Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into h...Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group（ 10％ O2, 8h/d） and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling（ TUNEL） technique was used to detect nucleosomal DNA fragmentation of apoptotic cells. In situ hybridization and RT- PCR were used to detect the expression level of bcl- 2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT- PCR, we found the expression of bcl- 2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bcl- 2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.展开更多
Macrophage cells play an important role in the initiation and regulation of the immune response. All-trans retinoic acid (ATRA) and its natural and synthetic analogs (retinoids) affect a large number of biological pro...Macrophage cells play an important role in the initiation and regulation of the immune response. All-trans retinoic acid (ATRA) and its natural and synthetic analogs (retinoids) affect a large number of biological processes.Recently , retinoids have been shown promise in the therapy and prevention of various cancers. However, many interesting questions related to the activities of retinoids remain to be answered: (Ⅰ) Molecular mechanisms by which retinoids exert their effects; (Ⅱ) why the clinical uses of retinoids give undesirable side effects of varying severity with a higher freqllency of blood system symptoms; (Ⅲ)little is known for its impacts on macrophage cells etc. We set up this experiment, therefore, to examine the apoptosis of ATRA on macrophage Ana-1 cell line. Apoptosis of the cells was quantitated, after staining cells with propidium iodide (PI), by both accounting nuclear condensation and flow cytometry. When the cells were treated with ATRA at or higher than 1 μM for more than 24 h, significant amount of the apoptotic cells was observed. Induction of apoptosis of Ana-1 cells by ATRA was in time- and dose-dependent manners, exhibiting the similar pattern as the apoptosis induced by actinomycin D (ACTD). ATRA treatment of Ana-1 cells also caused the changes of the mRNA levels of apoptosis-associated gene bcl-2, as detected by Northern blot analysis. The temporal changes of bcl-2 expression by ATRA was also parallel to that by ACTD. In conclusion,ATRA can induce apoptosis in macrophage cells, which may be helpful in understanding of immunological functions retinoids.展开更多
文摘Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group（ 10％ O2, 8h/d） and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling（ TUNEL） technique was used to detect nucleosomal DNA fragmentation of apoptotic cells. In situ hybridization and RT- PCR were used to detect the expression level of bcl- 2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT- PCR, we found the expression of bcl- 2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bcl- 2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.
文摘Macrophage cells play an important role in the initiation and regulation of the immune response. All-trans retinoic acid (ATRA) and its natural and synthetic analogs (retinoids) affect a large number of biological processes.Recently , retinoids have been shown promise in the therapy and prevention of various cancers. However, many interesting questions related to the activities of retinoids remain to be answered: (Ⅰ) Molecular mechanisms by which retinoids exert their effects; (Ⅱ) why the clinical uses of retinoids give undesirable side effects of varying severity with a higher freqllency of blood system symptoms; (Ⅲ)little is known for its impacts on macrophage cells etc. We set up this experiment, therefore, to examine the apoptosis of ATRA on macrophage Ana-1 cell line. Apoptosis of the cells was quantitated, after staining cells with propidium iodide (PI), by both accounting nuclear condensation and flow cytometry. When the cells were treated with ATRA at or higher than 1 μM for more than 24 h, significant amount of the apoptotic cells was observed. Induction of apoptosis of Ana-1 cells by ATRA was in time- and dose-dependent manners, exhibiting the similar pattern as the apoptosis induced by actinomycin D (ACTD). ATRA treatment of Ana-1 cells also caused the changes of the mRNA levels of apoptosis-associated gene bcl-2, as detected by Northern blot analysis. The temporal changes of bcl-2 expression by ATRA was also parallel to that by ACTD. In conclusion,ATRA can induce apoptosis in macrophage cells, which may be helpful in understanding of immunological functions retinoids.
