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
Background Both ischemic preconditioning （IPC） and limb remote ischemic postconditioning （LRIPOC） have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfu...Background Both ischemic preconditioning （IPC） and limb remote ischemic postconditioning （LRIPOC） have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury （IRI）, but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.展开更多
Background： Ischemia preconditioning （IPC） remains the most powerful intervention of protection against myocardial ischemiaJreperfusion injury （IRI）, but diabetes can weaken or eliminate its cardioprotective effe...Background： Ischemia preconditioning （IPC） remains the most powerful intervention of protection against myocardial ischemiaJreperfusion injury （IRI）, but diabetes can weaken or eliminate its cardioprotective effect and detailed mechanisms remain unclear. In this study, we aimed to explore whether changes of autophagy in the diabetic condition are attributable to the decreased cardioprotective effect of I PC. Methods： Sixty diabetic male Sprague-Dawley rats were randomly divided into the control （C）, IRI, rapamycin （R）, wortmannin （W）, rapamycin ＋ IPC （R ＋ IPC）, and wortmannin ＋ IPC （W ＋ IPC） groups. The in vivo rat model of myocardial IRI was established by ligaturing and opening the left anterior descending coronary artery via the left thoracotomy. Durations of ischemia and reperfusion are 30 min and 120 min, respectively. Blood samples were taken at 120 min of reperfusion for measuring serum concentrations of troponin I （TnI） and creatine kinase isoenzyme MB （CK-MB） using the enzyme-linked immunosorbent assay. The infarct size was assessed by Evans blue and triphenyltetrazolium chloride staining. The expressions ofLC3-11, beclin- 1, phosphoinositide 3-kinase （PI3K）, naammalian target of rapamycin （mTOR）, and P-Akt/Akt ratio in the ischemic myocardium were assessed by Western blotting. Results： Compared to the IRI group, infarct size （56.1% ± 6.1% vs. 75.4 ± 7.1%, P 〈 0.05）, serum cTnl （0.61 ± 0.21 vs. 0.95 ±0.26 ng/ml, P 〈 0.05）, and CK-MB levels （6.70 ± 1.25 vs. 11.51 ±2.35 ng/ml, P 〈 0.05） obviously decreased in the W ＋ IPC group. Compared with the C group, myocardial expressions of LC3-11 （0.46 ± 0.04 and 0.56 ± 0.04 vs. 0.36 ± 0.04, P 〈 0.05） and beclin- 1 （0.34 ± 0.08 and 0.38 ± 0.07 vs. 0.24 ±0.03, P 〈 0.05） evidently increased, and myocardial expressions of mTOR （0.26 ± 0.08 and 0.25 ± 0.07 vs. 0.38 ± 0.06, P 〈 0.05）, PI3K （0.29 ± 0.04 and 0.30 ±0.03 vs. 0.38 ± 0.02, P 〈 0.05）, and P-Ak展开更多
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.
文摘Background Both ischemic preconditioning （IPC） and limb remote ischemic postconditioning （LRIPOC） have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury （IRI）, but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.
文摘Background： Ischemia preconditioning （IPC） remains the most powerful intervention of protection against myocardial ischemiaJreperfusion injury （IRI）, but diabetes can weaken or eliminate its cardioprotective effect and detailed mechanisms remain unclear. In this study, we aimed to explore whether changes of autophagy in the diabetic condition are attributable to the decreased cardioprotective effect of I PC. Methods： Sixty diabetic male Sprague-Dawley rats were randomly divided into the control （C）, IRI, rapamycin （R）, wortmannin （W）, rapamycin ＋ IPC （R ＋ IPC）, and wortmannin ＋ IPC （W ＋ IPC） groups. The in vivo rat model of myocardial IRI was established by ligaturing and opening the left anterior descending coronary artery via the left thoracotomy. Durations of ischemia and reperfusion are 30 min and 120 min, respectively. Blood samples were taken at 120 min of reperfusion for measuring serum concentrations of troponin I （TnI） and creatine kinase isoenzyme MB （CK-MB） using the enzyme-linked immunosorbent assay. The infarct size was assessed by Evans blue and triphenyltetrazolium chloride staining. The expressions ofLC3-11, beclin- 1, phosphoinositide 3-kinase （PI3K）, naammalian target of rapamycin （mTOR）, and P-Akt/Akt ratio in the ischemic myocardium were assessed by Western blotting. Results： Compared to the IRI group, infarct size （56.1% ± 6.1% vs. 75.4 ± 7.1%, P 〈 0.05）, serum cTnl （0.61 ± 0.21 vs. 0.95 ±0.26 ng/ml, P 〈 0.05）, and CK-MB levels （6.70 ± 1.25 vs. 11.51 ±2.35 ng/ml, P 〈 0.05） obviously decreased in the W ＋ IPC group. Compared with the C group, myocardial expressions of LC3-11 （0.46 ± 0.04 and 0.56 ± 0.04 vs. 0.36 ± 0.04, P 〈 0.05） and beclin- 1 （0.34 ± 0.08 and 0.38 ± 0.07 vs. 0.24 ±0.03, P 〈 0.05） evidently increased, and myocardial expressions of mTOR （0.26 ± 0.08 and 0.25 ± 0.07 vs. 0.38 ± 0.06, P 〈 0.05）, PI3K （0.29 ± 0.04 and 0.30 ±0.03 vs. 0.38 ± 0.02, P 〈 0.05）, and P-Ak
