The protective effect of diosmetin on liver ischemia/reperfusion in mice though anti-inflammation and antioxidation / 中国药理学通报

Aim To study the role of diosmetin ( Dio) in liver ischemia/reperfusion and its possible mecha-nism.Methods Thirty-two mice were randomly di¬vided into sham group, I/R group, low-dose Dio group and high-dose Dio group, with 8 mice in each group.The I/R group received liver I/R surgery, and the sham group performed sham surgery.The low- and high-dose Dio groups received intraperitoneal injection of 10 mg • kg ~1 and 40 mg • kg ~1 Dio at 30 min before liver I/R, respectively.Blood and liver samples were collected at 24 h after reperfusion.ELISA was used to detect the levels of interleukin ( IL)-ip, 1L-6, lactic dehydrogenase ( LDH ) and aspartate transaminase ( AST) in serum.Hie levels of malondialdehyde ( MDA ) , reactive oxygen species ( ROS) , reduced glutathione (GSH) and total bilirubin (TBIL) in liver homogenate were measured.HE staining was used to observe liver injury.Immunohistochemical staining was used to observe the expression of IL-ip in liver tis¬sues.Western blot was used to detect the expression of cleaved-c a spa se-3 , p-NF-kb p65 and p-p38 proteins in liver tissues.Results Compared with sham group, the degree of liver injury in I/R group significantly in¬creased , and the levels of 1L-1 (3, 1L-6, LDH and AST in serum, MDA, ROS and cleaved-caspase-3, p-NF- kb p65 and p-p38 proteins in liver tissues markedly in¬creased ; however, the levels of GSH and TB1L signifi¬cantly decreased, and the differences in the above in¬dexes were statistically significant.Compared with I/R group, the above indexes in low- and high-dose Dio groups were significantly improved, and the effect of high-dose group was better than that of low-dose group.Conclusions Dio pretreatment can reduce liver I/R injury, which may be related to the reduction of oxida¬tive stress and inflammation-related pathways induced by liver I/R.

The effects of silymarin plus glutathione on the prevention of liver ischemia-reperfusion injury

Abstract Liver ischemia-reperfusion (IR) injury is a major clinical trouble encountered in clinical practice. This study aimed to examine the therapeutic effects of silymarin (SM) plus glutathione (GSH) on hepatic IR injury using a rat model of liver IR. Fifty male rats were randomly divided into five groups, each consisting of 10 rats as follows: Sham, IR, SM-IR, GSH-IR and SM plus GSH-IR. All groups except sham were subjected to 30-min ischemia and 24-h reperfusion. The treated groups received 100 mg/kg of SM, GSH and a mixture of SM plus GSH, 60 min prior to the IR. After a period of 24 h, blood and liver samples were collected for biochemical and histopathological evaluations. Pretreatment with SM, GSH and SM plus GSH before hepatic IR significantly decreased IR-induced elevations of aminotransferases, and significantly reduced the histopathological damage scores of the liver in the late phase of IR injury. Moreover, SM plus GSH treatment prior to liver IR significantly suppressed inflammatory process and oxidative stress as demonstrated by attenuations in tumor necrosis factor-α, myeloperoxidase and the thiobarbituric acid-reactive substances. These findings suggest that administration of SM plus GSH prior to liver IR may protect the liver parenchyma from the effects of an IR injury

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

IRF-1'role in liver ischemia reperfusion injury in mice / 中华肝胆外科杂志

Objective To investigate the role of interferon regulatory factor-1 (IRF-1) in liver ischemia/reperfusion (IR) injury and its underlying mechanism,and identify effective managements in alleviating liver IR injury.Methods Three groups of mice models with liver IR injury were well established,including control group (S),warm liver IR injury group (IR) and recombinant IRF-1 group (IRF-1).The levels of mRNA and protein,liver function and pathological changes of liver tissue were detected in group S and group IR.Additionally,the marker of IRF-1,p-Stat1,p-P38,PARP1 and Caspase-3 were measured and PCNA expression was determined in group IR and group IRF-1 mice with 6-hour liver IR injury.Results IRF-1 mRNA and protein and the levels expression of proteins were significantly elevated with peak occurred after 6-hour IR injury,which was statistic difference compare to the group S (t2h =-3.512,t6h =-4.247,t12h =-4.088,t24h =-3.851;P ＜ 0.05).Serum ALT and AST of mice detected in group IR were higher than group S at all endpoints (tALT =4.931,4.592,4.277,4.809;tAST =4.980,4.617,4.336,4.915;P ＜ 0.05).Furthermore,pathological damage change was more distinct compared with group S.The elevated levels of IRF-1,p-Statl,p-P38,PARP1 and Caspase-3 and decreased PCNA expression were determined in mice models with recombinant IRF-1 intervention.Conclusion IRF-1 expression could be closely correlated with liver IR injury,and its underlying mechanism may be attributed to activation of JNK MAPK protein and inhibition of PCNA expression.

Ischemic preconditioning vs adenosine vs prostaglandin E1 for protection against liver ischemia/reperfusion injury

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.

Protective mechanisms of hypoxia-inducible factor 1α against liver ischemia reperfusion injury / 中华肝胆外科杂志

Hypoxia-inducible factors 1α (HIF-1α) is the key cellular oxygen-sensitive transcription factors that could activate diverse pathways in regulating cellular metabolism,angiogenesis,proliferation and migration,enabling a cell to generate adaptive responses to a low oxygen or hypoxic environment.HIF-1 α has been shown to play an important role in the pathogenesis of multiple liver diseases.This review explores the impact of HIF1α on liver ischemia-reperfusion injury and liver transplantation as well as its mechanism.

Effects of dexmedetomidine on pneumonocyte apoptosis and CCAAT/enhancer binding protein homologous protein in acute lung injury induced by ischemia/reperfusion during liver transplantation in rats / 中国中西医结合急救杂志

Objective To investigate the effects of dexmedetomidine pre-treatment on pneumonocyte apoptosis and CCAAT/enhancer binding protein homologous protein (CHOP) in acute lung injury (ALI) induced by ischemia/reperfusion (I/R) during orthotopic liver transplantation in rats.Methods Forty adult male Sprague-Dawley (SD) rats were randomly divided into four groups by random number table method: sham operation group, I/R model group, dexmedetomidine low dose group and dexmedetomidine high dose group, 10 rats per group. Hepatic artery was ligated and cut off by two cuff method, and the portal vein was completely opened after donor liver transplanted into the recipient, thus, a hepatic I/R model was established. The perihepatic ligaments of rats were just separated after laparotomy in sham operation group and no other special treatment was performed. One hour prior to I/R, dexmedetomidine at a dose of 2.5μg·kg-1·h-1 and 5.0μg·kg-1·h-1, respectively, were pumped intravenously and finished within 1 hour in the rats of low dose group and high dose group. After experiment, the lung tissue was taken, and the lung wet/dry weight (W/D) ratio was determined. Pathological changes of lung tissue were observed and alveolar damage index of quantitative assessment (IQA) was tested by light microscope, and changes of ultrastructure of lung tissue were observed by transmission electron microscope. The mRNA and protein expressions of CHOP were detected respectively by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot. The apoptosis in lung tissue was determined by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) method and apoptosis index (AI) was calculated.Results Compared to sham operation group, the lung W/D ratio (4.94±0.84 vs. 2.29±0.54), IQA [(40.52±5.15)% vs. (4.55±1.85)%] and AI [(36.57±5.85)% vs. (2.85±0.95)%] in I/R model group were significantly higher (allP < 0.01); remarkable injury of lung tissue was confirmed by light microscope and transmission electron microscope in the I/R model group. Compared to I/R model group, the W/D ratio (3.29±0.85, 2.68±0.78 vs. 4.94±0.84), IQA [(23.69±2.62)%, (15.86±3.61)% vs. (40.52±5.15)%] and AI [(25.73±3.71)%, (14.66±2.61)% vs. (36.57±5.85)%] in dexmedetomidine low and high dose groups were markedly lower (allP < 0.01); under light and transmission electron microscopes, the injury of lung tissue in these two dose groups was notably alleviated. There was a large amount of apoptotic cells of pulmonary vascular endothelium and alveolar epithelium in I/R model group, while the cell apoptosis was distinctly decreased in dexmedetomidine low and high dose groups compared to that in model group. Compared to sham operation group, the expressions of CHOP mRNA [absorbance (A) value: 0.96±0.18 vs. 0.43±0.08] and protein (gray scale: 2.79±0.74 vs. 1.02±0.27) were significantly higher in I/R model group (bothP < 0.01). Compared to I/R model group, the expressions of CHOP mRNA (A value: 0.69±0.13, 0.56±0.12 vs. 0.96±0.18) and protein (gray scale: 1.96±0.58, 1.34±0.49 vs. 2.79±0.74) were significantly lower in dexmedetomidine low and high dose groups, the decrease in dexmedetomidine high dose group being more marked (allP < 0.01).Conclusion The pretreatment of dexmedetomidine can protect lung tissue against I/R injury during liver transplantation in rats, and the mechanism may be related to the suppression of CHOP activation and alleviation of lung tissue cell apoptosis.

Preconditioning effect of isoflurane on mitochondria free calcium concentrate and mitochondria permeability transition pore after liver ischemia-reperfusion injury in rat brain / 中国比较医学杂志

Objective To investigate the protective effect and the mechanism of isoflurane preconditioning on rat brain tissue suffering from rat liver ischemia-reperfusion injury .Methods 75 SD rats were randomly divided into five groups, sham group (S group);ischemia-reperfusion group (I/R group): liver ischemia for 60 min, reperfusion for 120 min;isoflurane preconditioning group ( ISO group ): 60 min before liver I/R, ISO pretreatment for 30 min; CsA +ISO group;CsA ( MPTP specific blocker ) 50 mg/kg intravenous injection , the same as ISO group after 30 min; CsA group:CsA 50 mg/kg intravenous injection .30 min before I/R.The animals were killed 24 h after ischemia and their brain were excised for measurement of mitochondrial permeability transition pore ( MPTP) and calcium content in mitochondria .The measurement of content of S-100βprotein in serum before ischemia and 120min after reperfusion through the application of Elisa kit.Results The mitochondrial Ca2+concentration of I/R group(287.32 ±26.17)was higher than that in S group (198.54 ±21.02) and the ISO group (209.74 ±29.49) ( P <0.05), and Ca2 + concentration of CsA +ISO group (267.31 ±37.52) was higher than the ISO group (P <0.05);there was not statistical significance between I/R and CsA group(288.63 ±23.15)(P <0.05).MPTP were more opened in I/R group(△S:1.73 ±0.24)than that in S group (△S:2.36 ±0.35)and ISO group(△S:2.11 ±0.32)(P <0.05),but MPTP were more opened in CsA +ISO group than that in ISO group (P <0.05).The content of S-100βprotein in serum was significantly higher in I/R group than that in sham and ISO groups (P <0.05),and the content of S-100βprotein in serum was significantly higher in CsA +ISO group than in the ISO groups ( P <0.05 ) .Conclusion The liver ischemia-reperfusion may injury the brain of the rat and isoflurane preconditioning can protect the brain on the rat .The reduce of mitochondria calcium overload and inhibition of MPTP opening are involved in the mechanism .

Effect of hyperbaric oxygen therapy on liver function during intermittent ischemia / Efeito da oxigenoterapia hiperbárica sobre a função hepática na isquemia intermitente

PURPOSE: To analyze the effects of hyperbaric oxygen therapy on liver function in rats previously subjected to ischemia and reperfusion. METHODS: A randomly distribution of 23 Wistar rats was conducted into three groups: SHAM, animals subjected to surgical stress without restricting blood flow by clamping the hepatic pedicle, IR, rats underwent hepatic vascular occlusion intermittently for two complete cycles of 15 minutes of ischemia followed by 5 min of reperfusion, IR / HBO, rats underwent hepatic pedicle clamping and thereafter exposed to hyperbaric oxygen pressure of 2 absolute atmospheres for 60 minutes. We evaluated liver function through mitochondrial function, determined by the stages 3 and 4 of respiration, respiratory control ratio (RCR) and mitochondrial permeability transition (Swelling). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also quantified . We analyzed the results using the Mann-Whitney test and were considered significant all results with p <0.05. RESULTS: There were significant differences between the results of stage 3 in SHAM vs IR group ; of the stage 4 in the groups IR vs SHAM and SHAM vs IR /HBO; of the Respiratory Control Ratio (RCR) in the group IR vs IR / HBO ; of alanine aminotransferase in the groups IR vs SHAM , SHAM vs IR/HBO and IR vs IR / HBO; aspartate aminotransferase in the groups SHAM vs IR and SHAM vs IR / HBO. CONCLUSION: The whole analysis of the mitochondiral function indicators permits us to conclude that the hyperbaric oxygen therapy acted as a protective agent of the mitochondrial function, minimizing the ischemia-reperfusion injury of the hepatic parenchyma.

OBJETIVO: Analisar os efeitos da oxigenoterapia hiperbárica sobre a função hepática de ratos previamente submetidos à isquemia e reperfusão. MÉTODOS: Realizou-se a distribuição aleatória de 23 ratos Wistar em três grupos: SHAM, animais submetidos ao estresse cirúrgico sem restrição de fluxo sanguíneo por clampeamento do pedículo hepático; IR ratos submetidos a oclusão vascular hepática de maneira intermitente em dois ciclos completos de 15 minutos de isquemia, seguidos por 5 min de reperfusão; IR/HBO, ratos submetidos ao clampeamento do pedículo hepático e ,ulteriormente , expostos a oxigenoterapia hiperbárica a pressão de 2 atmosferas absolutas durante 60 minutos. Avaliou-se a função hepática através da função mitocondrial, determinada pelos estados 3 e 4 da respiração mitocondrial, razão de controle respiratório(RCR) e transição de permeabilidade mitocondrial (Swelling) .Quantificou-se também alanina aminotransferase e aspartato aminotransferase séricas. Analisou-se os resultados pelo teste de Mann-Whitney e foram considerados significativos os valores de p < 0,05. RESULTADOS:Houve diferença significativa nos valores do estado 3 no grupo SHAM vs IR; estado 4 nos grupos SHAM vs IR, SHAM vsIR/HBO; Razão de Controle Respiratório(RCR) no grupo IR vs IR/HBO; alanina aminotransferase nos grupos SHAM vs IR, SHAM vs IR/HBO, IR vs IR/HBO; aspartato aminotransferase nos grupos SHAM vs IR , SHAM vs IR/HBO. CONCLUSÃO: A análise dos parâmetros mitocondriais como um todo permitiu concluir que a oxigenoterapia hiperbárica atuou como agente protetor da função mitocondrial, minimizando os efeitos deletérios da lesão de isquemia e reperfusão do parênquima hepático.

Effects of atrial natriuretic peptide preconditioning on hepatic ischemia-reperfusion injury in rats / 中国现代普通外科进展

Objective:To investigate the protective effects of matrine(MT) preconditioning against hepatic ischemia-reperfusion injury in rats. Methods:Fifty male SD rats were randomly allocated into 5 groups:sham operation(SO) group,ischemia-reperfusion (NS) group and MT preconditioning groups (of 3.75,7.5,15 mg/kg). Rats of NS and MT groups were injected normal saline or MT,respectively; and 15 min later,the pedicales of the left and median liver lobes were clampped for 45 minutes,and reperfused for 40 min. The portal trial were only separated but not obstructed in SO rats. After reperfusion,the serum activity of ALT,AST and LDH was determined,the activity of SOD and content of MDA in liver tissue were examined,and histopathological changes of liver were observed. Results:Compared with those of NS group,the serum levels of ALT,AST,LDH,and the content of MDA in liver tissue of MT groups were lower,and the activity of SOD was higher(P

Protection of Intrahepatic Injection of Liposome-mediated VEGF Plasmid against Ischemia-reperfusion Liver Injury / 华中科技大学学报(医学版)

Objective To explore the effect of intrahepatic injection of liposome-mediated VEGF plasmid on ischemia-reper-fusion liver injury and its mechanism. Methods Rabbits were randomly divided into normal group, ischemia-reperfusion group and recombinant VEGF therapy group( liposome-mediated transfer of VEGF plasmid into liver via portal vein 20 min before ischemia of liver). The model of liver ischemia-reperfusion injury was established. Liver function and the activity of SOD.XO in blood were determined at the 0,2nd,6th,12th,and 24th h after operation. RT-PCR technique was applied to detect the expression level of Fas mRNA in liver tissues of every group,and flow cytometry was used to measure cell apoptosis rate at the 6th h after operation. At the 24th h after operation,all rabbits were killed and liver tissues of ischemia were taken to make pathological sections for observing the morphology and microstructure under the light microscopy and electron microscopy. ResuJts The level of ALT in recombinant VEGF therapy group was markedly reduced as compared with ischemia-reperfusion group at the 6th,12th,and 24th h after operation( P<0. 05). The activity of SOD in recombinant VEGF therapy group was significantly higher than in ischemia-reperfusion group at the 6th, 12th,and 24th h after operation. The activity of XO in recombinant VEGF therapy group was significantly lower than that in ischemia-reperfusion group at the 6th,12th,and 24th h after operation(P< 0. 05 or P<0. 01). In addition,there was significant difference in the expression of Fas mRNA and cell apoptosis rate between recombinant VEGF therapy group and ischemia-reperfusion group(P<0. 01). The injury of hepatocytes in recombinant VEGF therapy group was significantly alleviated as compared with that in ischemia-reperfusion group under the light microscopy and e-lectron microscopy. Conclusion Liposome-mediated transfer of VEGF plasmid into liver before ischemia of liver can obviously protect hepatocytes by increasing anti-oxidative ability, decreasing the expression of Fas mRNA, and finally inhibiting hepato-cyte apoptosis.

Pyruvate kinase activation and lipoperoxidation after selective hepatic ischemia in Wistar rats / Ativação da piruvato quinase e lipoperoxidação após isquemia hepática seletiva em ratos Wistar

PURPOSE: Hepatic ischemia and reperfusion can cause several problems in hepatic surgery. The aim of this study was to determine pyruvate kinase activation and lipid peroxidation after hepatic ischemia. METHODS: Twenty-four Wistar rats were submitted to 90 minutes of selective liver ischemia and 15 minutes of reperfusion. Twelve animals were submitted to selective liver ischemia and reperfusion (Group A) and the other 12 were submitted to sham operation (Group B). After 15 minutes of reperfusion, the following parameters were measured: mean arterial pressure (MAP), alanine aminotransferase (ALT), glycemia (GLY), hepatic glycogen (GH), pyruvate kinase (PK) activation, hepatic glutathione (GSH) and malondialdehyde (MDA). Analysis of the results were made by the Student t-test and has been considered significant difference for p<0.05. RESULTS: A and B were differents for all parameters analized. CONCLUSION: The animals of group A showed reperfusion syndrome with a fall in MAP, activation of glycid metabolism through the glycolitic pathway and presence of lipid peroxidation compared to group B.

OBJETIVO: A isquemia e reperfusão hepática podem causar graves repercussões hepatocelulares em cirurgias hepáticas. O objetivo deste estudo foi determinar o comportamento da piruvato EM PORTUGUES quinase e a lipoperoxidação após isquemia hepática. MÉTODOS: Foram utilizados vinte e quatro ratos Wistar machos divididos em dois grupos. Doze animais foram submetidos a 90 minutos de isquemia hepática seletiva e reperfusão hepática de por 15 minutos (pressão arterial média (PAM), alanina aminotransferase (ALT), glicemia (GLI), gicogênio hepático (GH), ativação da piruvato quinase (PQ), glutationa hepática (GSH) e malondialdeído (MDA). Os resultados foram analisados utilizando o teste t de Student sendo as diferenças consideradas significativas para p<0,05. RESULTADOS: Verificou-se diferença significativa entre os grupos em todos os parâmetros analisados. CONCLUSÃO: Verificou-se que os animais do grupo A mostraram síndrome de reperfusão com queda da PAM, ativação do metabolismo da glicose através da via glicolítica e presença de lipoperoxidação quando comparada com o grupo B.

Hepatic microcirculatory failure / Falência microcirculatória hepática

Liver ischemia has been considered a frequent problem in medical practice, and can be associated to a number of surgical and clinical situations, such as massive hepatic resections, sepsis, liver trauma, circulatory shock and liver transplantation. After restoring blood flow, the liver is further subjected to an additional injury more severe than that induced by ischemia. On account of the complexity of mechanisms related to pathophysiology of ischemia and reperfusion (I/R) injury, this review deals with I/R effects on sinusoidal microcirculation, especially when steatosis is present. Alterations in hepatic microcirculation are pointed as a main factor to explain lower tolerance of fatty liver to ischemia-reperfusion insult. The employment of therapeutic strategies that interfere directly with vasoactive mediators (nitric oxide and endothelins) acting on the sinusoidal perfusion seem to be determinant for the protection of the liver parenchyma against I/R. These approaches could be very suitable to take advantage of marginal specimens as fatty livers, in which the microcirculatory disarrangements hamper its employment in liver transplantation.

A isquemia hepática é um problema relativamente freqüente na prática clínica, sobrevindo em situações diversas como ressecções hepáticas maciças, sepse, trauma hepático extenso, choque circulatório e transplante hepático. Durante a restauração do fluxo sanguíneo, o fígado é submetido a uma agressão adicional ainda mais intensa que aquela imposta pela isquemia. Devido à complexidade dos diversos mecanismos envolvidos na fisiopatologia da lesão por isquemia e reperfusão (I/R) hepática, esta revisão se limitará a discorrer sobre os efeitos da I/R na microcirculação sinusoidal, com ênfase para as alterações microvasculares que tomam lugar no fígado esteatótico pós-isquêmico. O desarranjo microcirculatório é apontado como um importante fator para explicar a reduzida tolerância do fígado esteatótico ao insulto isquêmico. O desenvolvimento de estratégias terapêuticas capazes de interferir diretamente com os mediadores vasoativos (óxido nítrico e endotelinas) relacionados ao déficit perfusional será determinante para a proteção do parênquima hepático frente às alterações induzidas pela I/R. Esses recursos seriam de especial interesse para o aproveitamento de fígados marginais, cuja falência microcirculatória compromete sobremaneira sua utilização para o transplante hepático.

Protective effects of propofol on renal injury during liver ischemia-reperfusion / 中国康复理论与实践

@#ObjectiveTo investigate the remote renal injury after liver ischemia-reperfusion(I/R) and the renal protection afforded by propofol.Methods 72 male SD rats were randomly divided into three groups:normol control group, I/R group and propofol group .The animals were killed after 60 minutes ischemia of liver followed by reperfusion for 4 h,2 h. Blood urea nitrogen (BUN) and creatinine (Cr) were detected,and renal histopathologic lesion were observed.ResultsIn I/R group,the serum level of BUN and Cr increased significantly compared with the baseline before liver I/R,while propofol could decrease the serum level of BUN and Cr significantly.ConclusionPropofol can reduce the renal injury during liver I/R.

Protective Effect of Peroxisome Proliferator-Activated Receptor ? Activator 15-Deoxyprostaglandin J_2 in Rat Hepatic Ischemia-Reperfusion Injury and Its Mechanism / 中国普外基础与临床杂志

Objective To investigate the protective effect of peroxisome proliferator-activated receptor ?(PPAR?) activator 15-deoxyprostaglandin J2(15d-PGJ2) in rat hepatic ischemia-reperfusion injury and its mechanism.Methods The models of 70% warm ischemia-reperfusion injury were established in SD rats,rats were randomly divided into 4 groups: sham operation group,ischemia-reperfusion group,15d-PGJ2 group and 15d-PGJ2+GW9662 group.After reperfusion,serum AST and ALT levels were determined;the liver tissues were removed for measurement of activity of NF-?B and myeloperoxidase(MPO),TNF-? content and expression of ICAM-1.Results Compared with sham operation group,the serum levels of ALT and AST,and the activities of MPO and NF-?B,TNF-? content and expression of ICAM-1 in ischemia-reperfusion group,15d-PGJ2 group and 15d-PGJ2+GW9662 group were greatly improved(P

Protective effect of liver ischemic preconditioning on the extrahepatic organs injury induced by liver ischemia/repurfusion in rats / 中国普通外科杂志

Objective To study the protective effect of liver ischemic preconditioning on the extrahepatic organs injury induced by liver ischemia/repurfusion in rats. Methods Seventy-two Sprague-Dawley rats were randomly assigned into group IP,group I/R and group S (sham-operation group), each group had 24 rats. After ischemic preconditioning and ischemia/repurfusion animal models were set up,the pathological changes of small intestine, pancreas, myocardium, kidney, lung, brain and skeletal muscle tissues were observed at 2h,24h and 1week,respealively. Results (1) The degree(s) of small intestinal injury: at 2h and 24h, The injury in group IP and group I/R were significantly higher than that in group S (all P

Avaliação da função mitocondrial do fígado submetido a isquemia parcial com e sem pré-condicionamento isquêmico

The influence of a 5 minute ischeamic pré-conditioning on the effect of 2 hours of ischeamia of the liver, followed by one hour of reperfusion, was studied. The Respiratory Control Ratio (RCR) was significantly greater in the animals submitted to pre-conditioning.

Estudou-se o papel do pré-condicionamento isquêmico de 5 minutos sobre o efeito da isquemia hepática de 2 horas seguida de reperfusão de 1 hora. Verificou-se a Razão de Controle Respiratório (RCR) foi significativamente maior nos animais submetidos à isquemia hepático com pré-condicionamento prévio de 5 minutos.

Changes of Hemodynamics and Nitric Oxide during Liver Ischemia/Reperfusion of Pig / 대한마취과학회지

BACKGROUND: Surgical hepatic inflow obstructions such as the Pringle Maneuver (PM) or hepatic vascular exclusion (HVE) can reduce bleeding during hepatic resection, but ischemia/reperfusion injury of the liver and systemic hemodynamic changes are also inevitable during and after PM or HVE. Nitric oxide plays a pivotal role in ischemia/reperfusion injury. We evaluated hemodynamic changes and changes of nitric oxide during liver ischemia/reperfusion injury excluding the effects of intestinal ischemia. METHODS: Liver ischemia was induced by clamping of the portal triad, infrahepatic and suprahepatic inferior vena cava for 90 minutes. To exclude the effects of intestinal ischemia during liver ischemia, portal and iliac venous blood was bypassed to the jugular vein using a pump. Hemodynamic parameters and nitric oxide were measured serially; before and during ischemia, and after reperfusion. RESULTS: Mean arterial blood pressure (MAP) was well-maintained during ischemia, but after reperfusion, MAP, cardiac output (CO) and stroke volume (SV) significantly decreased (35 - 40, 30 - 40 and 30%, respectively) postischemia. Compared to preischemia, systemic vascular resistance and heart rate did not change after reperfusion. Pulmonary vascular resistance and mean pulmonary arterial blood pressure significantly increased (220 - 250% and 60 - 70%) after reperfusion. Nitric oxide (NO) did not change until 20 minutes after reperfusion, but after 40 minutes reperfusion, NO significantly decreased (20%) compared to preischemia. CONCLUSIONS: After 90 minutes warm liver ischemia/reperfusion causes hypotension induced by decreased CO and SV. Increased PVR seems to be the cause of decreased CO and SV. NO-SVR interaction does not seem to be the cause of postreperfusion hypotension.

Protective effect of pentoxifylline on ischemia/reperfusion injury for the liver in rats / 中国普通外科杂志

Objective To study the role of early release of tumor necrosis factor-?(TNF-?) and nuclear factor-?B(NF?B) activation on inflammatery mediators expression and neutrophil accumulation in the liver after ischemia/reperfusion . Methods The models of partial hepatic ischemia in Wistar rats were established. Rats received either Pentoxifylline (PTX) 50mg/kg(PTX group) or sterile saline (control group) via peritoneal injection at 1h before ischemia;Sham operation group was also established. Results Compared with control group,in PTX treatment group, the release of the TNF-?, the content of NF?B p65, expression of MIP-2 mRNAand ICAM-1 mRNA were significant decreased;the levels of MPO,AST,ALT, LDH,and W/D were also reduced significantly(all P

Significance of TLR2 expression in ischemic liver tissue after liver ischemia/reperfusion in mice / 中国普通外科杂志

Objective To explore Toll like receptor 2 (TLR2) expression after partial liver ischemia/ reperfusion (I/R) in BALB/c mice and its relationship with liver function impairment. Methods All the animals were randomly divided into ischemia/reperfusion injury (I/R) and sham operation (S) groups. Total RNA was extracted from the liver samples and the expression of TLR2 mRNA was analyzed quantitatively by real time PCR method. Membrane protein was extracted, and the expression of TLR2 protein was detected by western blot method. Portal vein serum and plasma were taken for further detection of the levels of alanine aminotransferase (ALT), tumor necrosis factor alpha (TNF ?) and endotoxin . Results After 1h of partial liver ischemia and 4 h of reperfusion, the expression of TLR2 mRNA and TLR2 protein were both remarkably upregulated in tissues of ischemic liver lobes in I/R group compared with that in S group (value of TLR2mRNA: 1.06?0.91vs5.08?1.32,P0.05). Conclusions TLR2mRNA and TLR2 protein expression were upregulated in tissues of ischemic liver lobes after partial I/R injury in mice, and were associated with increased levels of portal vein ALT and TNF ?,and impairment of liver function.