In order to study the dynamic and electrical coupling response characteristics of Metal Oxide Semiconductor Controlled Thyristor(MCT)high-voltage switch under the synergic action of mechanical load and high voltage,th...In order to study the dynamic and electrical coupling response characteristics of Metal Oxide Semiconductor Controlled Thyristor(MCT)high-voltage switch under the synergic action of mechanical load and high voltage,the separated Hopkinson pressure bar(SHPB)test system was used to simulate different impact load environments,and combined with the multi-layer high-voltage ceramic capacitor charging and discharging system,the instantaneous electrical signals of MCT high-voltage switch were collected.Combined with numerical simulation and theoretical analysis,the failure mode and stress wave propagation characteristics of MCT high voltage switch were determined.The mechanical and electrical coupling response characteristics and failure mechanism of MCT high voltage switch under dynamic load were revealed from macroscopic and microscopic levels.The results show that the damage modes of MCT high-voltage switches can be divided into non-functional damage,recoverable functional damage,non-recoverable damage and structural damage.Due to the gap between the metal gate and the oxide layer,the insulating oxide layer was charged.After placing for a period of time,the elastic deformation of the metal gate partially recovered and the accumulated charge disappeared,which induced the recoverable functional damage failure of the device.In addition,obvious cracks appeared on both sides of the monocrystalline silicon inside the MCT high-voltage switch,leading to unrecoverable damage of the device.展开更多
Pulmonary arterial hypertension （PAH） is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature. Quercetin is a natural fiavonoid and has a variety of pharmacologica...Pulmonary arterial hypertension （PAH） is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature. Quercetin is a natural fiavonoid and has a variety of pharmacological effects including improvement of endothelial cell function. However, its pharmacological effects on pulmonary hypertension have been rarely reported. We sought to observe the protective effect of quercetin in rats with monocrotaline induced PAH. We divided 30 male Sprague-Dawley rats randomly into three groups with ten rats in each group： the monocrotaline group, the quercetin group and the control group. We found that, compared with the controls, the mean pulmonary artery pressure （mPAP） and the right ventricular hypertrophy index in the monocrotaline group were significantly higher （P 〈 0.01）. Quercetin caused a significant reduction both in the mPAP and fight ventricular hypertrophy index compared with the monocrotaline group （P 〈 0.01） while no difference was found between the quercefin group and the control group （P 〉 0.05）. Monocrotaline induced a marked increase in the wall thickness （WT） in small and mid-sized pulmonary arteries compared with the controls （P 〈 0.01）. Monocrotaline also induced a marked increase in the wall area （WA） in small [（56.38 ±6.65）% in monocrotaline vs. （19.80±4.63）% in control] and mid-sized [（43.71± 5.38）% in monocrotaline vs. （14.24± 3.66）% in control] pulmonary arteries （P 〈 0.01）. Quercefin treatment markedly reduced monocrotaline induced increase in both WT and WA （P 〈 0.01）, which, however, still remained significantly elevated compared with those of the controls （P 〈 0.01）. Furthermore, compared with controls, proliferating cell nuclear antigen （PCNA） expression in the pulmonary artery tissues was markedly increased by monocrotaline [（45.59± 1.27） in monocrotaline vs. （9.64± 0.69） in controls], which was significantly attenuated by quercetin. Our animal experiment indicated that quercetin could have protective effects on monocrotaline-induced PAH.展开更多
BACKGROUND:Hepatic veno-occlusive disease(HVOD)is a severe complication of chemotherapy before hematopoietic stem cell transplantation and dietary ingestion of pyrrolizidine alkaloids.Many experimental models were est...BACKGROUND:Hepatic veno-occlusive disease(HVOD)is a severe complication of chemotherapy before hematopoietic stem cell transplantation and dietary ingestion of pyrrolizidine alkaloids.Many experimental models were established to study its mechanisms or therapy,but few are ideal.This work aimed at evaluating a rat model of HVOD induced by monocrotaline to help advance research into this disease. METHODS:Thirty-two male rats were randomly classified into 5 groups,and PBS or monocrotaline was administered (100 mg/kg or 160 mg/kg).They were sacrificed on day 7(groups A,B and D)or day 10(groups C and E).Blood samples were collected to determine liver enzyme concentrations.The weight of the liver and body and the amount of ascites were measured.Histopathological changes of liver tissue on light microscopy were assessed by a modified Deleve scoring system.The positivity of proliferating cell nuclear antigen(PCNA)was estimated. RESULTS:The rats that were treated with 160 mg/kg monocrotaline presented with severe clinical symptoms (including two deaths)and the histopathological picture of HVOD.On the other hand,the rats that were fed with 100 mg/kg monocrotaline had milder and reversible manifestations.Comparison of the rats sacrificed on day 10 with those sacrificed on day 7 showed that the positivity of PCNA increased,especially that of hepatocytes.CONCLUSIONS:Monocrotaline induces acute,dose- dependent HVOD in rats.The model is potentially reversible with a low dose,but reliable and irreversible with a higher dose.The modified scoring system seems to be more accurate than the traditional one in reflecting the histopathology of HVOD.The enhancement of PCNA positivity may be associated with hepatic tissue undergoing recovery.展开更多
To observe changes in activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in rats with monocrotaline-induced pulmonary hypertension. Methods: Adult ma1e Sprague-Dawley rats were given a single ...To observe changes in activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in rats with monocrotaline-induced pulmonary hypertension. Methods: Adult ma1e Sprague-Dawley rats were given a single subcutaneous injection of monocrotaline (MCT, 60 mg/kg) for modeling PH. Activities of SOD and contents of MDA in plasma and pulmonary homogenate were measured by colorimetric analysis. The thickness of the media of pulmonary arterioles (external diameter <100μm) was measured using colour image analysis system. Results: Four weeks after injection of MCT, activities of SOD in venous plasma and pulmonary homogenate for MCT group were 106±45 NU/ml (P<0.05) and 317±59 NU/ml (P<0.01) respectively, whileactivities of SOD for control group were 159±28 NU/ml (P<0.05) and 505±47 NU/ml (P<0.01) respectively.COntents of MDA in venous plasma and pulmonary homogenate for MCT group were 15±5 and 59±14 μmol/L,while contents of MDA for control group were 5. 3±2. 8 and 32±19 ±mol/L. The thickness of the media of pulmonary arterioles increased significantly. Conclusion: The primary cause of PH is the injury of pulmonary vascular endothelial cells by MCT, which decreases the O2 removing ability of the lungs but increases lipid peroxidation,thus inducing PH.展开更多
Precision-cut liver slice has been successfully used to study the mechanism of drug-induced hepatotoxicity, the prediction of liver toxicity, the discovery of early hepatic toxicity biomarker and the metabolism of dru...Precision-cut liver slice has been successfully used to study the mechanism of drug-induced hepatotoxicity, the prediction of liver toxicity, the discovery of early hepatic toxicity biomarker and the metabolism of drug in liver. We detected the expression of CYP3A4, CYP2B1 + CYP2B2 and CYP2E1 in precision-cut liver slice after co-cultured with monocrotaline or Tussilago farfara alkaloids to investigate the hepatotoxicity mechanism of those drugs. After co-culturing with monocrotaline or Tussilago farfara alkaloids for 6 hours, the expression of CYP3A4 in the microsome of precision-cut liver slices was detected by Western blot, and the expressions of CYP2B1 + CYP2B2 and CYP2E1 were detected by immunofluorescence. The results showed that monocrotaline induced the expression of CYP3A4 and CYP2B1 + CYP2B2, and Tussilago farfara alkaloids obviously up-regulated the expression of CYP2E1 and CYP3A4. Thus, we conclude that the up-regulation of CYP3A4, CYP2B1 + CYP2B2 and CYP2E1 may be one of the toxic mechanisms of liver injury of those drugs.展开更多
OBJECTIVE Salvianolic acid A(SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge) and exhibits many pharmaco.logical activities.Previous studies ha...OBJECTIVE Salvianolic acid A(SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge) and exhibits many pharmaco.logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats.However,whether SAA improves vascular remodeling induced by pulmonary arterial hypertension(PAH) remains unknown.In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline(MCT 60 mg·kg^(-1)).The rats were orally treated with either SAA(0.3,1,3 mg·kg^(-1)·d^(-1)) or a positive con.trol Bosentan(30 mg·kg^(-1)·d^(-1)) for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab.normalities and the subsequent increases of right ventricular systolic pressure(RVSP).Furthermore,the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in.jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge.netic protein type Ⅱ receptor(BMPR Ⅱ) and phosphorylated Smad1/5 in the lungs.CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa.tients at high risk of PAH.展开更多
基金Youth Talent Project of Basic Scientific Research Project of Liaoning Province Education Department(Grant No.LJKZ0270)Youth Project of Basic Scientific Research Project of Liaoning Province Education Department(Grant No.LJKQZ2021055).
文摘In order to study the dynamic and electrical coupling response characteristics of Metal Oxide Semiconductor Controlled Thyristor(MCT)high-voltage switch under the synergic action of mechanical load and high voltage,the separated Hopkinson pressure bar(SHPB)test system was used to simulate different impact load environments,and combined with the multi-layer high-voltage ceramic capacitor charging and discharging system,the instantaneous electrical signals of MCT high-voltage switch were collected.Combined with numerical simulation and theoretical analysis,the failure mode and stress wave propagation characteristics of MCT high voltage switch were determined.The mechanical and electrical coupling response characteristics and failure mechanism of MCT high voltage switch under dynamic load were revealed from macroscopic and microscopic levels.The results show that the damage modes of MCT high-voltage switches can be divided into non-functional damage,recoverable functional damage,non-recoverable damage and structural damage.Due to the gap between the metal gate and the oxide layer,the insulating oxide layer was charged.After placing for a period of time,the elastic deformation of the metal gate partially recovered and the accumulated charge disappeared,which induced the recoverable functional damage failure of the device.In addition,obvious cracks appeared on both sides of the monocrystalline silicon inside the MCT high-voltage switch,leading to unrecoverable damage of the device.
文摘Pulmonary arterial hypertension （PAH） is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature. Quercetin is a natural fiavonoid and has a variety of pharmacological effects including improvement of endothelial cell function. However, its pharmacological effects on pulmonary hypertension have been rarely reported. We sought to observe the protective effect of quercetin in rats with monocrotaline induced PAH. We divided 30 male Sprague-Dawley rats randomly into three groups with ten rats in each group： the monocrotaline group, the quercetin group and the control group. We found that, compared with the controls, the mean pulmonary artery pressure （mPAP） and the right ventricular hypertrophy index in the monocrotaline group were significantly higher （P 〈 0.01）. Quercetin caused a significant reduction both in the mPAP and fight ventricular hypertrophy index compared with the monocrotaline group （P 〈 0.01） while no difference was found between the quercefin group and the control group （P 〉 0.05）. Monocrotaline induced a marked increase in the wall thickness （WT） in small and mid-sized pulmonary arteries compared with the controls （P 〈 0.01）. Monocrotaline also induced a marked increase in the wall area （WA） in small [（56.38 ±6.65）% in monocrotaline vs. （19.80±4.63）% in control] and mid-sized [（43.71± 5.38）% in monocrotaline vs. （14.24± 3.66）% in control] pulmonary arteries （P 〈 0.01）. Quercefin treatment markedly reduced monocrotaline induced increase in both WT and WA （P 〈 0.01）, which, however, still remained significantly elevated compared with those of the controls （P 〈 0.01）. Furthermore, compared with controls, proliferating cell nuclear antigen （PCNA） expression in the pulmonary artery tissues was markedly increased by monocrotaline [（45.59± 1.27） in monocrotaline vs. （9.64± 0.69） in controls], which was significantly attenuated by quercetin. Our animal experiment indicated that quercetin could have protective effects on monocrotaline-induced PAH.
文摘BACKGROUND:Hepatic veno-occlusive disease(HVOD)is a severe complication of chemotherapy before hematopoietic stem cell transplantation and dietary ingestion of pyrrolizidine alkaloids.Many experimental models were established to study its mechanisms or therapy,but few are ideal.This work aimed at evaluating a rat model of HVOD induced by monocrotaline to help advance research into this disease. METHODS:Thirty-two male rats were randomly classified into 5 groups,and PBS or monocrotaline was administered (100 mg/kg or 160 mg/kg).They were sacrificed on day 7(groups A,B and D)or day 10(groups C and E).Blood samples were collected to determine liver enzyme concentrations.The weight of the liver and body and the amount of ascites were measured.Histopathological changes of liver tissue on light microscopy were assessed by a modified Deleve scoring system.The positivity of proliferating cell nuclear antigen(PCNA)was estimated. RESULTS:The rats that were treated with 160 mg/kg monocrotaline presented with severe clinical symptoms (including two deaths)and the histopathological picture of HVOD.On the other hand,the rats that were fed with 100 mg/kg monocrotaline had milder and reversible manifestations.Comparison of the rats sacrificed on day 10 with those sacrificed on day 7 showed that the positivity of PCNA increased,especially that of hepatocytes.CONCLUSIONS:Monocrotaline induces acute,dose- dependent HVOD in rats.The model is potentially reversible with a low dose,but reliable and irreversible with a higher dose.The modified scoring system seems to be more accurate than the traditional one in reflecting the histopathology of HVOD.The enhancement of PCNA positivity may be associated with hepatic tissue undergoing recovery.
文摘To observe changes in activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in rats with monocrotaline-induced pulmonary hypertension. Methods: Adult ma1e Sprague-Dawley rats were given a single subcutaneous injection of monocrotaline (MCT, 60 mg/kg) for modeling PH. Activities of SOD and contents of MDA in plasma and pulmonary homogenate were measured by colorimetric analysis. The thickness of the media of pulmonary arterioles (external diameter <100μm) was measured using colour image analysis system. Results: Four weeks after injection of MCT, activities of SOD in venous plasma and pulmonary homogenate for MCT group were 106±45 NU/ml (P<0.05) and 317±59 NU/ml (P<0.01) respectively, whileactivities of SOD for control group were 159±28 NU/ml (P<0.05) and 505±47 NU/ml (P<0.01) respectively.COntents of MDA in venous plasma and pulmonary homogenate for MCT group were 15±5 and 59±14 μmol/L,while contents of MDA for control group were 5. 3±2. 8 and 32±19 ±mol/L. The thickness of the media of pulmonary arterioles increased significantly. Conclusion: The primary cause of PH is the injury of pulmonary vascular endothelial cells by MCT, which decreases the O2 removing ability of the lungs but increases lipid peroxidation,thus inducing PH.
文摘Precision-cut liver slice has been successfully used to study the mechanism of drug-induced hepatotoxicity, the prediction of liver toxicity, the discovery of early hepatic toxicity biomarker and the metabolism of drug in liver. We detected the expression of CYP3A4, CYP2B1 + CYP2B2 and CYP2E1 in precision-cut liver slice after co-cultured with monocrotaline or Tussilago farfara alkaloids to investigate the hepatotoxicity mechanism of those drugs. After co-culturing with monocrotaline or Tussilago farfara alkaloids for 6 hours, the expression of CYP3A4 in the microsome of precision-cut liver slices was detected by Western blot, and the expressions of CYP2B1 + CYP2B2 and CYP2E1 were detected by immunofluorescence. The results showed that monocrotaline induced the expression of CYP3A4 and CYP2B1 + CYP2B2, and Tussilago farfara alkaloids obviously up-regulated the expression of CYP2E1 and CYP3A4. Thus, we conclude that the up-regulation of CYP3A4, CYP2B1 + CYP2B2 and CYP2E1 may be one of the toxic mechanisms of liver injury of those drugs.
基金supported by National Natural Science Foundation of China(8177393581573645+1 种基金81603101) CAMS Innovation Fund for Medical Sciences(2017-I2M-1-010)
文摘OBJECTIVE Salvianolic acid A(SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge) and exhibits many pharmaco.logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats.However,whether SAA improves vascular remodeling induced by pulmonary arterial hypertension(PAH) remains unknown.In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline(MCT 60 mg·kg^(-1)).The rats were orally treated with either SAA(0.3,1,3 mg·kg^(-1)·d^(-1)) or a positive con.trol Bosentan(30 mg·kg^(-1)·d^(-1)) for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab.normalities and the subsequent increases of right ventricular systolic pressure(RVSP).Furthermore,the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in.jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge.netic protein type Ⅱ receptor(BMPR Ⅱ) and phosphorylated Smad1/5 in the lungs.CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa.tients at high risk of PAH.
