AIM： TO investigate the effect of E3-methyl-l-phe- nyl-2-pyrazolin-5-one （Edr） on hepatic ischemia-reper- fusion （I/R） injury and liver regeneration in a porcine hepatectomy model. METHODS： One hour ischemia was...AIM： TO investigate the effect of E3-methyl-l-phe- nyl-2-pyrazolin-5-one （Edr） on hepatic ischemia-reper- fusion （I/R） injury and liver regeneration in a porcine hepatectomy model. METHODS： One hour ischemia was induced by occlud- ing the vessels and the bile duct of the right and median lobes. A 40% left hepatectomy was performed after re- perfusion. Six animals received Edr （3 mg/kg per hour） intravenously and six control animals received saline just before reperfusion. Remnant liver volume, hemody- namics, aspartate aminotransferase （AST）, alanine ami- notransferase, lactate dehydrogenase and lactic acid, were compared between the groups. The expression of transforming growth factor-β （TGF-β1） and toll-like receptor （TRL） mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction. Apoptosis was demonstrated by terminal deoxynucleo- tidyl transferase dUTP nick end labeling （TUNEL） stain- ing, respectively. RESULTS： Serum AS-I- （P = 0.029）, and toll like recep- tor 4 level （P = 0.043） were significantly lower after 3 hin animals receiving Edr. In addition, TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs. After 1 mo, all factors were non-significantly different between the two groups. CONCLUSION： Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.展开更多
A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial isc...A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.展开更多
Objective To explore the anti-inflammatory effects of magnoliae fargesii volatile oil.Methods Human umbilical vein endothelial cells (HUVECs) were stimulated by TNF-α to express the adhesion molecules. Then the anti-...Objective To explore the anti-inflammatory effects of magnoliae fargesii volatile oil.Methods Human umbilical vein endothelial cells (HUVECs) were stimulated by TNF-α to express the adhesion molecules. Then the anti-adhesion effects of magnoliae fargesii volatile oil between HUVECs and human peripheral neutrophils were observed. The ischemia-reperfusion animal models were established by 60min renal ischemia followed by 1, 3, 6 and 24h reperfusion. Rats were randomly divided into the following groups: the sham-operation controls, ischemic group only treated with normal saline, and treated group infused magnoliae fargesii volatile oil before reperfusion. Then the renal injury of rats was detected. Results High rate of cell adhesion between HUVECs and neutrophils was observed. Magnoliae fargesii volatile oil could inhibit the adhesion process at the concentration of 0.5μL/mL (191.6±8.6), 1.0μL/mL (158.2±9.0) and 2.0μL/mL (155.2±9.7) (P<0.05). The anti-adhesion effects were strengthened with the increase of volatile oil concentration. Blood urea nitrogen and creatinine levels of the animal models were significantly increased after 24h reperfusion while the increase was remarkably attenuated by the treatment with magnoliae fargesii volatile oil. The renal injury was severe after 1h reperfusion, which was significantly attenuated by the treatment of magnoliae fargesii volatile oil. Conclusion Magnoliae fargesii volatile oil has anti-inflammatory effects.展开更多
Objective: To study the change and role of heme oxygenase-1 (HO-1) in injured lungs following limb ischemia/reperfusion in rats. Methods: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used i...Objective: To study the change and role of heme oxygenase-1 (HO-1) in injured lungs following limb ischemia/reperfusion in rats. Methods: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study. Hind limb ischemia was made on 40 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, then limb reperfusion for 0, 4, 8, 16 and 24 hours (n=8 in each time point) was performed, respectively. Other 8 rats undergoing full surgical operation including isolation of the infrarenal aorta without occlusion were taken as the sham operation group. Lung tissues were obtained from the 48 animals and Northern blotting and Western blotting were employed to measure the changes of HO-1 mRNA and protein expression, respectively. Immunohistochemistry technique was used to determine the cell types responsible for HO-1 expression after limb ischemia/reperfusion. Then hind limb ischemia was made on other 12 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, among whom, 6 rats were given zinc protoporphyrin (ZnPP), an inhibitor of HO. Then limb reperfusion for 16 hours was performed on all the 12 rats. And other 12 rats underwent full surgical operation including isolation of the infrarenal aorta without occlusion, among whom, 6 rats were then given ZnPP. Then lung tissues were obtained from the 24 animals and lung injury markers, lung histology, polymorphonuclear leukocyte (PMN) count and malondialdehyde (MDA) content were detected, respectively. HO activity was determined through measuring the carboxyhemoglobin (COHb) level in artery blood with a CO-oximeter after limb ischemia/reperfusion. And the animal mortality was observed on the other 24 rats. Results: Northern blotting analysis showed that HO-1 mRNA increased significantly at 4 hours after reperfusion, peaked at 16 hours, and began to decrease at 24 hours. In contrast, no positive signal was observed in the sham and simple ischemia animals. Increased HO-1 mRNA levels were accompanied by similar increases in HO-1 protein. Lung PMNs and MDA content increased significantly at 4, 8, 16 and 24 hours after reperfusion, compared with the sham controls (P< 0.001), while they decreased in rats with reperfusion for 16 hours when compared with rats with reperfusion for 4 hours (P< 0.001). Immunohistochemical studies showed that HO-1 was expressed in a variety of cell types, including the airway epithelia, alveolar macrophages and vascular smooth muscular cells. The blood COHb level and animal mortality increased significantly after limb ischemia/reperfusion compared with the sham controls (P< 0.001). ZnPP administrated to the ischemia/reperfusion animals led to a decrease in the COHb level and an increase in lung PMN number, MDA content and animal mortality (P< 0.001 compared with ischemia/reperfusion group), and the lung injury was aggravated. Conclusions: Limb ischemia/reperfusion up-regulates pulmonary HO-1 expression, which serves as a compensatory protective response to the ischemia/reperfusion-induced lung injury in rats.展开更多
OBJECTIVE： This work aims to observe the effects of electroacupuncture on brain-derived neuro- trophic factor （BDNF） mRNA expression in mouse hippocampus following cerebral ischemia-reperfu- sion injury. METHODS： ...OBJECTIVE： This work aims to observe the effects of electroacupuncture on brain-derived neuro- trophic factor （BDNF） mRNA expression in mouse hippocampus following cerebral ischemia-reperfu- sion injury. METHODS： The models of mouse cerebral isch- emia-reperfusion injury were established. A total of 96 healthy mice were randomly assigned into 4 groups, namely, the sham surgery, model, mod- el ＋ electroacupuncture, and mode ＋ hydergine groups. Mice in the model ＋ electroacupuncturegroup were treated through electroacupuncture at the Shenshu （BL 23）, Geshu （BL 17）, and Baihui （GV 20） acupoints. Mice in the model＋hydergine group were intragastrically administered with hy- dergine （0.77 mg/kg-1.day-l）. The levels of BDNF mRNA expressions in the hippocampus were ana- lyzed through a semi-quantitative reverse transcrip- tion-polymerase chain reaction assay on days 1 and 7 after the surgeries. RESULTS： BDNF mRNA expressions in the mouse hippocampus of the model group on days 1 and 7 after the surgery were higher than those of the sham surgery group （both P〈0.01）. On days 1 and 7 of the electroacupuncture treatment, BDNF mRNA expression in the mouse hippocampus of the mod- el ＋ electroacupuncture group was significantly ele- vated compared with the model group （both P〈 0.01） or the model ＋ hydergine group （both P〈 0.01）. On days 1 and 7 of the hydergine treatment, BDNF mRNA expression in the mouse hippocam- pus of the model ＋ hydergine group tended to in- crease compared with the model group; however, statistical significance was not achieved （both P〉 0.05）. CONCLUSION： Electroacupuncture treatment en- hances endogenous BDNF expression, which may improve the survival environment for intracerebral neurons and inhibit the apoptosis of hippocampal cells.展开更多
Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebr...Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebral ischemic injury. Methods: Local cerebral ischemia-reperfusion rat model was established with modified Zea-Longa thread-occlusion method, and MSCs were injected into the caudal vein, and Buyang Huanwu Tang(补阳还五汤)was administrated. Vascular endothelial growth factor (VEGF) and Ki-67 expression in the ischemic side of the brain in the cerebral ischemic-reperfusion rat were detected with immuno-histochemical staining method. Results: VEGF and Ki-67 expressions were significantly up-regulated in the MSCs group and the combination group, with significant differences as compared with the model group and the sham operation group (P<0.05), and with the most strongest effect in the combination group. Conclusion: Buyang Huanwu Tang(补阳还五汤)combined with MSCs transplantation repairs the injured blood vessels and lesion tissues possibly by up-regulation of VEGF and Ki-67 expression.展开更多
Objective: To observe the effects of electroacupuncture on hippocampal and cortical apoptosis in a mouse model of cerebral ischemia-reperfusion injury. Methods: Mouse models established by repeated cerebral ischemia-r...Objective: To observe the effects of electroacupuncture on hippocampal and cortical apoptosis in a mouse model of cerebral ischemia-reperfusion injury. Methods: Mouse models established by repeated cerebral ischemia-reperfusion, followed by electroacupuncture at Shenshu, Geshu, and Baihui points. The control group mice were intragastrically administered Hydergine. On day 1 and 7 post-treatment, hippocampal and cortical apoptosis was detected by terminal-deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL), and apoptosis images in the hippocampal CA1 zone and cortical area were analyzed. Results: In the model group, apoptotic cells were detected one day after treatment and some cellular fibers were disarrayed. By day 7 post-treatment, there was an increase in the number of apoptotic cells in the hippocampal CA1 region. In addition, there were apoptotic cells in the cortical area, the cortical layers were thinner with localized neuronal loss and sieve-like lymphocyte infiltration, as well as glial cell proliferation and visible infarct lesions. However, in the Hydergine and electroacupuncture groups, there was a small number of apoptotic cells. At 7 days post-treatment in the model group, field number, numerical density on area, and surface density were increased. However, in the Hydergine and electroacupuncture groups these parameters were decreased (P<0.01), with a significant difference between the two treatment groups (P<0.01). Conclusion: Electroacupuncture treatment inhibited apoptosis and provided neuroprotection.展开更多
文摘AIM： TO investigate the effect of E3-methyl-l-phe- nyl-2-pyrazolin-5-one （Edr） on hepatic ischemia-reper- fusion （I/R） injury and liver regeneration in a porcine hepatectomy model. METHODS： One hour ischemia was induced by occlud- ing the vessels and the bile duct of the right and median lobes. A 40% left hepatectomy was performed after re- perfusion. Six animals received Edr （3 mg/kg per hour） intravenously and six control animals received saline just before reperfusion. Remnant liver volume, hemody- namics, aspartate aminotransferase （AST）, alanine ami- notransferase, lactate dehydrogenase and lactic acid, were compared between the groups. The expression of transforming growth factor-β （TGF-β1） and toll-like receptor （TRL） mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction. Apoptosis was demonstrated by terminal deoxynucleo- tidyl transferase dUTP nick end labeling （TUNEL） stain- ing, respectively. RESULTS： Serum AS-I- （P = 0.029）, and toll like recep- tor 4 level （P = 0.043） were significantly lower after 3 hin animals receiving Edr. In addition, TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs. After 1 mo, all factors were non-significantly different between the two groups. CONCLUSION： Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.
文摘A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.
文摘Objective To explore the anti-inflammatory effects of magnoliae fargesii volatile oil.Methods Human umbilical vein endothelial cells (HUVECs) were stimulated by TNF-α to express the adhesion molecules. Then the anti-adhesion effects of magnoliae fargesii volatile oil between HUVECs and human peripheral neutrophils were observed. The ischemia-reperfusion animal models were established by 60min renal ischemia followed by 1, 3, 6 and 24h reperfusion. Rats were randomly divided into the following groups: the sham-operation controls, ischemic group only treated with normal saline, and treated group infused magnoliae fargesii volatile oil before reperfusion. Then the renal injury of rats was detected. Results High rate of cell adhesion between HUVECs and neutrophils was observed. Magnoliae fargesii volatile oil could inhibit the adhesion process at the concentration of 0.5μL/mL (191.6±8.6), 1.0μL/mL (158.2±9.0) and 2.0μL/mL (155.2±9.7) (P<0.05). The anti-adhesion effects were strengthened with the increase of volatile oil concentration. Blood urea nitrogen and creatinine levels of the animal models were significantly increased after 24h reperfusion while the increase was remarkably attenuated by the treatment with magnoliae fargesii volatile oil. The renal injury was severe after 1h reperfusion, which was significantly attenuated by the treatment of magnoliae fargesii volatile oil. Conclusion Magnoliae fargesii volatile oil has anti-inflammatory effects.
基金ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina (No .30 2 71337)
文摘Objective: To study the change and role of heme oxygenase-1 (HO-1) in injured lungs following limb ischemia/reperfusion in rats. Methods: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study. Hind limb ischemia was made on 40 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, then limb reperfusion for 0, 4, 8, 16 and 24 hours (n=8 in each time point) was performed, respectively. Other 8 rats undergoing full surgical operation including isolation of the infrarenal aorta without occlusion were taken as the sham operation group. Lung tissues were obtained from the 48 animals and Northern blotting and Western blotting were employed to measure the changes of HO-1 mRNA and protein expression, respectively. Immunohistochemistry technique was used to determine the cell types responsible for HO-1 expression after limb ischemia/reperfusion. Then hind limb ischemia was made on other 12 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, among whom, 6 rats were given zinc protoporphyrin (ZnPP), an inhibitor of HO. Then limb reperfusion for 16 hours was performed on all the 12 rats. And other 12 rats underwent full surgical operation including isolation of the infrarenal aorta without occlusion, among whom, 6 rats were then given ZnPP. Then lung tissues were obtained from the 24 animals and lung injury markers, lung histology, polymorphonuclear leukocyte (PMN) count and malondialdehyde (MDA) content were detected, respectively. HO activity was determined through measuring the carboxyhemoglobin (COHb) level in artery blood with a CO-oximeter after limb ischemia/reperfusion. And the animal mortality was observed on the other 24 rats. Results: Northern blotting analysis showed that HO-1 mRNA increased significantly at 4 hours after reperfusion, peaked at 16 hours, and began to decrease at 24 hours. In contrast, no positive signal was observed in the sham and simple ischemia animals. Increased HO-1 mRNA levels were accompanied by similar increases in HO-1 protein. Lung PMNs and MDA content increased significantly at 4, 8, 16 and 24 hours after reperfusion, compared with the sham controls (P< 0.001), while they decreased in rats with reperfusion for 16 hours when compared with rats with reperfusion for 4 hours (P< 0.001). Immunohistochemical studies showed that HO-1 was expressed in a variety of cell types, including the airway epithelia, alveolar macrophages and vascular smooth muscular cells. The blood COHb level and animal mortality increased significantly after limb ischemia/reperfusion compared with the sham controls (P< 0.001). ZnPP administrated to the ischemia/reperfusion animals led to a decrease in the COHb level and an increase in lung PMN number, MDA content and animal mortality (P< 0.001 compared with ischemia/reperfusion group), and the lung injury was aggravated. Conclusions: Limb ischemia/reperfusion up-regulates pulmonary HO-1 expression, which serves as a compensatory protective response to the ischemia/reperfusion-induced lung injury in rats.
基金Supported by Department of Science & Technology of He-bei Province (No. 06276102D-31)Department of Health of Hebei Province (No. 2005156)Training Program for Backbone of Scientific Research Talents of Hebei Medical University (2007)
文摘OBJECTIVE： This work aims to observe the effects of electroacupuncture on brain-derived neuro- trophic factor （BDNF） mRNA expression in mouse hippocampus following cerebral ischemia-reperfu- sion injury. METHODS： The models of mouse cerebral isch- emia-reperfusion injury were established. A total of 96 healthy mice were randomly assigned into 4 groups, namely, the sham surgery, model, mod- el ＋ electroacupuncture, and mode ＋ hydergine groups. Mice in the model ＋ electroacupuncturegroup were treated through electroacupuncture at the Shenshu （BL 23）, Geshu （BL 17）, and Baihui （GV 20） acupoints. Mice in the model＋hydergine group were intragastrically administered with hy- dergine （0.77 mg/kg-1.day-l）. The levels of BDNF mRNA expressions in the hippocampus were ana- lyzed through a semi-quantitative reverse transcrip- tion-polymerase chain reaction assay on days 1 and 7 after the surgeries. RESULTS： BDNF mRNA expressions in the mouse hippocampus of the model group on days 1 and 7 after the surgery were higher than those of the sham surgery group （both P〈0.01）. On days 1 and 7 of the electroacupuncture treatment, BDNF mRNA expression in the mouse hippocampus of the mod- el ＋ electroacupuncture group was significantly ele- vated compared with the model group （both P〈 0.01） or the model ＋ hydergine group （both P〈 0.01）. On days 1 and 7 of the hydergine treatment, BDNF mRNA expression in the mouse hippocam- pus of the model ＋ hydergine group tended to in- crease compared with the model group; however, statistical significance was not achieved （both P〉 0.05）. CONCLUSION： Electroacupuncture treatment en- hances endogenous BDNF expression, which may improve the survival environment for intracerebral neurons and inhibit the apoptosis of hippocampal cells.
基金supported by Henan Province Higher Learning Institution Outstanding Scientific Research Talent Innovation Engineering Project (2007KYCX007)Henan Province Outstanding Youth Project (08100510015)
文摘Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebral ischemic injury. Methods: Local cerebral ischemia-reperfusion rat model was established with modified Zea-Longa thread-occlusion method, and MSCs were injected into the caudal vein, and Buyang Huanwu Tang(补阳还五汤)was administrated. Vascular endothelial growth factor (VEGF) and Ki-67 expression in the ischemic side of the brain in the cerebral ischemic-reperfusion rat were detected with immuno-histochemical staining method. Results: VEGF and Ki-67 expressions were significantly up-regulated in the MSCs group and the combination group, with significant differences as compared with the model group and the sham operation group (P<0.05), and with the most strongest effect in the combination group. Conclusion: Buyang Huanwu Tang(补阳还五汤)combined with MSCs transplantation repairs the injured blood vessels and lesion tissues possibly by up-regulation of VEGF and Ki-67 expression.
基金supported by Department of Science & Technology of Hebei Province (No.06276102D-31)Department of Health of Hebei Province (No.2005156)Training Program for Backbone of Scientific Research Talents of Hebei Medical University (2007)
文摘Objective: To observe the effects of electroacupuncture on hippocampal and cortical apoptosis in a mouse model of cerebral ischemia-reperfusion injury. Methods: Mouse models established by repeated cerebral ischemia-reperfusion, followed by electroacupuncture at Shenshu, Geshu, and Baihui points. The control group mice were intragastrically administered Hydergine. On day 1 and 7 post-treatment, hippocampal and cortical apoptosis was detected by terminal-deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL), and apoptosis images in the hippocampal CA1 zone and cortical area were analyzed. Results: In the model group, apoptotic cells were detected one day after treatment and some cellular fibers were disarrayed. By day 7 post-treatment, there was an increase in the number of apoptotic cells in the hippocampal CA1 region. In addition, there were apoptotic cells in the cortical area, the cortical layers were thinner with localized neuronal loss and sieve-like lymphocyte infiltration, as well as glial cell proliferation and visible infarct lesions. However, in the Hydergine and electroacupuncture groups, there was a small number of apoptotic cells. At 7 days post-treatment in the model group, field number, numerical density on area, and surface density were increased. However, in the Hydergine and electroacupuncture groups these parameters were decreased (P<0.01), with a significant difference between the two treatment groups (P<0.01). Conclusion: Electroacupuncture treatment inhibited apoptosis and provided neuroprotection.
