Summary: To explore the pharmacological effect of 3,4-dihydroxyacetophenone (DHAP) on the apoptosis of RAW264.7 macrophage cells and the mechanism, RAW264.7 macrophage cells were treated with 100 or 500 mg/L lipopoly...Summary: To explore the pharmacological effect of 3,4-dihydroxyacetophenone (DHAP) on the apoptosis of RAW264.7 macrophage cells and the mechanism, RAW264.7 macrophage cells were treated with 100 or 500 mg/L lipopolysaccharide (LPS), with or without 10 -5 mol/L DHAP for 24 h. Trypan blue dye exclusion assay was used to assess cell viability. Cell apoptosis was morphological studied and flow cytometric assay was used. Tumor necrosis factor-α (TNF-α) level was measured by ELISA methods. IκB protein was determined by Western blotting. Our results showed that in 100 mg/L LPS-stimulated macrophages, DHAP enhanced the cell apoptosis while in 500 mg/L LPS-stimulated macrophages, DHAP significantly inhibited the cell apoptosis. In both groups, DHAP increased the level of IκB but decreased the level of TNF-α. It is concluded that DHAP has dual effect on the apoptosis of RAW 264.7 cells treated with different concentrations of LPS. This effect may be due to the inhibition of activation of NF-κB and autocrine production of TNFα. Our study suggests that DHAP may have anti-inflammatory effect on LPS-activated macrophages.展开更多
The effects of 3,4-DHAP on hypoxic pulmonary and systemic vascular responses were studied in anaesthetized dogs. The percentage change in pulmonary vascular resistance(△PVR%)and that in systemic vascular resistance(...The effects of 3,4-DHAP on hypoxic pulmonary and systemic vascular responses were studied in anaesthetized dogs. The percentage change in pulmonary vascular resistance(△PVR%)and that in systemic vascular resistance(△SVR%)induced by 5 min hypoxia decreased significantly.3,4-DHAP in doses of 1 mg/kg,3mg/kg,and 10 mg/kg i.v caused a decrease in b PVR% from the control value of 47.27±22.27% to 24.62±21.76%,18.15±18.73%,and 24.10±19.76% respectively, and a decrease in △SVR% from the control value of 12.91±7.39% to -0.34±12.7%,-2.11±12.76%,and -2.37±15.52% respectively.The results showed that 3,4-DHAP could decrease the hypoxic responses of pulmonary and systemic blood vessels.But it did not change △PVR% or △SVR% in dose of 30mg/kg,neither did it influence the heart rate,cardiac output or cerebral blood flow during hypoxia in all the doses used.展开更多
The effects of 3, 4-DHAP on hypoxic vasoconstriction response in pulmonary (PA) and basilar arterial(BA) rings of rabbits and their mechanism were compared in vitro.3,4-DHAP in different concentration (2.64×10-4,...The effects of 3, 4-DHAP on hypoxic vasoconstriction response in pulmonary (PA) and basilar arterial(BA) rings of rabbits and their mechanism were compared in vitro.3,4-DHAP in different concentration (2.64×10-4,7.92×10-4,2.376×10-3mol/L) decreased the basal tone of PA rings by 32. 39±9.4 mg, 68. 96±26. 54 mg and 145. 60±58.07 mg respectively,while the tension of the BA rings was decreased by 13. 80±5. 08 mg,17.18±3.36 mg and 25. 00±4.02 mg respectively.In PA rings it also decreased the percentage increase in tension induced by hypoxia(TIH%)from the control value 48. 82±5.75% to 10.02±3. 62%,2.14±0.96%, and 0.00% respectively, while in BA rings from 27.27±5.78% to 11. 23±2.71%,7.49±1. 62%, and 1.45±1.13% respectively. The effects of 3,4-DHAP on TIH% were partially blocked by indomethacin 10 M and L-NWE 10 M.The results showed that 3, 4-DHAP can decrease the hypoxic pulmonary and basilar vasoconstriction in vitro. which can be partially inhibited by cyclooxygenase inhibitor and NO/EDRF inhibitor.展开更多
In order to study the effect of dihydroxyacetophenone ( DHAP) on pulmonary hemodynamicsand its relationship to plasma atrial natriuretic peptide (ANP) as well as adenosine cyclophosphates in chron-ic obstractive pulmo...In order to study the effect of dihydroxyacetophenone ( DHAP) on pulmonary hemodynamicsand its relationship to plasma atrial natriuretic peptide (ANP) as well as adenosine cyclophosphates in chron-ic obstractive pulmonary disease (COPD) , right heart catheterization was used to examine some parametersof hemodynamics in 11 COPD patients before and after the application of DHAP, and at the same time ra-dioimmunoassay was used to measure the plasma ANP and cyclo-adenosine monophosphate/cyclic guanosinemonophosphate (cAMP/cGMP) . The results showed that DHAP 640 mg given intravenously could decreasemean pulmonary arterial pressure, pulmonary vascular resistance and systemic vascular resistance ( P <0 . 05) , but increase cardiac output from 4. 10 ±1 . 08 L/min to 5.13 ± 1 . 19 L/min ( P>0. 05) and without af-fecting systemic arterial blood pressure ( P >0. 05) as well as blood gas analysis; it could also reduce theplasma ANP and cGMP Ievel from 0. 73 ± 0. 42 pg/ml to 0. 41 ± 0. 33 pg/ml ( P<0. 01 ) and trom 9 . 82 ± 5. 75pm/ml to 8. 01 ± 4. 80 pm/ml( P< 0. 05) respectively, but did not affect the plasma cAMP level ( P>0. 05) .It is suggested that DHAP may relax pulmonary vessels by adjusting the ratio of cAMP to cGMP, and the low-ering of plasma ANP level might be a secondary reaction. So DHAP was considered a quick-acting, safe andpotential drug in treating pulmonary arterial hypertension by COPD.展开更多
基金This project was supported by grants of the National Natu ral Scientific Foundation of China (No. 30070929) and (No.30100226).
文摘Summary: To explore the pharmacological effect of 3,4-dihydroxyacetophenone (DHAP) on the apoptosis of RAW264.7 macrophage cells and the mechanism, RAW264.7 macrophage cells were treated with 100 or 500 mg/L lipopolysaccharide (LPS), with or without 10 -5 mol/L DHAP for 24 h. Trypan blue dye exclusion assay was used to assess cell viability. Cell apoptosis was morphological studied and flow cytometric assay was used. Tumor necrosis factor-α (TNF-α) level was measured by ELISA methods. IκB protein was determined by Western blotting. Our results showed that in 100 mg/L LPS-stimulated macrophages, DHAP enhanced the cell apoptosis while in 500 mg/L LPS-stimulated macrophages, DHAP significantly inhibited the cell apoptosis. In both groups, DHAP increased the level of IκB but decreased the level of TNF-α. It is concluded that DHAP has dual effect on the apoptosis of RAW 264.7 cells treated with different concentrations of LPS. This effect may be due to the inhibition of activation of NF-κB and autocrine production of TNFα. Our study suggests that DHAP may have anti-inflammatory effect on LPS-activated macrophages.
文摘The effects of 3,4-DHAP on hypoxic pulmonary and systemic vascular responses were studied in anaesthetized dogs. The percentage change in pulmonary vascular resistance(△PVR%)and that in systemic vascular resistance(△SVR%)induced by 5 min hypoxia decreased significantly.3,4-DHAP in doses of 1 mg/kg,3mg/kg,and 10 mg/kg i.v caused a decrease in b PVR% from the control value of 47.27±22.27% to 24.62±21.76%,18.15±18.73%,and 24.10±19.76% respectively, and a decrease in △SVR% from the control value of 12.91±7.39% to -0.34±12.7%,-2.11±12.76%,and -2.37±15.52% respectively.The results showed that 3,4-DHAP could decrease the hypoxic responses of pulmonary and systemic blood vessels.But it did not change △PVR% or △SVR% in dose of 30mg/kg,neither did it influence the heart rate,cardiac output or cerebral blood flow during hypoxia in all the doses used.
文摘The effects of 3, 4-DHAP on hypoxic vasoconstriction response in pulmonary (PA) and basilar arterial(BA) rings of rabbits and their mechanism were compared in vitro.3,4-DHAP in different concentration (2.64×10-4,7.92×10-4,2.376×10-3mol/L) decreased the basal tone of PA rings by 32. 39±9.4 mg, 68. 96±26. 54 mg and 145. 60±58.07 mg respectively,while the tension of the BA rings was decreased by 13. 80±5. 08 mg,17.18±3.36 mg and 25. 00±4.02 mg respectively.In PA rings it also decreased the percentage increase in tension induced by hypoxia(TIH%)from the control value 48. 82±5.75% to 10.02±3. 62%,2.14±0.96%, and 0.00% respectively, while in BA rings from 27.27±5.78% to 11. 23±2.71%,7.49±1. 62%, and 1.45±1.13% respectively. The effects of 3,4-DHAP on TIH% were partially blocked by indomethacin 10 M and L-NWE 10 M.The results showed that 3, 4-DHAP can decrease the hypoxic pulmonary and basilar vasoconstriction in vitro. which can be partially inhibited by cyclooxygenase inhibitor and NO/EDRF inhibitor.
文摘In order to study the effect of dihydroxyacetophenone ( DHAP) on pulmonary hemodynamicsand its relationship to plasma atrial natriuretic peptide (ANP) as well as adenosine cyclophosphates in chron-ic obstractive pulmonary disease (COPD) , right heart catheterization was used to examine some parametersof hemodynamics in 11 COPD patients before and after the application of DHAP, and at the same time ra-dioimmunoassay was used to measure the plasma ANP and cyclo-adenosine monophosphate/cyclic guanosinemonophosphate (cAMP/cGMP) . The results showed that DHAP 640 mg given intravenously could decreasemean pulmonary arterial pressure, pulmonary vascular resistance and systemic vascular resistance ( P <0 . 05) , but increase cardiac output from 4. 10 ±1 . 08 L/min to 5.13 ± 1 . 19 L/min ( P>0. 05) and without af-fecting systemic arterial blood pressure ( P >0. 05) as well as blood gas analysis; it could also reduce theplasma ANP and cGMP Ievel from 0. 73 ± 0. 42 pg/ml to 0. 41 ± 0. 33 pg/ml ( P<0. 01 ) and trom 9 . 82 ± 5. 75pm/ml to 8. 01 ± 4. 80 pm/ml( P< 0. 05) respectively, but did not affect the plasma cAMP level ( P>0. 05) .It is suggested that DHAP may relax pulmonary vessels by adjusting the ratio of cAMP to cGMP, and the low-ering of plasma ANP level might be a secondary reaction. So DHAP was considered a quick-acting, safe andpotential drug in treating pulmonary arterial hypertension by COPD.
