Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms ...Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in- duced a photochemical model of cerebral infarction in an inbred line of mice （BALB/c）. Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved neu- rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.展开更多
BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is consider...BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P < 0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P < 0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P < 0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.展开更多
A concept of tissue adaptation to hypoxia(i.e. hypoxic preconditioning) was developed and its corresponding animal models were reproduced in 1966s. The methods of model reproduction in rat,rabbit,and mouse in particul...A concept of tissue adaptation to hypoxia(i.e. hypoxic preconditioning) was developed and its corresponding animal models were reproduced in 1966s. The methods of model reproduction in rat,rabbit,and mouse in particular and the main results are brifly introduced in this review. The tolerance to hypoxia of preconditioned animals is significantly increased. Regular changes in animals’ behavior,neurophysiology,respiratory and circulatory physiology,neuromorphology in vivo and function of brain and spinal cord in vitro are briefly demonstrated.The protective effects in vivo and in vitro of homogenate extract taken from the brain of preconditioned animals,neurochemcals and molecular neurobiological alterations are briefly presented. The essence and significance of tissue adaption to hypoxia/hypoxic preconditioning are discussed in the review in terms of evolution and practical implication.展开更多
In order to investigate the protective effect of hypoxic preconditioning on the cerebral ischemia-reperfusion injury, the expression of Bcl-2 and Bax was detected by using immunohistochemical staining after 3 h cerebr...In order to investigate the protective effect of hypoxic preconditioning on the cerebral ischemia-reperfusion injury, the expression of Bcl-2 and Bax was detected by using immunohistochemical staining after 3 h cerebral ischemia followed by 1, 6, 12, 24 and 48 h reperfusion respectively in rats treated with or without hypoxic preconditioning before cerebral ischemia. In addition, the apoptosis of neural cells and the behavioral scores for neurological functions recovery were evaluated by TUNEL staining and ＂crawling method＂, respectively. Compared with control group （cerebral ischemia-reperfusion without hypoxic preconditioning）, the expression of Bcl-2 was significantly increased, but that of Bax decreased in the hypoxic preconditioning group （cerebral ischemiareperfusion with hypoxie preconditioning）, both P〈0.05. The pre-treatment with hypoxic preconditioning could reduce the apoptosis of neural cells and promote the neurological function recovery as compared to control group. It was suggested that hypoxic preconditioning may have protective effects on the cerebral ischemia-reperfusion injury by inhibiting the apoptosis of neural cells, increase the expression of Bcl-2 and decrease the expression of Bax.展开更多
Objective:To investigate the effect of ischemic precondition to protect ischemia-reperfusion injury and reduce IL-6 expression in the rats liver transplantation.Methods:The rat portal vein infusion of autologous liver...Objective:To investigate the effect of ischemic precondition to protect ischemia-reperfusion injury and reduce IL-6 expression in the rats liver transplantation.Methods:The rat portal vein infusion of autologous liver transplantation model were used.The rats were divided into ischemic preconditioning rats liver transplantation group(A group),the rats liver transplantation group(B group) and the normal rat control group(C group).Then we analyzed the changes of liver function,liver microstructure and the expression of IL-6,SOD and MDA within 48 h.Results: The pathology of liver in group A showed lobular architecture essentially normal,the liver cells was slightly swell and no significant changes in postoperative 12 h.In transmission electron microscope(46 000X).the mitochondria of liver cells in group A i】ecame swelling,elliptical can cristae partially broken.But there still has a small amount of arrangement.While that in group, the mitochondria were swollen,became round,serious visible crest reduce or ruptured.The result of over function test showed that the serum ALT and AST levels in group A and B were both higher than that in group C at each time period,but the serum ALT and AST levels in group A were lower than that in group B.The expression changes of IL-6 in group B were higher than that in group A and R(P【0.05).The expression of MDA in group A is more obvious than that in group B(P【0.05).Conclusions:Ischemic precondition could alleviate part of ischemia-reperfusion injury in the rat liver transplantation,and also could reduce IL-6 expression to protect the liver cells against liver damage and inflammatory cytokine production.展开更多
基金supported by the National Natural Science Foundation of China,No.30870854the Natural Science Foundation of Beijing,No.7111003the Natural Science Foundation of Shandong Province,No.ZR2010HM029
文摘Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in- duced a photochemical model of cerebral infarction in an inbred line of mice （BALB/c）. Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved neu- rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.
基金supported by grants from the Health Bureau(H200770)Technology Bureau(BS2005038)of Jiangsu Province,China
文摘BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P < 0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P < 0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P < 0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.
基金This work was supported by the National Natural Science Foundation of China (No. 30370569) and the Major InternationalCollaborative Program of National Natural Science Foundation of China (No. 30620130111).
文摘A concept of tissue adaptation to hypoxia(i.e. hypoxic preconditioning) was developed and its corresponding animal models were reproduced in 1966s. The methods of model reproduction in rat,rabbit,and mouse in particular and the main results are brifly introduced in this review. The tolerance to hypoxia of preconditioned animals is significantly increased. Regular changes in animals’ behavior,neurophysiology,respiratory and circulatory physiology,neuromorphology in vivo and function of brain and spinal cord in vitro are briefly demonstrated.The protective effects in vivo and in vitro of homogenate extract taken from the brain of preconditioned animals,neurochemcals and molecular neurobiological alterations are briefly presented. The essence and significance of tissue adaption to hypoxia/hypoxic preconditioning are discussed in the review in terms of evolution and practical implication.
基金This work was supported by the Excellent Young Teachers Program of Ministry of Education of Chian Scientific Developing Program of Beijing Municipal Commission of Education (200KJ080+2 种基金 KM200310025100) Beijing Natural Science Foundation (7032005) Nati
文摘In order to investigate the protective effect of hypoxic preconditioning on the cerebral ischemia-reperfusion injury, the expression of Bcl-2 and Bax was detected by using immunohistochemical staining after 3 h cerebral ischemia followed by 1, 6, 12, 24 and 48 h reperfusion respectively in rats treated with or without hypoxic preconditioning before cerebral ischemia. In addition, the apoptosis of neural cells and the behavioral scores for neurological functions recovery were evaluated by TUNEL staining and ＂crawling method＂, respectively. Compared with control group （cerebral ischemia-reperfusion without hypoxic preconditioning）, the expression of Bcl-2 was significantly increased, but that of Bax decreased in the hypoxic preconditioning group （cerebral ischemiareperfusion with hypoxie preconditioning）, both P〈0.05. The pre-treatment with hypoxic preconditioning could reduce the apoptosis of neural cells and promote the neurological function recovery as compared to control group. It was suggested that hypoxic preconditioning may have protective effects on the cerebral ischemia-reperfusion injury by inhibiting the apoptosis of neural cells, increase the expression of Bcl-2 and decrease the expression of Bax.
文摘Objective:To investigate the effect of ischemic precondition to protect ischemia-reperfusion injury and reduce IL-6 expression in the rats liver transplantation.Methods:The rat portal vein infusion of autologous liver transplantation model were used.The rats were divided into ischemic preconditioning rats liver transplantation group(A group),the rats liver transplantation group(B group) and the normal rat control group(C group).Then we analyzed the changes of liver function,liver microstructure and the expression of IL-6,SOD and MDA within 48 h.Results: The pathology of liver in group A showed lobular architecture essentially normal,the liver cells was slightly swell and no significant changes in postoperative 12 h.In transmission electron microscope(46 000X).the mitochondria of liver cells in group A i】ecame swelling,elliptical can cristae partially broken.But there still has a small amount of arrangement.While that in group, the mitochondria were swollen,became round,serious visible crest reduce or ruptured.The result of over function test showed that the serum ALT and AST levels in group A and B were both higher than that in group C at each time period,but the serum ALT and AST levels in group A were lower than that in group B.The expression changes of IL-6 in group B were higher than that in group A and R(P【0.05).The expression of MDA in group A is more obvious than that in group B(P【0.05).Conclusions:Ischemic precondition could alleviate part of ischemia-reperfusion injury in the rat liver transplantation,and also could reduce IL-6 expression to protect the liver cells against liver damage and inflammatory cytokine production.
