Objective: Previous studies have shown t hat allitridum can protect myocardium from ischemia/reperfusion (I/R) injury, bu t whether allitridum had the effect of anti-apoptosis is unclear. The aim of th is study was t...Objective: Previous studies have shown t hat allitridum can protect myocardium from ischemia/reperfusion (I/R) injury, bu t whether allitridum had the effect of anti-apoptosis is unclear. The aim of th is study was to investigate whether allitridum had the effects of pharmacologica l preconditioning and decreasing myocardium apoptosis after ischemic insult. Methods: Pentobarbital sodium-anesthetized Sprague-Dawley (SD) rats underwent 30 min of left anterior descending (LAD) coronary occlusion foll owed by 120 min of reperfusion. Thirty-six rats were divided into three groups randomly: Control group, I/R group and allitridum (G) group. The control and I/R groups with saline, G group with allitridum were administrated 24 h before oper ation. Control group underwent only sham operation; the other two groups underwe nt I/R operation. Infarcted size (IS/AAR %) was measured in I/R and G groups. Ma londialdehyde (MDA), Creatine kinase isoenzyme-MB (CK-MB ), Superoxide dismuta se (SOD)and the apoptosis index (AI) by TUNEL staining were measured in each gro up. In addition, DNA fragmentation by agarose gel electrophoresis was conducted on DNA isolated from these groups. Results: Allitridum p retreatm ent decreased the infarcted size compared with I/R group in IS/ AAR%[(21.85±1. 49)% vs. ( 44.65±4.65)%, P<0.01], CK-MB [(986.40±94.01) vs. (2044.2 5±1 07.28) U/L, P<0.01] and MDA [(3.26±0.35) vs. (4.96±0.46) nmol/mg pro, P<0.01], and SOD level in G group was higher than that of I/R group [(140 .20±12.89)vs. (73.16±11.22) U/mg pro, P<0.01]. AI of I/R group was highe r than that of G group [(13.99±3.05)% vs. (6.97±1.23)%, P<0.01], which was consistent with that in DNA fragmentation by agarose gel electrophoresis. Conclusion: This study indicated that allitridum had the effect of protecting myocardium against I/R injury and decreasing infarcted zone. The e ffect was probably through decreasing myocardium apoptosis in I/R injury.展开更多
Intracellular calcium overload is a key factor for myocardial ischemia reperfusion injury（IR）. However, there was no report for interstitial calcium concentration dynamics. We investigated the interstitial calcium d...Intracellular calcium overload is a key factor for myocardial ischemia reperfusion injury（IR）. However, there was no report for interstitial calcium concentration dynamics. We investigated the interstitial calcium dynamics in rat myocardial IR model in vivo. A microdialysis system was involved, and the time delay of the system and recovery time was introduced and tested with a fluids switching method. Twelve SD rats were divided into IR or control group. Myocardial IR was induced by ligating（20 min） then releasing（60 min） the suture underlying left anterior descending branch. Mycrodialyisis probe was implanted into the left ventricular myocardium perfusion area for occlusion. Dialysate samples were collected every 10 min. Dialysate calcium concentration was detected with an atomic absorption spectrophotometer. Recovery time for the microdialysis system was 20 min, and recovery rate was 16%. Dialysate calcium concentration showed no changes during ischemia, descended immediately after reperfusion, reached the lowest level（67% of baseline value） 20 min after reperfusion, then escalated slowly. Recovery time was an important parameter for mycrodialysis technique, and it should not be neglected and needed to be tested. Our data suggest that interstitial calcium concentration in rats with myocardial IR in vivo kept steady in ischemia, descended rapidly at the initial reperfusion, then rebounded slowly. In conclusion, we introduced the concept of recovery time for microdialysis and provided a simple testing method.展开更多
Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the c...Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, Ad. VEGF-B, Ad. LacZ or PBS were administrated directly into the myocardium at 10 sites in the circumflex distribution (109 PFU or 100 μl) according to groups. Echocardiography and ex vivo coronary angiography were performed. The injection sites around myocardium were harvested and subjected to histological analysis and immunochemical staining. Results: E-chocardiography assessment 4 weeks after vector administration demonstrated significant improvement of regional wall systolic function. Collateral vessel development assessed by angiography was also significantly greater in Ad. VEGF-B animals than that in control animals. Vascular density analysis revealed a mean of 43±5 neovessels per high-power field in Ad. VEGF-B group versus 19±4 and 17±6展开更多
Objective To elucidate whether endoxin is one of important factors involved in myocardial ischemia reperfusion (MIR) injury, the change of myocardial endoxin level was determined in rats with MIR injury model and the ...Objective To elucidate whether endoxin is one of important factors involved in myocardial ischemia reperfusion (MIR) injury, the change of myocardial endoxin level was determined in rats with MIR injury model and the effects of anti-digoxin antiserum (ADA), an endoxin specific antagonist, on MIR injury were studied. Methods MIR injury model was obtained by ligating left anterior descending coronary artery 30 min followed by 45 min reperfusion. Sprauge Dawley rats were randomly divided into six groups of 10 rats, each. Sham group, MIR group, normal saline group, ADA 9, 18 and 36 mg/kg. ECG was continuously recorded. After reperfusion left ventricular myocardium samples of ischemic area were processed immediately. Myocardial endoxin level, Na++/K++-ATPase, Ca+{2+}-ATPase, Mg+{2+}-ATPase activities, and intramitochondrial Ca+{2+} content were measured. Results Myocardial endoxin level was significantly increased; Na++/K++-ATPase, Ca+{2+}- ATPase , and Mg+{2+}-ATPase activities were remarkably decreased; intramitochondrial Ca+{2+} content was remarkably raised; ST segments of ECG were significantly elevated and occurrence and scores of ventricular arrhythmias were significantly increased in early stage of reperfusion in rats with MIR. In all groups with ADA, myocardial endoxin level was remarkably decreased; Na++/K++-ATPase, Ca+{2+}-ATPase and Mg+{2+}-ATPase activities were drastically increased; intramitochondrial Ca+{2+} content was declined; ST segments and ventricular arrhythmias were improved. Conclusion Myocardial endoxin level was increased in MIR, which implies that the elevated endoxin may be one of major factors inducing MIR injury. This postulate is supported by the observation that ADA has protective and therapeutic effects against MIR injury probably by antagonizing the action of endoxin. The underlying mechanism may be ascribed to restoration of energy metabolism, and attenuation of intracellular Ca+{2+} overload.展开更多
文摘Objective: Previous studies have shown t hat allitridum can protect myocardium from ischemia/reperfusion (I/R) injury, bu t whether allitridum had the effect of anti-apoptosis is unclear. The aim of th is study was to investigate whether allitridum had the effects of pharmacologica l preconditioning and decreasing myocardium apoptosis after ischemic insult. Methods: Pentobarbital sodium-anesthetized Sprague-Dawley (SD) rats underwent 30 min of left anterior descending (LAD) coronary occlusion foll owed by 120 min of reperfusion. Thirty-six rats were divided into three groups randomly: Control group, I/R group and allitridum (G) group. The control and I/R groups with saline, G group with allitridum were administrated 24 h before oper ation. Control group underwent only sham operation; the other two groups underwe nt I/R operation. Infarcted size (IS/AAR %) was measured in I/R and G groups. Ma londialdehyde (MDA), Creatine kinase isoenzyme-MB (CK-MB ), Superoxide dismuta se (SOD)and the apoptosis index (AI) by TUNEL staining were measured in each gro up. In addition, DNA fragmentation by agarose gel electrophoresis was conducted on DNA isolated from these groups. Results: Allitridum p retreatm ent decreased the infarcted size compared with I/R group in IS/ AAR%[(21.85±1. 49)% vs. ( 44.65±4.65)%, P<0.01], CK-MB [(986.40±94.01) vs. (2044.2 5±1 07.28) U/L, P<0.01] and MDA [(3.26±0.35) vs. (4.96±0.46) nmol/mg pro, P<0.01], and SOD level in G group was higher than that of I/R group [(140 .20±12.89)vs. (73.16±11.22) U/mg pro, P<0.01]. AI of I/R group was highe r than that of G group [(13.99±3.05)% vs. (6.97±1.23)%, P<0.01], which was consistent with that in DNA fragmentation by agarose gel electrophoresis. Conclusion: This study indicated that allitridum had the effect of protecting myocardium against I/R injury and decreasing infarcted zone. The e ffect was probably through decreasing myocardium apoptosis in I/R injury.
基金supported by grants from the National Natural Science Foundation of China(No.81371714)the Natural Science Foundation of Guangdong Province(No.S2012010008151)
文摘Intracellular calcium overload is a key factor for myocardial ischemia reperfusion injury（IR）. However, there was no report for interstitial calcium concentration dynamics. We investigated the interstitial calcium dynamics in rat myocardial IR model in vivo. A microdialysis system was involved, and the time delay of the system and recovery time was introduced and tested with a fluids switching method. Twelve SD rats were divided into IR or control group. Myocardial IR was induced by ligating（20 min） then releasing（60 min） the suture underlying left anterior descending branch. Mycrodialyisis probe was implanted into the left ventricular myocardium perfusion area for occlusion. Dialysate samples were collected every 10 min. Dialysate calcium concentration was detected with an atomic absorption spectrophotometer. Recovery time for the microdialysis system was 20 min, and recovery rate was 16%. Dialysate calcium concentration showed no changes during ischemia, descended immediately after reperfusion, reached the lowest level（67% of baseline value） 20 min after reperfusion, then escalated slowly. Recovery time was an important parameter for mycrodialysis technique, and it should not be neglected and needed to be tested. Our data suggest that interstitial calcium concentration in rats with myocardial IR in vivo kept steady in ischemia, descended rapidly at the initial reperfusion, then rebounded slowly. In conclusion, we introduced the concept of recovery time for microdialysis and provided a simple testing method.
基金Supported by the National Natural Science Foundation of China (No. 39970735)
文摘Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, Ad. VEGF-B, Ad. LacZ or PBS were administrated directly into the myocardium at 10 sites in the circumflex distribution (109 PFU or 100 μl) according to groups. Echocardiography and ex vivo coronary angiography were performed. The injection sites around myocardium were harvested and subjected to histological analysis and immunochemical staining. Results: E-chocardiography assessment 4 weeks after vector administration demonstrated significant improvement of regional wall systolic function. Collateral vessel development assessed by angiography was also significantly greater in Ad. VEGF-B animals than that in control animals. Vascular density analysis revealed a mean of 43±5 neovessels per high-power field in Ad. VEGF-B group versus 19±4 and 17±6
文摘Objective To elucidate whether endoxin is one of important factors involved in myocardial ischemia reperfusion (MIR) injury, the change of myocardial endoxin level was determined in rats with MIR injury model and the effects of anti-digoxin antiserum (ADA), an endoxin specific antagonist, on MIR injury were studied. Methods MIR injury model was obtained by ligating left anterior descending coronary artery 30 min followed by 45 min reperfusion. Sprauge Dawley rats were randomly divided into six groups of 10 rats, each. Sham group, MIR group, normal saline group, ADA 9, 18 and 36 mg/kg. ECG was continuously recorded. After reperfusion left ventricular myocardium samples of ischemic area were processed immediately. Myocardial endoxin level, Na++/K++-ATPase, Ca+{2+}-ATPase, Mg+{2+}-ATPase activities, and intramitochondrial Ca+{2+} content were measured. Results Myocardial endoxin level was significantly increased; Na++/K++-ATPase, Ca+{2+}- ATPase , and Mg+{2+}-ATPase activities were remarkably decreased; intramitochondrial Ca+{2+} content was remarkably raised; ST segments of ECG were significantly elevated and occurrence and scores of ventricular arrhythmias were significantly increased in early stage of reperfusion in rats with MIR. In all groups with ADA, myocardial endoxin level was remarkably decreased; Na++/K++-ATPase, Ca+{2+}-ATPase and Mg+{2+}-ATPase activities were drastically increased; intramitochondrial Ca+{2+} content was declined; ST segments and ventricular arrhythmias were improved. Conclusion Myocardial endoxin level was increased in MIR, which implies that the elevated endoxin may be one of major factors inducing MIR injury. This postulate is supported by the observation that ADA has protective and therapeutic effects against MIR injury probably by antagonizing the action of endoxin. The underlying mechanism may be ascribed to restoration of energy metabolism, and attenuation of intracellular Ca+{2+} overload.
