</b>(1) mPAP was significantly higher in B group than those of A and C group. Differences of mCAP were not significant in three groups. (2) Light microscopy showed that WA/TA (vessel wall area/total area) and PAMT (the thickness of medial smooth cell layer) were significantly higher in B group than those of A and C group. (3) The concentration of TXB2 and 6-keto-PGF1alpha in plasma and lung as well as the ratio of TXB2/6-keto-PGF1alpha were significantly higher in rats of B group than those of A and C group.</p><p><b>CONCLUSION</b>Aspirin may inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling.</p>

Effect and mechanism of chimonin on pulmonary hypertention of chronic hypoxia and hypercapnic rats / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of chimonin on chronic hypoxia and hypercapnic pulmonary hypertension and to explore its mechanism.</p><p><b>METHODS</b>SD rats were randomly divided into normal control group (A), hypoxic hypercapnic group(B), hypoxic hypercapnia + chimonin group (C). HO-1 and HO-1 mRNA was observed in pulmonary arterioles of rats by the technique of immunohistochemistry and in situ hybridization.</p><p><b>RESULTS</b>(1) mPAP was significantly higher in rats of B group than that of A and C group. Differences of mCAP were not significant in three groups. (2) Blood CO concentration was significantly higher in rats of B group than that of A group, it was significantly higher in rats of C group than that of B group. (3) Light microscopy showed that WA/TA (vessel wall area/total area), SMC (the density of medial smooth muscle cell) and PAMT (the thickness of medial smooth cell layer) were significantly higher in rats of B group than those of A and C group. (4) Electron microscopy showed proliferation of medial smooth muscle cells and collagenous fibers of pulmonary arterioles in rats of B group, and chimonin could reverse the changes mentioned above. (5) HO-1 and HO-1 mRNA in pulmonary arterioles was significantly higher in rats of B group than that of A group, they were significantly higher in rats of C group than that of B group.</p><p><b>CONCLUSION</b>Chimonin can inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling by further increasing the expression of HO-1 mRNA.</p>

An experimental study on the regulation of pulmonary arterial remodeling by protein kinase C in chronic hypoxic rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of protein kinase C regulating pulmonary arterial remodeling in chronic hypoxic rats.</p><p><b>METHODS</b>Electron microscope, radioactivity, immunohistochemistry and image analyser were used.</p><p><b>RESULTS</b>(1) Mean pulmonary arterial pressure (mPAP) and weight ratio of RV to LV + S were significantly higher than that of control group (P < 0.01). (2) WA/TA and SMC were significantly higher than that of control group (P < 0.01). Electron microscopy showed the proliferation of smooth muscle cells and the disposition of collagenous fiber in pulmonary arterioles induced by hypoxia. (3) The total, cytosolic, particulate fraction PKC activity and the ratio of particulate fraction to total PKC activity were significantly higher than that of control group (P < 0.01). (4) Expression of PKC, collagen I were significantly higher than that of control group (P < 0.01), the difference of collagen III was not significant between two groups (P > 0.05). (5) There were good correlation between the total, particulate fraction PKC activity, the ratio of particulate fraction to total PKC activity, expression of PKC and SMC, collagen I in pulmonary arterioles.</p><p><b>CONCLUSION</b>The PKC regulates the proliferation of pulmonary artery smooth muscle cells and expression of pulmonary arterial collagen in chronic hypoxic rats, which may play an important role in the pathogenesis of pulmonary hypertension and structural remodeling of pulmonary arteries.</p>