Objective To investigate the role of transforming growth factor-β1 （TGF-β1）, Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapr...Objective To investigate the role of transforming growth factor-β1 （TGF-β1）, Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapril and Amlodipine. Methods The renovascular hypertensive rat （RHR） models with ＂two-kidney and one-clip＂ were established, including model group （n = 6）, sham-operated group （n = 6）, Enalapril group （10 mg/kg per day, n = 6）, Amlodipine group （5 mg/kg per day, n = 6） and combination group （Amlodipine 2.5 mg/kg per day ＋ Enalapril 5mg/kg per day, n = 6）. The medication were continuous administrated for six weeks. Carotid artery morphological and structural changes in the media were observed by HE staining, Masson staining and immuno histochemical staining. Media thickness （MT）, MT and lumen diameter ratio （MT/LD）, and the expression levels of media a-smooth muscle actin （α-actin）, proliferating cell nuclear antigen （PCNA）, TGF-β1, phosphorylated Smad2/3 （p-Smad2/3） and Smad7 in carotid arteries were measured. Results The media of carotid arteries in RHR model group was significantly thickened, the volume of smooth muscle cell was increased, and the array was in disorder; MT, MT/LD, the proliferation index of smooth muscle cell and collagen fiber area percentage of carotid arteries in the model group were significantly higher than those in the sham-operated group （P 〈 0.01）. Compared to sham-operated group, the model group had significantly higher expressions of TGF-β1 and p-Smad2/3 （P 〈 0.05） and lower Smad7 expression. Both Enalapril and Amlodipine improved smooth muscle hypertrophy and collagen deposition, reduced RHR carotid MT, MT/LD, proliferation index of smooth muscle cell, collagen fiber area percentage and the expressions of TGF-β1 and p-Smad2/3 （P 〈 0.05）, increased Smad7 expression （P 〈 0.05）. Moreover, the combination treatment of Enalapril and Amlodipine had significantly better effects than single Amlodipine group （P 〈 0.05）, but not single Enalapril group. Conclusions TGF-β1/Smads pathway may participate in the mechanism of carotid artery remodeling in RHR; the role of Amlodipine and Enalapril in inversing carotid artery remodeling may be related to the change of TGF-β1/Smads pathway, the combination treatment of Amlodipine and Enalapril had better effects than single administration of Amlodipine.展开更多
Objective:In traditional herbal medicine(Kampo medicine in Japan),'sho'is diagnosed by the traditional assessments of clinical conditions.Among a variety of the shos,there is an'oketsu'syndrome,which i...Objective:In traditional herbal medicine(Kampo medicine in Japan),'sho'is diagnosed by the traditional assessments of clinical conditions.Among a variety of the shos,there is an'oketsu'syndrome,which is a stagnation and disturbance of microcirculation.The prompt effects of four anti-oketsu formulations in Kampo medicine on cardiovascular functions were compared in oketsu and non-oketsu persons.Methods:The arterial pulse wave from radial artery is formed by the combination with ejection and reflection pulses.An augmentation index(AI),a ration of the ejection and reflection pulses,indicates a degree of arteriosclerosis.For both seventy-six students with oketsu and thirty-seven students with non-oketsu,Kampo formulations overcoming oketsu of Tokishakuyakusan(TS,Dang-Gui-Shao-Yao-San),Kamishoyosan(KS,Jia-Wei-Xiao-Yao-San),Keisibukuryogan(KB,Gui-Zhi-Fu-Ling-Wan)and Tokakujokito(TJ,Tao-He-Cheng-Qi-Tang)were taken once,and then,the cardiovascular functions including blood pressure,heart rate,central arterial blood pressure(CBP)and AI were examined for 60 min.Results:At 40-60 min after an intake,these formulations decreased the AI almost by 6-18%(n=76),by 18.3±3.1%(P<0.01,n=15)with TJ.Simultaneously,the CBP was reduced by 9.0±1.8%(P<0.05,n=23)with KS and by 9.1±2.0%(P<0.05,n=15)with TJ.On the other hands,non-oketsu group had less or no effect by any kinds of the formulations.Conclusion:The anti-oketsu formulations can exert the ameliorative action for oketsu persons via decreasing AI and CBP.展开更多
Objective To evaluate the roles of Na +/H + exchanger-1 (NHE-1)in the proliferation and apoptosis of pulmonary artery smooth muscle cells in rats. Methods Twenty Wistar rats were randomized into control group and ...Objective To evaluate the roles of Na +/H + exchanger-1 (NHE-1)in the proliferation and apoptosis of pulmonary artery smooth muscle cells in rats. Methods Twenty Wistar rats were randomized into control group and 3-week hypoxic group. Intracellular pH (pHi) of the smooth muscle was determined with fluorescence measurement of the pH-sensitive dye BCECF-AM, and the expression of NHE-1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Primary culture of pulmonary artery smooth muscle cells in vitro was performed. In situ cell death detection kit (TUNEL) was used for studying the effect of specific NHE-1 inhibitor-dimethyl amiloride (DMA) on the apoptosis of muscle cells which had intracellular acidification. Results pHi value and NHE-1 mRNA expression of pulmonary artery smooth muscle cells were significantly higher in the hypoxic group than in the control group (P【0.01, P【0.001). DMA elevated the apoptotic ratio remarkably. The effect was enhanced when DMA concentration increased and the time prolonged.Conclusions With the function of adjusting pHi, NHE-1 may play an important role in the proliferation and apoptosis of pulmonary artery smooth muscle cells.展开更多
文摘Objective To investigate the role of transforming growth factor-β1 （TGF-β1）, Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapril and Amlodipine. Methods The renovascular hypertensive rat （RHR） models with ＂two-kidney and one-clip＂ were established, including model group （n = 6）, sham-operated group （n = 6）, Enalapril group （10 mg/kg per day, n = 6）, Amlodipine group （5 mg/kg per day, n = 6） and combination group （Amlodipine 2.5 mg/kg per day ＋ Enalapril 5mg/kg per day, n = 6）. The medication were continuous administrated for six weeks. Carotid artery morphological and structural changes in the media were observed by HE staining, Masson staining and immuno histochemical staining. Media thickness （MT）, MT and lumen diameter ratio （MT/LD）, and the expression levels of media a-smooth muscle actin （α-actin）, proliferating cell nuclear antigen （PCNA）, TGF-β1, phosphorylated Smad2/3 （p-Smad2/3） and Smad7 in carotid arteries were measured. Results The media of carotid arteries in RHR model group was significantly thickened, the volume of smooth muscle cell was increased, and the array was in disorder; MT, MT/LD, the proliferation index of smooth muscle cell and collagen fiber area percentage of carotid arteries in the model group were significantly higher than those in the sham-operated group （P 〈 0.01）. Compared to sham-operated group, the model group had significantly higher expressions of TGF-β1 and p-Smad2/3 （P 〈 0.05） and lower Smad7 expression. Both Enalapril and Amlodipine improved smooth muscle hypertrophy and collagen deposition, reduced RHR carotid MT, MT/LD, proliferation index of smooth muscle cell, collagen fiber area percentage and the expressions of TGF-β1 and p-Smad2/3 （P 〈 0.05）, increased Smad7 expression （P 〈 0.05）. Moreover, the combination treatment of Enalapril and Amlodipine had significantly better effects than single Amlodipine group （P 〈 0.05）, but not single Enalapril group. Conclusions TGF-β1/Smads pathway may participate in the mechanism of carotid artery remodeling in RHR; the role of Amlodipine and Enalapril in inversing carotid artery remodeling may be related to the change of TGF-β1/Smads pathway, the combination treatment of Amlodipine and Enalapril had better effects than single administration of Amlodipine.
文摘Objective:In traditional herbal medicine(Kampo medicine in Japan),'sho'is diagnosed by the traditional assessments of clinical conditions.Among a variety of the shos,there is an'oketsu'syndrome,which is a stagnation and disturbance of microcirculation.The prompt effects of four anti-oketsu formulations in Kampo medicine on cardiovascular functions were compared in oketsu and non-oketsu persons.Methods:The arterial pulse wave from radial artery is formed by the combination with ejection and reflection pulses.An augmentation index(AI),a ration of the ejection and reflection pulses,indicates a degree of arteriosclerosis.For both seventy-six students with oketsu and thirty-seven students with non-oketsu,Kampo formulations overcoming oketsu of Tokishakuyakusan(TS,Dang-Gui-Shao-Yao-San),Kamishoyosan(KS,Jia-Wei-Xiao-Yao-San),Keisibukuryogan(KB,Gui-Zhi-Fu-Ling-Wan)and Tokakujokito(TJ,Tao-He-Cheng-Qi-Tang)were taken once,and then,the cardiovascular functions including blood pressure,heart rate,central arterial blood pressure(CBP)and AI were examined for 60 min.Results:At 40-60 min after an intake,these formulations decreased the AI almost by 6-18%(n=76),by 18.3±3.1%(P<0.01,n=15)with TJ.Simultaneously,the CBP was reduced by 9.0±1.8%(P<0.05,n=23)with KS and by 9.1±2.0%(P<0.05,n=15)with TJ.On the other hands,non-oketsu group had less or no effect by any kinds of the formulations.Conclusion:The anti-oketsu formulations can exert the ameliorative action for oketsu persons via decreasing AI and CBP.
文摘Objective To evaluate the roles of Na +/H + exchanger-1 (NHE-1)in the proliferation and apoptosis of pulmonary artery smooth muscle cells in rats. Methods Twenty Wistar rats were randomized into control group and 3-week hypoxic group. Intracellular pH (pHi) of the smooth muscle was determined with fluorescence measurement of the pH-sensitive dye BCECF-AM, and the expression of NHE-1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Primary culture of pulmonary artery smooth muscle cells in vitro was performed. In situ cell death detection kit (TUNEL) was used for studying the effect of specific NHE-1 inhibitor-dimethyl amiloride (DMA) on the apoptosis of muscle cells which had intracellular acidification. Results pHi value and NHE-1 mRNA expression of pulmonary artery smooth muscle cells were significantly higher in the hypoxic group than in the control group (P【0.01, P【0.001). DMA elevated the apoptotic ratio remarkably. The effect was enhanced when DMA concentration increased and the time prolonged.Conclusions With the function of adjusting pHi, NHE-1 may play an important role in the proliferation and apoptosis of pulmonary artery smooth muscle cells.
