AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis an...AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats. METHODS： Thirty-eight female Wistar rats were used. Acute pancreatitis （AP） was induced by two i.p. injections of caerulein at 2-h intervals （at a total dose of 100 μg/kg b.wt）. The other two groups received additional melatonin （20 mg/kg b.wt） or an antioxidant mixture containing L（＋）-ascorbic acid （14.3 mg/kb.wt.） and N-acetyl cysteine （181 mg/kg b.wt.） i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde （MDA） and changes in tissue antioxidant enzyme levels, catalase （CAT） and glutathione peroxidase （GPx）. Histopathological examination was performed using scoring systems. RESULTS： The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein＋melatonin （P= 0.001）, and careulein and caerulein ＋ L（＋）- ascorbic acid ＋N-acetyl cysteine groups （P= 0.002）. The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein ＋ melatonin （P=0.004）, and careulein and caerulein ＋ L（＋）-ascorbic acid ＋N-acetyl cysteine groups （P=0.002）. Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels （P= 0.01, P= 0.003, respectively） whereas a significant decrease in CAT （P= 0.002, P=0.003, respectively） and GPx activities （P= 0.002, P= 0.03, respectively）. Melatonin and L（＋）-ascorbic acid ＋N-acetyl cysteine administration significantly decreased MDA levels in pancreas （P= 0.03, P= 0.002, respectively） and liver （P= 0.007, P= 0.01, respectively）. Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT （P= 0.002, P= 0.001, respectively） and GPx activities （P=0.002, P=0.001）. Additionally, L（＋）-ascorbic acid＋N-acetyl cysteine significantly increased pancreatic GPx （P= 0.002） and hepatic CAT and GPx activities （P= 0.001, P= 0.007, respectively） CONCLUSION： Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid＋N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.展开更多
Objective To examine the effects of exogenously administered intermedin （IMD,adrenomedullin-2） on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive ra...Objective To examine the effects of exogenously administered intermedin （IMD,adrenomedullin-2） on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats （SHRs） as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto （WKY） group （n =12）,SHR group （n =12）,IMD group （SHRs infused with IMD 1-47 500 ng/kg per hour,n =12）,and ADM group （SHRs infused with adrenomedullin 500 ng/kg per hour,n =12）.Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development （LV ± dp/dtmax）,left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins （RAMP1 and RAMP2）,aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor （CRLR）;suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide （ANP） and myocardial brain natriuretic peptide （BNP）.Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.展开更多
AIM： To investigate the influence of remote ischemic preconditioning （RIPC） on anastomotic integrity. METHODS： Sixty male Wistar rats were randomized to six groups. The control group （n = 10） had an end- to-end ...AIM： To investigate the influence of remote ischemic preconditioning （RIPC） on anastomotic integrity. METHODS： Sixty male Wistar rats were randomized to six groups. The control group （n = 10） had an end- to-end ileal anastomosis without RIPC. The preconditioned groups （n = 34） varied in time of ischemia and time of reperfusion. One group received the amino acid L-arginine before constructing the anastomosis （n = 9）. On postoperative day 4, the rats were re-laparotomized, and bursting pressure, hydroxyproline concentration, intra-abdominal adhesions, and a histological score concerning the mucosat ischemic injury were collected. The data are given as median （range）.RESULTS： On postoperative day 4, median bursting pressure was 124 mmHg （60-146 mmHg） in the control group. The experimental groups did not show a statistically significant difference （P 〉 0.05）. Regarding the hydroxyproline concentration, we did not find any significant variation in the experimental groups. We detected significantly less mucosal injury in the RIPC groups. Furthermore, we assessed more extensive intra-abdominal adhesions in the preconditioned groups than in the control group. CONCLUSION： RIPC directly before performing small bowel anastomosis does not affect anastomotic stability in the early period, as seen in ischemic preconditioning.展开更多
Objective To investigate the effects of captopril on cardiac function and levels of energy-rich phosphates in pressure overload induced left ventricular hypertrophy rats. Methods One hundred and twenty SD rats were ra...Objective To investigate the effects of captopril on cardiac function and levels of energy-rich phosphates in pressure overload induced left ventricular hypertrophy rats. Methods One hundred and twenty SD rats were randomly divided into three groups： sham operation group （SH group, n=40）,coarctation of abdominal aorta group （CAA group, n=40） and captopril treatment lmg~ 100g1 ~ d-1） group （CAP group, n=40）. Left ventricular end-diastolic pressure （LVEDP）, left venh-icular mass index （LVMI）, levels of energy-rich phosphates and morphological changes of the myocardial mitochondria were compared at the 62 and 82 week after operation. Results At 62 week, in CAA group, LVMI and LVEDP were increased and _ dp/dtmax was decreased, while ATP and ADP were decreased and AMP was increased （P〈0.01）. These changes were much obvious at 8th week （P〈0.01）. Compared with those of CAA group, the parameters of heart function and energy-rich phosphates （ATP, ADP, AMP, TAN） in CAP group were improved significantly（P〈0.01） at the 6th and 8th week. In CAP group, the parameters of heart function and energy-rich phosphates （ADP, AMP, TAN） were much better at 8~ week than those at 6th week. The morphological change of mitochondria was less in CAP group than that in CAA group. Conclusion Captopril significantly improves myocardial energy metabolism in pressure overload rats and protects the function of myocardial mitochondria展开更多
Objective To clarify whether the disturbances in metabolic kinetics of the essential aminoacid, phenylalanine (phe), are implicated in the genetic pathogenesis of essential hypertension (EH).Methods 1. L-(2, 3D3)-le...Objective To clarify whether the disturbances in metabolic kinetics of the essential aminoacid, phenylalanine (phe), are implicated in the genetic pathogenesis of essential hypertension (EH).Methods 1. L-(2, 3D3)-leucine, L-(2, 3D3)-isoleucine, L-15N-lysine, L-(2, 3D3)-valine and L-(2, 3D3)-phe were used for simultaneously studying comparative metabolic kinetics using stable isotope tracer methods with a GC-MS system. Study groups were the offspring with both parents suffering EH (n=10, FH+), 2 or more than 2 parents and grand-parents with EH and stroke (n=12, FS+) and those without genetic predisposition of EH and stroke (n=12, F) groups. 2. By comparing the radioactive counts of ［3H］-phe, and their weight transformation in blood after 1.5?Ci/kg i.v. administration at defined intervals and in tissues obtained after being sacrified among spontaneously hypertensive rats (SHR), 2 kidney-1 clip hypertensive rats (2K1C) and their normotensive controls (WKY). 3. The time transport and concentration transport of ［3H］-L-phe in cpm between the cultured vascular smooth muscle cell of 5th generation in SHR and WKY were compared.Results A single and unique disturbance of metabolic kinetics in phe were found in FH+, FS+ and SHR. The plasma pool or apparent volume of distribution was enlarged, and the turnover rate constants between plasma and cell tended to show a decrease. The pharmacokinetics of phe in 2K1C was not changed. Only phe content in heart and aorta, the vital organs for predicting BP, were higher in SHR than in WKY tissues studied. Both the time and concentration transport were higher in SHR, e.g., an increment in the net-uptake of L-phe by vascular tissue.Conclusion A unique aberrant of metabolic kinetics of phe might be implicated in the inherited pathogenesis of EH and stroke both from clinical and animal studies.展开更多
Objective: To investigate the specificity of the effects of electroacupuncture (EA) at different acupoints on gastric functional activity and gastric blood flow after colorectal distension (CRD) in the rat. Methods: F...Objective: To investigate the specificity of the effects of electroacupuncture (EA) at different acupoints on gastric functional activity and gastric blood flow after colorectal distension (CRD) in the rat. Methods: Fifty Wistar rats were randomly divided into 5 groups: a control group, a Zusanli group, a non-point group, a Taichong group and a Neiguan group. Rats were anesthetized after 18 h of fasting, and a rat model of nociceptive blood pressure elevation and abnormal electrogastrogram (EGG) and gastric tension (GT) was prepared by gasbag-induced CRD. EA was given bilaterally, and its effects on gastric blood flow (GBF) of the arcus vasculosi of the greater omentum, blood pressure, EGG fast wave properties, and gastric smooth muscle tension (GT) were quantified. Results: CRD induced an increase in blood pressure that was significantly inhibited by EA at all points (all P<0.05), and the inhibitory effects were greater in the Zusanli and Neiguan groups compared to the non-point group (both P<0.05). CRD also caused reductions in GT and GBF, and in the amplitude, frequency and duration of EGG waves (all P<0.05). These effects were also reversed by EA. The effects of EA on EGG wave amplitude, GT, and GBF were superior in the Zusanli group compared to the Taichong group, Neiguan group, and the non-point group. Conclusion: EA significantly counteracted CRD-induced changes in blood pressure, GBF, EGG, and GT. The effects of stimulation at Zusanli (ST 36) were significantly greater compared to other points, indicating relative specificity of this acupoint.展开更多
文摘AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats. METHODS： Thirty-eight female Wistar rats were used. Acute pancreatitis （AP） was induced by two i.p. injections of caerulein at 2-h intervals （at a total dose of 100 μg/kg b.wt）. The other two groups received additional melatonin （20 mg/kg b.wt） or an antioxidant mixture containing L（＋）-ascorbic acid （14.3 mg/kb.wt.） and N-acetyl cysteine （181 mg/kg b.wt.） i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde （MDA） and changes in tissue antioxidant enzyme levels, catalase （CAT） and glutathione peroxidase （GPx）. Histopathological examination was performed using scoring systems. RESULTS： The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein＋melatonin （P= 0.001）, and careulein and caerulein ＋ L（＋）- ascorbic acid ＋N-acetyl cysteine groups （P= 0.002）. The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein ＋ melatonin （P=0.004）, and careulein and caerulein ＋ L（＋）-ascorbic acid ＋N-acetyl cysteine groups （P=0.002）. Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels （P= 0.01, P= 0.003, respectively） whereas a significant decrease in CAT （P= 0.002, P=0.003, respectively） and GPx activities （P= 0.002, P= 0.03, respectively）. Melatonin and L（＋）-ascorbic acid ＋N-acetyl cysteine administration significantly decreased MDA levels in pancreas （P= 0.03, P= 0.002, respectively） and liver （P= 0.007, P= 0.01, respectively）. Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT （P= 0.002, P= 0.001, respectively） and GPx activities （P=0.002, P=0.001）. Additionally, L（＋）-ascorbic acid＋N-acetyl cysteine significantly increased pancreatic GPx （P= 0.002） and hepatic CAT and GPx activities （P= 0.001, P= 0.007, respectively） CONCLUSION： Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid＋N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.
文摘Objective To examine the effects of exogenously administered intermedin （IMD,adrenomedullin-2） on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats （SHRs） as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto （WKY） group （n =12）,SHR group （n =12）,IMD group （SHRs infused with IMD 1-47 500 ng/kg per hour,n =12）,and ADM group （SHRs infused with adrenomedullin 500 ng/kg per hour,n =12）.Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development （LV ± dp/dtmax）,left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins （RAMP1 and RAMP2）,aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor （CRLR）;suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide （ANP） and myocardial brain natriuretic peptide （BNP）.Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.
基金Supported by Science Fund of the Department for General and Visceral Surgery at the University of Freiburg
文摘AIM： To investigate the influence of remote ischemic preconditioning （RIPC） on anastomotic integrity. METHODS： Sixty male Wistar rats were randomized to six groups. The control group （n = 10） had an end- to-end ileal anastomosis without RIPC. The preconditioned groups （n = 34） varied in time of ischemia and time of reperfusion. One group received the amino acid L-arginine before constructing the anastomosis （n = 9）. On postoperative day 4, the rats were re-laparotomized, and bursting pressure, hydroxyproline concentration, intra-abdominal adhesions, and a histological score concerning the mucosat ischemic injury were collected. The data are given as median （range）.RESULTS： On postoperative day 4, median bursting pressure was 124 mmHg （60-146 mmHg） in the control group. The experimental groups did not show a statistically significant difference （P 〉 0.05）. Regarding the hydroxyproline concentration, we did not find any significant variation in the experimental groups. We detected significantly less mucosal injury in the RIPC groups. Furthermore, we assessed more extensive intra-abdominal adhesions in the preconditioned groups than in the control group. CONCLUSION： RIPC directly before performing small bowel anastomosis does not affect anastomotic stability in the early period, as seen in ischemic preconditioning.
基金Corresponding author： Dr. Cao Xuebin, MD, Department of Cardiology, 252 Hospital of Chinese PLA, Baoding 071000,Hebei Province,China Email： cxb252@yahoo.com.cn. This study was supported by the National Natural Science Foundation of China （30873398）, Research Project of ＂Eleventh Five-year Plan＂ for Medical Science Development of PLA（2006MA064） and the Research Project of Hebei Province （06276012D- 114）.
文摘Objective To investigate the effects of captopril on cardiac function and levels of energy-rich phosphates in pressure overload induced left ventricular hypertrophy rats. Methods One hundred and twenty SD rats were randomly divided into three groups： sham operation group （SH group, n=40）,coarctation of abdominal aorta group （CAA group, n=40） and captopril treatment lmg~ 100g1 ~ d-1） group （CAP group, n=40）. Left ventricular end-diastolic pressure （LVEDP）, left venh-icular mass index （LVMI）, levels of energy-rich phosphates and morphological changes of the myocardial mitochondria were compared at the 62 and 82 week after operation. Results At 62 week, in CAA group, LVMI and LVEDP were increased and _ dp/dtmax was decreased, while ATP and ADP were decreased and AMP was increased （P〈0.01）. These changes were much obvious at 8th week （P〈0.01）. Compared with those of CAA group, the parameters of heart function and energy-rich phosphates （ATP, ADP, AMP, TAN） in CAP group were improved significantly（P〈0.01） at the 6th and 8th week. In CAP group, the parameters of heart function and energy-rich phosphates （ADP, AMP, TAN） were much better at 8~ week than those at 6th week. The morphological change of mitochondria was less in CAP group than that in CAA group. Conclusion Captopril significantly improves myocardial energy metabolism in pressure overload rats and protects the function of myocardial mitochondria
基金ThisstudywassupportedbythegrantoftheNationalNaturalSciencesFoundationofChina (No 391735 0 No 39470 62 6)
文摘Objective To clarify whether the disturbances in metabolic kinetics of the essential aminoacid, phenylalanine (phe), are implicated in the genetic pathogenesis of essential hypertension (EH).Methods 1. L-(2, 3D3)-leucine, L-(2, 3D3)-isoleucine, L-15N-lysine, L-(2, 3D3)-valine and L-(2, 3D3)-phe were used for simultaneously studying comparative metabolic kinetics using stable isotope tracer methods with a GC-MS system. Study groups were the offspring with both parents suffering EH (n=10, FH+), 2 or more than 2 parents and grand-parents with EH and stroke (n=12, FS+) and those without genetic predisposition of EH and stroke (n=12, F) groups. 2. By comparing the radioactive counts of ［3H］-phe, and their weight transformation in blood after 1.5?Ci/kg i.v. administration at defined intervals and in tissues obtained after being sacrified among spontaneously hypertensive rats (SHR), 2 kidney-1 clip hypertensive rats (2K1C) and their normotensive controls (WKY). 3. The time transport and concentration transport of ［3H］-L-phe in cpm between the cultured vascular smooth muscle cell of 5th generation in SHR and WKY were compared.Results A single and unique disturbance of metabolic kinetics in phe were found in FH+, FS+ and SHR. The plasma pool or apparent volume of distribution was enlarged, and the turnover rate constants between plasma and cell tended to show a decrease. The pharmacokinetics of phe in 2K1C was not changed. Only phe content in heart and aorta, the vital organs for predicting BP, were higher in SHR than in WKY tissues studied. Both the time and concentration transport were higher in SHR, e.g., an increment in the net-uptake of L-phe by vascular tissue.Conclusion A unique aberrant of metabolic kinetics of phe might be implicated in the inherited pathogenesis of EH and stroke both from clinical and animal studies.
基金supported by TCM Item of National Key Basic Study (2005CB523306, 2006CB504506 2007CB512505)the National Natural Science Foundation of China (30973796, 90709031)
文摘Objective: To investigate the specificity of the effects of electroacupuncture (EA) at different acupoints on gastric functional activity and gastric blood flow after colorectal distension (CRD) in the rat. Methods: Fifty Wistar rats were randomly divided into 5 groups: a control group, a Zusanli group, a non-point group, a Taichong group and a Neiguan group. Rats were anesthetized after 18 h of fasting, and a rat model of nociceptive blood pressure elevation and abnormal electrogastrogram (EGG) and gastric tension (GT) was prepared by gasbag-induced CRD. EA was given bilaterally, and its effects on gastric blood flow (GBF) of the arcus vasculosi of the greater omentum, blood pressure, EGG fast wave properties, and gastric smooth muscle tension (GT) were quantified. Results: CRD induced an increase in blood pressure that was significantly inhibited by EA at all points (all P<0.05), and the inhibitory effects were greater in the Zusanli and Neiguan groups compared to the non-point group (both P<0.05). CRD also caused reductions in GT and GBF, and in the amplitude, frequency and duration of EGG waves (all P<0.05). These effects were also reversed by EA. The effects of EA on EGG wave amplitude, GT, and GBF were superior in the Zusanli group compared to the Taichong group, Neiguan group, and the non-point group. Conclusion: EA significantly counteracted CRD-induced changes in blood pressure, GBF, EGG, and GT. The effects of stimulation at Zusanli (ST 36) were significantly greater compared to other points, indicating relative specificity of this acupoint.
