AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank...AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank,sham,I/R,and ischemia/reperfusion and drainage(I/R + D) groups(n = 8).All rats were subjected to 60 min ischemia by clamping the superior mesenteric artery,followed by 120 min reperfusion.The rats in the I/R + D group received intestinal lymph drainage for 180 min.In the sham group,the abdominal cavity was opened for 180 min,but the rats received no treatment.The blank group served as a normal and untreated control.A chromogenic limulus assay kit was used for quantita-tive detection of serum endotoxin.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,soluble cell adhesion molecules(sICAM-1),and high mobility group protein box 1(HMGB1) were determined with an enzyme-linked immunosorbent assay kit.Histological evaluations of the intestine,liver,kidney,and lung were performed by hematoxylin and eosin staining and immunohistochemistry.HMGB1 protein expression was assayed by western blot analysis.RESULTS:The serum levels of endotoxin and HMGB1 in the I/R and I/R + D groups were significantly higher than those in the sham group(endotoxin,I/R and I/R + D vs sham:0.033 ± 0.004 EU/mL,0.024 ± 0.003 EU/mL vs 0.017 ± 0.009 EU/mL,respectively,P < 0.05;HMGB1,I/R and I/R + D vs sham:5.473 ± 0.963 EU/mL,4.906 ± 0.552 EU/mL vs 0.476 ± 0.406 EU/mL,respectively,P < 0.05).In addition,endotoxin and HMGB1 were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The serum inflammatory factors IL-6,IL-1β,and sICAM-1 in the I/R and I/R + D groups were significantly higher than those in the sham group(IL-6,I/R and I/R + D vs sham:41.773 ± 9.753 pg/mL,19.204 ± 4.136 pg/mL vs 11.566 ± 2.973 pg/mL,respectively,P < 0.05;IL-1β,I/R and I/R + D vs sham:144.646 ± 29.378 pg/mL,65.829 ± 10.888 pg/mL vs 38.178 ± 7.157 pg/mL,respectively,P < 0.05;sICAM-1,I/R and I/R + D vs sham:97.360 ± 12.714 ng/mL,48.401 ± 6.547 ng/mL vs 33.073 ± 5.957 ng/mL,respectively;P < 0.05).The serum TNF-α in the I/R group were significantly higher than in the sham group(45.863 ± 11.553 pg/mL vs 18.863 ± 6.679 pg/mL,respectively,P < 0.05).These factors were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The HMGB1 immunohistochemical staining results showed no staining or apparent injury in the blank group,and slight staining at the top of the microvillus was detected in the sham group.In the I/R group,both the top of villi and the basement membrane were stained for HMGB1 in most areas,and injury in the I/R + D group was less than that in the I/R group.HMGB1 expression in the liver,kidney,and lung of rats in the I/R + D group was significantly lower than the rats in the I/R group(P < 0.05).CONCLUSION:Lymph drainage could block the "gutlymph" pathway,improve intestinal barrier function,and attenuate distant organ injury incurred by intestinal I/R.展开更多
Hepatic ischemia and reperfusion (I/R) injury during liver surgery is still the main cause of postoperative liver failure and the subsequent rise of mortality in these patients. During the last few years, a multitude ...Hepatic ischemia and reperfusion (I/R) injury during liver surgery is still the main cause of postoperative liver failure and the subsequent rise of mortality in these patients. During the last few years, a multitude of underlying mechanisms have been extensively characterized and many different protective approaches have been evaluated under experimental conditions. Some of them have already found their way into small sized clinical trials. In this Topic Highlight series of articles, we present recent insights into promising protective concepts including the regulation and optimization of hepatic blood flow, molecular mechanisms of preconditioning and pharmacological approaches with the aim of limiting hepatic I/R injury. Leading international experts present the latest experimental evidence in their fields stressing clinically relevant ideas, which are now on the edge of entering clinical practice.展开更多
The last two decades of the twentieth century have witnessed increasingly successful rates of liver transplantation. The number of liver transplantations has increased steadily while the number of organ donors has rem...The last two decades of the twentieth century have witnessed increasingly successful rates of liver transplantation. The number of liver transplantations has increased steadily while the number of organ donors has remained relatively constant. Thus a great disparity has developed between the demand and supply of donor organs and remains a major limiting factor for further expansion of liver transplantation. Although many procedures, such as split liver[1] , living-related transplantation[2] , and xenotransplantation[3], have been attempted clinically to overcome the shortage, it is hoped that livers harvested from non-heart-beating donors (NHBDs) would alleviatethe problem of organ shortage, which again becomes the focus of attention[4-9]. However, sensitivity of the liver to warm ischemia remains a major worry for use of theNHBDs. The aim of this animal study was to assess if murine liver could tolerate prolonged period of warm ischemia and to determine the optimum timing of intervention in the cadaver donor in order to preserve liver viability.展开更多
All allografts suffer a number of unavoidable ischemic insults. These, starting with brain death and ending with reperfusion, are very troublesome, as ischemia-reperfusion injury (IRI) is demonstrated to be a major ca...All allografts suffer a number of unavoidable ischemic insults. These, starting with brain death and ending with reperfusion, are very troublesome, as ischemia-reperfusion injury (IRI) is demonstrated to be a major cause of allograft damage in various types of transplantations. To counter the threat this poses to allograft function, investigators have worked diligently over the past decades in clinical settings and in the laboratory to understand the pathophysiology and immune mechanism underlying IRI hoping to ultimately devise strategies that lessen its detrimental effects on allografts. Herein, we review the major immune components of the IRI dynamic process. Better understanding of the cellular pathophysiological processes underlying IRI will hopefully result in the design of more targeted therapies to prevent the injury, hasten repair, and minimize chronic progressive allograft damage.展开更多
目的:研究富氢University of Wisconsin器官保存液(HRUW)对大鼠离体肾脏低温保存期缺血损伤的影响。方法:24只大鼠随机分为3组:正常对照组(C组)、UW液保存组(UW组)和HRUW液保存组(HRUW组),每组8只。按大鼠肾移植供肾摘取方法取下大鼠左...目的:研究富氢University of Wisconsin器官保存液(HRUW)对大鼠离体肾脏低温保存期缺血损伤的影响。方法:24只大鼠随机分为3组:正常对照组(C组)、UW液保存组(UW组)和HRUW液保存组(HRUW组),每组8只。按大鼠肾移植供肾摘取方法取下大鼠左肾。C组:肾脏不进行保存;UW组:将肾脏于4℃UW液中保存48 h;HRUW组:将肾脏于4℃HRUW液中保存48 h。分别于保存后观察各组大鼠肾脏组织形态学变化,进行肾小管损伤评分;检测肾脏组织中丙二醛(MDA)的含量及锰超氧化物歧化酶(Mn-SOD)、Caspase-3的活性。结果:HRUW组大鼠肾脏组织病理改变较UW组明显减轻,肾小管损伤评分明显降低(P<0.05)。与UW组相比,HRUW组大鼠肾脏组织内MDA含量明显降低(P<0.01),Mn-SOD活性升高(P<0.01),Caspase-3活性明显降低(P<0.01)。结论:富氢UW液减轻大鼠肾脏低温保存期缺血损伤,其机制可能与氢气(H2)抑制低温保存肾脏氧化应激反应有关。展开更多
基金Supported by The National Natural Science Foundation of China,No. 30940069the Natural Sciences Foundation of Beijing,No. 7102127
文摘AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank,sham,I/R,and ischemia/reperfusion and drainage(I/R + D) groups(n = 8).All rats were subjected to 60 min ischemia by clamping the superior mesenteric artery,followed by 120 min reperfusion.The rats in the I/R + D group received intestinal lymph drainage for 180 min.In the sham group,the abdominal cavity was opened for 180 min,but the rats received no treatment.The blank group served as a normal and untreated control.A chromogenic limulus assay kit was used for quantita-tive detection of serum endotoxin.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,soluble cell adhesion molecules(sICAM-1),and high mobility group protein box 1(HMGB1) were determined with an enzyme-linked immunosorbent assay kit.Histological evaluations of the intestine,liver,kidney,and lung were performed by hematoxylin and eosin staining and immunohistochemistry.HMGB1 protein expression was assayed by western blot analysis.RESULTS:The serum levels of endotoxin and HMGB1 in the I/R and I/R + D groups were significantly higher than those in the sham group(endotoxin,I/R and I/R + D vs sham:0.033 ± 0.004 EU/mL,0.024 ± 0.003 EU/mL vs 0.017 ± 0.009 EU/mL,respectively,P < 0.05;HMGB1,I/R and I/R + D vs sham:5.473 ± 0.963 EU/mL,4.906 ± 0.552 EU/mL vs 0.476 ± 0.406 EU/mL,respectively,P < 0.05).In addition,endotoxin and HMGB1 were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The serum inflammatory factors IL-6,IL-1β,and sICAM-1 in the I/R and I/R + D groups were significantly higher than those in the sham group(IL-6,I/R and I/R + D vs sham:41.773 ± 9.753 pg/mL,19.204 ± 4.136 pg/mL vs 11.566 ± 2.973 pg/mL,respectively,P < 0.05;IL-1β,I/R and I/R + D vs sham:144.646 ± 29.378 pg/mL,65.829 ± 10.888 pg/mL vs 38.178 ± 7.157 pg/mL,respectively,P < 0.05;sICAM-1,I/R and I/R + D vs sham:97.360 ± 12.714 ng/mL,48.401 ± 6.547 ng/mL vs 33.073 ± 5.957 ng/mL,respectively;P < 0.05).The serum TNF-α in the I/R group were significantly higher than in the sham group(45.863 ± 11.553 pg/mL vs 18.863 ± 6.679 pg/mL,respectively,P < 0.05).These factors were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The HMGB1 immunohistochemical staining results showed no staining or apparent injury in the blank group,and slight staining at the top of the microvillus was detected in the sham group.In the I/R group,both the top of villi and the basement membrane were stained for HMGB1 in most areas,and injury in the I/R + D group was less than that in the I/R group.HMGB1 expression in the liver,kidney,and lung of rats in the I/R + D group was significantly lower than the rats in the I/R group(P < 0.05).CONCLUSION:Lymph drainage could block the "gutlymph" pathway,improve intestinal barrier function,and attenuate distant organ injury incurred by intestinal I/R.
基金Supported by The International Anesthesia Research Society
文摘Hepatic ischemia and reperfusion (I/R) injury during liver surgery is still the main cause of postoperative liver failure and the subsequent rise of mortality in these patients. During the last few years, a multitude of underlying mechanisms have been extensively characterized and many different protective approaches have been evaluated under experimental conditions. Some of them have already found their way into small sized clinical trials. In this Topic Highlight series of articles, we present recent insights into promising protective concepts including the regulation and optimization of hepatic blood flow, molecular mechanisms of preconditioning and pharmacological approaches with the aim of limiting hepatic I/R injury. Leading international experts present the latest experimental evidence in their fields stressing clinically relevant ideas, which are now on the edge of entering clinical practice.
基金Shanghai Science and Technology Development Fund,№964119027.
文摘The last two decades of the twentieth century have witnessed increasingly successful rates of liver transplantation. The number of liver transplantations has increased steadily while the number of organ donors has remained relatively constant. Thus a great disparity has developed between the demand and supply of donor organs and remains a major limiting factor for further expansion of liver transplantation. Although many procedures, such as split liver[1] , living-related transplantation[2] , and xenotransplantation[3], have been attempted clinically to overcome the shortage, it is hoped that livers harvested from non-heart-beating donors (NHBDs) would alleviatethe problem of organ shortage, which again becomes the focus of attention[4-9]. However, sensitivity of the liver to warm ischemia remains a major worry for use of theNHBDs. The aim of this animal study was to assess if murine liver could tolerate prolonged period of warm ischemia and to determine the optimum timing of intervention in the cadaver donor in order to preserve liver viability.
文摘All allografts suffer a number of unavoidable ischemic insults. These, starting with brain death and ending with reperfusion, are very troublesome, as ischemia-reperfusion injury (IRI) is demonstrated to be a major cause of allograft damage in various types of transplantations. To counter the threat this poses to allograft function, investigators have worked diligently over the past decades in clinical settings and in the laboratory to understand the pathophysiology and immune mechanism underlying IRI hoping to ultimately devise strategies that lessen its detrimental effects on allografts. Herein, we review the major immune components of the IRI dynamic process. Better understanding of the cellular pathophysiological processes underlying IRI will hopefully result in the design of more targeted therapies to prevent the injury, hasten repair, and minimize chronic progressive allograft damage.
文摘目的:研究富氢University of Wisconsin器官保存液(HRUW)对大鼠离体肾脏低温保存期缺血损伤的影响。方法:24只大鼠随机分为3组:正常对照组(C组)、UW液保存组(UW组)和HRUW液保存组(HRUW组),每组8只。按大鼠肾移植供肾摘取方法取下大鼠左肾。C组:肾脏不进行保存;UW组:将肾脏于4℃UW液中保存48 h;HRUW组:将肾脏于4℃HRUW液中保存48 h。分别于保存后观察各组大鼠肾脏组织形态学变化,进行肾小管损伤评分;检测肾脏组织中丙二醛(MDA)的含量及锰超氧化物歧化酶(Mn-SOD)、Caspase-3的活性。结果:HRUW组大鼠肾脏组织病理改变较UW组明显减轻,肾小管损伤评分明显降低(P<0.05)。与UW组相比,HRUW组大鼠肾脏组织内MDA含量明显降低(P<0.01),Mn-SOD活性升高(P<0.01),Caspase-3活性明显降低(P<0.01)。结论:富氢UW液减轻大鼠肾脏低温保存期缺血损伤,其机制可能与氢气(H2)抑制低温保存肾脏氧化应激反应有关。
