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
Objective: To study the effect of simv astatin on mRNA expression of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10, after myocardial infarction (MI) in rats. Methods: The experimental rats were di...Objective: To study the effect of simv astatin on mRNA expression of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10, after myocardial infarction (MI) in rats. Methods: The experimental rats were di vided into three groups: Sham operation group (Sham), the rats were performed a left thoracotomy with no ligation of left descending coronary artery (LAD); Myoc ardial infarction control group (MI-C), the rats were performed a left thoracot omy with ligation of LAD; Simvastatin group (MI-S), the rats were performed a l eft thoracotomy with ligation of LAD, and given simvastatin 40 mg/kg body weight per day through gavage, while the other two groups were given equal normal sali ne by gavage. All animals were caged to feed four weeks. After finished, the rat s were killed, and the hearts were harvested and cut into two equal parts at the level of the papillary muscle: one was used to determine mRNA expression of myo cardial cytokines by RT-PCR, and the other was used to measure cytokines by Wes tern blotting and immunohistochemical staining. Results: All the pro-inflammatory cytokines mentioned above showed few expression in Sham opera tion group. In the MI groups (including MI-C and MI-S groups), mRNA expression of each of these cytokines markedly increased compared with the Sham operation group (P<0.01). Compared with MI-C group, the mRNA expression of TNF- α, IL-1β and IL-6 in the MI-S group significant ly reduced (P<0.01), and mRNA expression of IL-10 obviously increased ( P<0.01). Cytokines principally located in cardiomyocytes of non-infarcted ar ea and survived cardiomyocytes of infarcted area, simvastatin could decrease TNF -α, IL-1β, and IL-6 and increase IL-10 by confirmation of immunohistochemical staining. Conclusion: Simvas tatin markedly lowers pro-inflammatory cytokines, and increases inflammatory pr otective cytokine. Its mechanism needs to be elucidated.展开更多
Objective To investigate the influence of ischemic reperfusion and ischemic preconditioning on the cardiac structure and function and markers of myocardial injury, especialy on the heine oxygenase-1/carbon monoxide HO...Objective To investigate the influence of ischemic reperfusion and ischemic preconditioning on the cardiac structure and function and markers of myocardial injury, especialy on the heine oxygenase-1/carbon monoxide HO-1/CO reactive system. Methods Mode of langendorff was used in isolated rat hearts with retrograde perfusion. Ischemic reperfusion protocol: perfusion for 60 minutes, stopping perfusion for 30 minutes and reperfusion for 30 minutes. Ischemic preconditioning protocol: perfusion for 30 minutes, stopping perfusion for 5 minutes and reperfusion for 5 minutes and repeating three times, stopping perfusion for 30 minutes and reperfusion for 30 minutes. Control protocol: perfusion 120minutes. HO-1 enzyme activity and HbCO levels in myocardium of each group were measured at reperfusion 30minutes. The HO-1 mRNA and protein expression in rat left ventricular myocardium after reperfusion 30 min were examined by RT-PCR and werstern blotting and immunohistochemistry. Indexes of Cardiac Function were recorded in control group, ischemia and reperfusion group(IR) and ischemic preconditioning group (IPC). Indexes of cardiac injury and cardiac oxidative activity were examined. The changes of myocardial structure were checked up by electron microscopy. Results At reperfusion 30min, the indexes of cardiac function in IPC group were significantly higher than that in IR group (P<0.01), but lower than that in control group(P<0.05) and recovery percentage of cardiac function showed the same changes. The activity of HO-1 and the contents of HbCO in myocardium were increased significantly in IR and IPC(P<0.01), but that of IPC were higher (P<0.01). The expression of HO-1 mRNA and Protein in myocardium were also increased significantly in IR and IPC (P<0.01),but that of IPC were higher (P<0.01). The contents of LDH and total CK and MDA were significantly decreased in IPC Compared to IR (P<0.01) and the activity of SOD were increased remarkably in IPC (P<0.01) and there were differnce betwecn IR and IPC (P<0.01). The localization of HO-1 protein expression in myocardium of rat hearts showed intense staining in the interstitial spaces and perivascular region of blood vessel and moderate staining in the cardiomyocytes and endocardium in IPC and IR, but IPC was more distinct. The myocardial structure injury in IR were the most grievous and the injury were significantly recoveried in IPC. Conclusion The activity of endogenous HO-1/CO reactive system were significantly higher in ischemic reperfusion and preconditioning of isolated rat hearts and might be related with cardiac protection induced by ischemic reperfusion.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Grant support:National Natural Science Foundation (30370574)Henan Province’Creation Talent Projection of Medical Science & Technology (2002116)Zhengzhou University’Scientific Research Development Fund (2004021).
文摘Objective: To study the effect of simv astatin on mRNA expression of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10, after myocardial infarction (MI) in rats. Methods: The experimental rats were di vided into three groups: Sham operation group (Sham), the rats were performed a left thoracotomy with no ligation of left descending coronary artery (LAD); Myoc ardial infarction control group (MI-C), the rats were performed a left thoracot omy with ligation of LAD; Simvastatin group (MI-S), the rats were performed a l eft thoracotomy with ligation of LAD, and given simvastatin 40 mg/kg body weight per day through gavage, while the other two groups were given equal normal sali ne by gavage. All animals were caged to feed four weeks. After finished, the rat s were killed, and the hearts were harvested and cut into two equal parts at the level of the papillary muscle: one was used to determine mRNA expression of myo cardial cytokines by RT-PCR, and the other was used to measure cytokines by Wes tern blotting and immunohistochemical staining. Results: All the pro-inflammatory cytokines mentioned above showed few expression in Sham opera tion group. In the MI groups (including MI-C and MI-S groups), mRNA expression of each of these cytokines markedly increased compared with the Sham operation group (P<0.01). Compared with MI-C group, the mRNA expression of TNF- α, IL-1β and IL-6 in the MI-S group significant ly reduced (P<0.01), and mRNA expression of IL-10 obviously increased ( P<0.01). Cytokines principally located in cardiomyocytes of non-infarcted ar ea and survived cardiomyocytes of infarcted area, simvastatin could decrease TNF -α, IL-1β, and IL-6 and increase IL-10 by confirmation of immunohistochemical staining. Conclusion: Simvas tatin markedly lowers pro-inflammatory cytokines, and increases inflammatory pr otective cytokine. Its mechanism needs to be elucidated.
文摘Objective To investigate the influence of ischemic reperfusion and ischemic preconditioning on the cardiac structure and function and markers of myocardial injury, especialy on the heine oxygenase-1/carbon monoxide HO-1/CO reactive system. Methods Mode of langendorff was used in isolated rat hearts with retrograde perfusion. Ischemic reperfusion protocol: perfusion for 60 minutes, stopping perfusion for 30 minutes and reperfusion for 30 minutes. Ischemic preconditioning protocol: perfusion for 30 minutes, stopping perfusion for 5 minutes and reperfusion for 5 minutes and repeating three times, stopping perfusion for 30 minutes and reperfusion for 30 minutes. Control protocol: perfusion 120minutes. HO-1 enzyme activity and HbCO levels in myocardium of each group were measured at reperfusion 30minutes. The HO-1 mRNA and protein expression in rat left ventricular myocardium after reperfusion 30 min were examined by RT-PCR and werstern blotting and immunohistochemistry. Indexes of Cardiac Function were recorded in control group, ischemia and reperfusion group(IR) and ischemic preconditioning group (IPC). Indexes of cardiac injury and cardiac oxidative activity were examined. The changes of myocardial structure were checked up by electron microscopy. Results At reperfusion 30min, the indexes of cardiac function in IPC group were significantly higher than that in IR group (P<0.01), but lower than that in control group(P<0.05) and recovery percentage of cardiac function showed the same changes. The activity of HO-1 and the contents of HbCO in myocardium were increased significantly in IR and IPC(P<0.01), but that of IPC were higher (P<0.01). The expression of HO-1 mRNA and Protein in myocardium were also increased significantly in IR and IPC (P<0.01),but that of IPC were higher (P<0.01). The contents of LDH and total CK and MDA were significantly decreased in IPC Compared to IR (P<0.01) and the activity of SOD were increased remarkably in IPC (P<0.01) and there were differnce betwecn IR and IPC (P<0.01). The localization of HO-1 protein expression in myocardium of rat hearts showed intense staining in the interstitial spaces and perivascular region of blood vessel and moderate staining in the cardiomyocytes and endocardium in IPC and IR, but IPC was more distinct. The myocardial structure injury in IR were the most grievous and the injury were significantly recoveried in IPC. Conclusion The activity of endogenous HO-1/CO reactive system were significantly higher in ischemic reperfusion and preconditioning of isolated rat hearts and might be related with cardiac protection induced by ischemic reperfusion.