BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary ...BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.展开更多
BACKGROUND: Brain-dead donors are the main sources for organ transplantation, but many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liv...BACKGROUND: Brain-dead donors are the main sources for organ transplantation, but many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in BA-Ma mini pigs and the protective effects of breviscapine on hepatic function and on PKC-alpha mRNA and its protein expression. METHODS: Fifteen BA-Ma mini pigs were equally divided into 3 groups at random: brain-dead (group B), breviscapine pretreated (group P), and control (group Q. The brain-dead model was established by increasing intracranial pressure in a modified, slow and intermittent way. At 3, 6, 12, 18 and 24 hours after the initial brain-death, the levels of serum AST, ALT, TNF-alpha, IL-1 beta, and IL-6 were determined. The changes in hepatic tissues were assessed, and the expression of PKC-alpha and PKC-alpha mRNA was detected by immunohistochemistry and RTPCR, respectively. RESULTS: The levels of AST and ALT in groups B and P began to increase 12 hours after brain-death, while the values in group P were lower than those in group B (P<0.05). The levels of IL-1 beta, IL-6, and TNF-alpha in groups B and P at 3, 6, 12 and 18 hours were lower than those in group B (P<0.05). At 6, 12 and 24 hours, the expressions of PKC-a mRNA and PKC-a protein in group P were lower than those in group B (P<0.05). The degree of injury to hepatic cells in group P was milder than that in group B. CONCLUSIONS: Breviscapine inhibits the degree of PKC-alpha mRNA transcription and its protein translation, decreases the release of inflammatory factors, and thus alleviates hepatic injury during brain-death.展开更多
基金a grant from the Science & Technology Development Foundation of Guangdong Health Bureau(No.2006345).
文摘BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.
基金This study was supported by a grant from the Distinguished Innovation of Henan Province (0421002500).
文摘BACKGROUND: Brain-dead donors are the main sources for organ transplantation, but many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in BA-Ma mini pigs and the protective effects of breviscapine on hepatic function and on PKC-alpha mRNA and its protein expression. METHODS: Fifteen BA-Ma mini pigs were equally divided into 3 groups at random: brain-dead (group B), breviscapine pretreated (group P), and control (group Q. The brain-dead model was established by increasing intracranial pressure in a modified, slow and intermittent way. At 3, 6, 12, 18 and 24 hours after the initial brain-death, the levels of serum AST, ALT, TNF-alpha, IL-1 beta, and IL-6 were determined. The changes in hepatic tissues were assessed, and the expression of PKC-alpha and PKC-alpha mRNA was detected by immunohistochemistry and RTPCR, respectively. RESULTS: The levels of AST and ALT in groups B and P began to increase 12 hours after brain-death, while the values in group P were lower than those in group B (P<0.05). The levels of IL-1 beta, IL-6, and TNF-alpha in groups B and P at 3, 6, 12 and 18 hours were lower than those in group B (P<0.05). At 6, 12 and 24 hours, the expressions of PKC-a mRNA and PKC-a protein in group P were lower than those in group B (P<0.05). The degree of injury to hepatic cells in group P was milder than that in group B. CONCLUSIONS: Breviscapine inhibits the degree of PKC-alpha mRNA transcription and its protein translation, decreases the release of inflammatory factors, and thus alleviates hepatic injury during brain-death.
