BACKGROUND: Melatonin exerts complex physiological and pharmacological effects on multiple systems and organs. We hypothesized that melatonin might abate ischemia/ reperfusion (I/R) injury in the liver by inhibiting e...BACKGROUND: Melatonin exerts complex physiological and pharmacological effects on multiple systems and organs. We hypothesized that melatonin might abate ischemia/ reperfusion (I/R) injury in the liver by inhibiting excessive oxidative stress and keeping nitric oxide (NO) from being scavenged by free radicals. The aim of the present study was to investigate whether melatonin protects the liver from I/R injury and, if so, by what underlying mechanism. METHODS: Under anesthesia, Wistar rats were intraperi- toneally injected with 20 mg/kg melatonin (dissolved in physiological saline containing 4% ethanol, Mel group), 4% alcohol (Alc group), or physiological saline (NS group). The artery, portal vein and bile duct of the left lobe of the liver were clamped for 60 minutes and then released. At different time points after I/R, the rats were sacrificed and blood samples were collected to measure the levels of serum alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and NO. Hepatic tissue samples were collected for measuring endothelin expression by immunohistochemical staining and for routine morphological and histological examination. RESULTS: The levels of both ALT and LDH in the Mel group were significantly reduced for up to 24 hours after I/R compared with the Alc and NS groups (P<0.05). The levels of NO in the Mel group were significantly elevated for up to 12 hours after I/R relative to the NS group (P<0.05). The NO levels were also elevated at 0.5 and 6 hours after I/R in the Alc group (P<0.05). The immunohistochemical staining of hepatic tissue showedthat endothelin-positive cells were significantly fewer in the Mel group than in the Alc and NS groups at 6 hours after I/R (P<0.01). The necrosis of hepatocytes and the destruction of hepatic cords in the Alc and NS groups were greatly improved in Mel-treated rats, which is in concert with our functional data. CONCLUSIONS: Pretreatment with melatonin increased NO bioavailability and decreased endothelin expression, and consequently played a protective role in preserving both liver function and structure during ischemia and reperfusion injury.展开更多
Objective: To explore the changes of plasma endothelin(ET) and nitric oxide (NO) levels in patients with a-cute pancreatitis.Methods: The level of plasma ET was measured by ra-dioactive-immunoassay, and NO by spectrop...Objective: To explore the changes of plasma endothelin(ET) and nitric oxide (NO) levels in patients with a-cute pancreatitis.Methods: The level of plasma ET was measured by ra-dioactive-immunoassay, and NO by spectrophotometry.Results: The levels of ET, NO and the ET/NO ratioin patients with severe acute pancreatitis(SAP) within24 hours in hospital were all significantly higher thanthose in other groups of patients [(176±8)pg/ml,(97±11) μmol/L, and 1.83±0.12, P<0.01]. Com-pared to healthy controls(N), the levels of ET and NOin patients without pancreatitis acute abdomen (NAP)and patients with mild acute pancreatitis (MAP) in-creased significantly (P<0.01). After appropriate treat-ment, the levels of ET and NO in the MAP groupwere lower (P<0.01). Compared with those beforetreatment, the levels of ET and NO in the SAP groupon the 3rd and 7th day in hospital dropped signifi-cantly(P<0.01).The ET/NO ratio on the 7th daywas also lower than that on admission (P<0.01).Conclusions: The malfunction of endothelial cells andthe increased ET/NO ratio may be related to the mecha-nism of pancreatic microcirculatory disturbance in pa-tients with SAP; early dynamic determination of theseparameters may help predict the prognosis of SAP.展开更多
AIM： To investigate the perioperative changes of nitric oxide （NO） and endothelin （ET）, thromboxane A2 （TXA2） and prostaglandin （PGI2） during liver transplantation in end-stage liver disease patients. METHODS...AIM： To investigate the perioperative changes of nitric oxide （NO） and endothelin （ET）, thromboxane A2 （TXA2） and prostaglandin （PGI2） during liver transplantation in end-stage liver disease patients. METHODS： Twenty-seven patients with end-stage cirrhosis undergoing liver transplantation were enrolled in this prospective study. Blood samples were obtained from superior vena at five different surgical stages. Plasma concentrations of nitrate and nitrite were determined to reflect plasma NO levels. Plasma levels of ET-1, 6-keto-PGF1 alpha and thromboxane B2 （TXB2）, the latter two being stable metabolites of PGI2 and TXA2 respectively, were measured.RESULTS： The NO level decreased significantly after vascular cross-clamping and increased significantly at 30 rain after reperfusion. While the ET levels at 30 rain after clamping and after reperfusion were significantly elevated. The ratio of NO/ET decreased significantly at 30 rain after vascular cross-clamping and at the end of surgery. The PGI2 level and the TXA2 during liver transplantation were significantly higher than the baseline level, but the ratio of TXA2/PGI2 decreased significantly at 30 rain after clamping. CONCLUSION： NO/ET and TXA2/PGI2 change during liver transplantation. Although the precise mechanism remains unknown, they may play a role in the pathobiology of a variety of liver transplant-relevant processes.展开更多
Objective To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension(PAH) in patients of chronic obstructive pulmonary disease(COPD) associated with chronic cor pulmonale(C...Objective To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension(PAH) in patients of chronic obstructive pulmonary disease(COPD) associated with chronic cor pulmonale(CCP) during exacerbation.Methods Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group.The control group received standard treatment with antibiotics,antiasthmatic and expectorant medications,and oxygenation;and the ligustrazine treatment group received ligustrazine treatment(80 mg/d;i.v.;for 2 weeks) in addition to the standard treatment.Before and at the end of 2 week treatment,the clinic responses of the two regimens were evaluated,plasma levels of endothelin-1(ET-1) and nitric oxide(NO) were determined;arterial oxygen partial pressure(PaO_2),mean pulmonary arterial pressure(mPAP),outflow tract of right ventricle(RVOT),and internal diameter of right ventricle(RV) were measured.Results Good clinic benefits were achieved in both the standard and ligustrazine regimens,plasma level of ET-1,values of mPAP,RV and RVOT decreased significantly,plasma level of NO and PaO_2 values decreased(all P<0.01 vs pretreatment to all parameters).Compared with the control group,ligustrazine greatly enhanced the clinic efficacy from 77.1%to 97.1%(P<0.05),and also resulted in more significant changes of all these parameters(P<0.01 vs control group for all parameters).For both groups,the levels of plasma ET-1 were positively correlated with values of mPAP,RVOT,and RV(r = 0.710,0.853,and 0.766,respectively,all P = 0.000),and negatively correlated with plasma NO and PaO_2(r =- 0.823,and- 0.752,respectively,all P = 0.000).Conclusion Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area.The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells,thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.展开更多
[ Objective] To observe effect of Chanfukang on vascular endothelial cells of postpartum cows with Oi deficiency and Blood stasis, and to explore the treatment mechanism of Chanfukang. [Method] A total of 58 cows were...[ Objective] To observe effect of Chanfukang on vascular endothelial cells of postpartum cows with Oi deficiency and Blood stasis, and to explore the treatment mechanism of Chanfukang. [Method] A total of 58 cows were assigned to four groups. The cows in group 1 and group 2 suffered from Qi deficiency and Blood stasis. The cows in group 1 were gavaged with Chanfukang （0.5 g/kg-BW, 5 d） at 12 h post partum, but the cows in group 2 were not treated. The cows in group 3 were healthy and gavaged with Chanfukang （0.4 g/kg.BW, 5 d） at 12 h post partum. Cows in group 4 were healthy control cows. The plasma endothelin （ET） concentration and serum nitric oxide （NO） concentration were determined before and after parturition, respectively. [ Result ] The plasma ET concentration and serum NO concentration were significantly higher in the cows with Qi deficiency and Blood stasis than in the healthy control cows （P 〈 0.05）. The NO concentration decreased on Day 10 post partum in the cows with Qi deficiency and Blood stasis, but it was still higher than that in the healthy control cows. After taking Chanfukang for 7 d, the ET concentration and NO concentration decreased, and no significant difference was found between the cows with Qi deficiency and Blood stasis treated with Chanfukang and the healthy control cows. [ Conclusion] Chanfukang may relieve Qi deficiency and Blood stasis of postpartum cows through decreasing plasma ET concentration and serum NO concentration.展开更多
Objective: To observe the effect of purified Xuefu Capsule （PXC） on endothelin （ET） and nitric oxide synthetase （NOS） gene expression and proliferation of vascular smooth muscle cell （VSMC） in atherosclerotic ...Objective: To observe the effect of purified Xuefu Capsule （PXC） on endothelin （ET） and nitric oxide synthetase （NOS） gene expression and proliferation of vascular smooth muscle cell （VSMC） in atherosclerotic rabbits. Methods: Molecular biological techniques of dot blot and in situ hybridization were adopted. Results: The expression of ET mRNA in atherosclerosis （AS）, plaques of the model group was higher,with the positive signals distributed mainly in arterial intimal AS plaques; while at the same time the expression in the PXC treated group was lower, with only few scattering signals found in arterial intimal AS plaques.NOS mRNA expression was less in the vascular wall of the AS model group, PXC could enhance NOS mRNA expression, positive signals could be found from intima to media. Conclusion: The effect of PXC on preventing and treating AS might be related to regulating the expression of ET mRNA and NOS mRNA in the vascular wall.展开更多
基金This study was supported by a grant from Nature Science Foundation of Liaoning Province of China (No. 20042064).
文摘BACKGROUND: Melatonin exerts complex physiological and pharmacological effects on multiple systems and organs. We hypothesized that melatonin might abate ischemia/ reperfusion (I/R) injury in the liver by inhibiting excessive oxidative stress and keeping nitric oxide (NO) from being scavenged by free radicals. The aim of the present study was to investigate whether melatonin protects the liver from I/R injury and, if so, by what underlying mechanism. METHODS: Under anesthesia, Wistar rats were intraperi- toneally injected with 20 mg/kg melatonin (dissolved in physiological saline containing 4% ethanol, Mel group), 4% alcohol (Alc group), or physiological saline (NS group). The artery, portal vein and bile duct of the left lobe of the liver were clamped for 60 minutes and then released. At different time points after I/R, the rats were sacrificed and blood samples were collected to measure the levels of serum alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and NO. Hepatic tissue samples were collected for measuring endothelin expression by immunohistochemical staining and for routine morphological and histological examination. RESULTS: The levels of both ALT and LDH in the Mel group were significantly reduced for up to 24 hours after I/R compared with the Alc and NS groups (P<0.05). The levels of NO in the Mel group were significantly elevated for up to 12 hours after I/R relative to the NS group (P<0.05). The NO levels were also elevated at 0.5 and 6 hours after I/R in the Alc group (P<0.05). The immunohistochemical staining of hepatic tissue showedthat endothelin-positive cells were significantly fewer in the Mel group than in the Alc and NS groups at 6 hours after I/R (P<0.01). The necrosis of hepatocytes and the destruction of hepatic cords in the Alc and NS groups were greatly improved in Mel-treated rats, which is in concert with our functional data. CONCLUSIONS: Pretreatment with melatonin increased NO bioavailability and decreased endothelin expression, and consequently played a protective role in preserving both liver function and structure during ischemia and reperfusion injury.
文摘Objective: To explore the changes of plasma endothelin(ET) and nitric oxide (NO) levels in patients with a-cute pancreatitis.Methods: The level of plasma ET was measured by ra-dioactive-immunoassay, and NO by spectrophotometry.Results: The levels of ET, NO and the ET/NO ratioin patients with severe acute pancreatitis(SAP) within24 hours in hospital were all significantly higher thanthose in other groups of patients [(176±8)pg/ml,(97±11) μmol/L, and 1.83±0.12, P<0.01]. Com-pared to healthy controls(N), the levels of ET and NOin patients without pancreatitis acute abdomen (NAP)and patients with mild acute pancreatitis (MAP) in-creased significantly (P<0.01). After appropriate treat-ment, the levels of ET and NO in the MAP groupwere lower (P<0.01). Compared with those beforetreatment, the levels of ET and NO in the SAP groupon the 3rd and 7th day in hospital dropped signifi-cantly(P<0.01).The ET/NO ratio on the 7th daywas also lower than that on admission (P<0.01).Conclusions: The malfunction of endothelial cells andthe increased ET/NO ratio may be related to the mecha-nism of pancreatic microcirculatory disturbance in pa-tients with SAP; early dynamic determination of theseparameters may help predict the prognosis of SAP.
基金Supported by the National Natural Science Foundation of China,No. 30271254the Medical Development Foundation of Guangdong Province, No. 2004B35001005
文摘AIM： To investigate the perioperative changes of nitric oxide （NO） and endothelin （ET）, thromboxane A2 （TXA2） and prostaglandin （PGI2） during liver transplantation in end-stage liver disease patients. METHODS： Twenty-seven patients with end-stage cirrhosis undergoing liver transplantation were enrolled in this prospective study. Blood samples were obtained from superior vena at five different surgical stages. Plasma concentrations of nitrate and nitrite were determined to reflect plasma NO levels. Plasma levels of ET-1, 6-keto-PGF1 alpha and thromboxane B2 （TXB2）, the latter two being stable metabolites of PGI2 and TXA2 respectively, were measured.RESULTS： The NO level decreased significantly after vascular cross-clamping and increased significantly at 30 rain after reperfusion. While the ET levels at 30 rain after clamping and after reperfusion were significantly elevated. The ratio of NO/ET decreased significantly at 30 rain after vascular cross-clamping and at the end of surgery. The PGI2 level and the TXA2 during liver transplantation were significantly higher than the baseline level, but the ratio of TXA2/PGI2 decreased significantly at 30 rain after clamping. CONCLUSION： NO/ET and TXA2/PGI2 change during liver transplantation. Although the precise mechanism remains unknown, they may play a role in the pathobiology of a variety of liver transplant-relevant processes.
基金supported by the Key scientific and technological project in Qinghai Province,China (2006-N-143)
文摘Objective To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension(PAH) in patients of chronic obstructive pulmonary disease(COPD) associated with chronic cor pulmonale(CCP) during exacerbation.Methods Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group.The control group received standard treatment with antibiotics,antiasthmatic and expectorant medications,and oxygenation;and the ligustrazine treatment group received ligustrazine treatment(80 mg/d;i.v.;for 2 weeks) in addition to the standard treatment.Before and at the end of 2 week treatment,the clinic responses of the two regimens were evaluated,plasma levels of endothelin-1(ET-1) and nitric oxide(NO) were determined;arterial oxygen partial pressure(PaO_2),mean pulmonary arterial pressure(mPAP),outflow tract of right ventricle(RVOT),and internal diameter of right ventricle(RV) were measured.Results Good clinic benefits were achieved in both the standard and ligustrazine regimens,plasma level of ET-1,values of mPAP,RV and RVOT decreased significantly,plasma level of NO and PaO_2 values decreased(all P<0.01 vs pretreatment to all parameters).Compared with the control group,ligustrazine greatly enhanced the clinic efficacy from 77.1%to 97.1%(P<0.05),and also resulted in more significant changes of all these parameters(P<0.01 vs control group for all parameters).For both groups,the levels of plasma ET-1 were positively correlated with values of mPAP,RVOT,and RV(r = 0.710,0.853,and 0.766,respectively,all P = 0.000),and negatively correlated with plasma NO and PaO_2(r =- 0.823,and- 0.752,respectively,all P = 0.000).Conclusion Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area.The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells,thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.
基金funded by the grants from the National Technologies R&D Programme (2002BA518A04)
文摘[ Objective] To observe effect of Chanfukang on vascular endothelial cells of postpartum cows with Oi deficiency and Blood stasis, and to explore the treatment mechanism of Chanfukang. [Method] A total of 58 cows were assigned to four groups. The cows in group 1 and group 2 suffered from Qi deficiency and Blood stasis. The cows in group 1 were gavaged with Chanfukang （0.5 g/kg-BW, 5 d） at 12 h post partum, but the cows in group 2 were not treated. The cows in group 3 were healthy and gavaged with Chanfukang （0.4 g/kg.BW, 5 d） at 12 h post partum. Cows in group 4 were healthy control cows. The plasma endothelin （ET） concentration and serum nitric oxide （NO） concentration were determined before and after parturition, respectively. [ Result ] The plasma ET concentration and serum NO concentration were significantly higher in the cows with Qi deficiency and Blood stasis than in the healthy control cows （P 〈 0.05）. The NO concentration decreased on Day 10 post partum in the cows with Qi deficiency and Blood stasis, but it was still higher than that in the healthy control cows. After taking Chanfukang for 7 d, the ET concentration and NO concentration decreased, and no significant difference was found between the cows with Qi deficiency and Blood stasis treated with Chanfukang and the healthy control cows. [ Conclusion] Chanfukang may relieve Qi deficiency and Blood stasis of postpartum cows through decreasing plasma ET concentration and serum NO concentration.
文摘Objective: To observe the effect of purified Xuefu Capsule （PXC） on endothelin （ET） and nitric oxide synthetase （NOS） gene expression and proliferation of vascular smooth muscle cell （VSMC） in atherosclerotic rabbits. Methods: Molecular biological techniques of dot blot and in situ hybridization were adopted. Results: The expression of ET mRNA in atherosclerosis （AS）, plaques of the model group was higher,with the positive signals distributed mainly in arterial intimal AS plaques; while at the same time the expression in the PXC treated group was lower, with only few scattering signals found in arterial intimal AS plaques.NOS mRNA expression was less in the vascular wall of the AS model group, PXC could enhance NOS mRNA expression, positive signals could be found from intima to media. Conclusion: The effect of PXC on preventing and treating AS might be related to regulating the expression of ET mRNA and NOS mRNA in the vascular wall.
