Objective To investigate whether protease inhibitor (ulinastatin, UTI) can protect liver from ischemiareperfusion injury in hepatocellular carcinoma (HCC) patients undergoing hepatectomy after hepatic inflow occlusion. Methods A prospective randomized control study was designed. Thirtyone HCC patients undergoing hepatectomy after hepatic inflow blood occlusion were randomly divided into the following two groups. UTI group (n=16)， 1×105 units of ulinastatin was given intravenously in operation, then the dosage was continuously used twice a day up to 5 days postoperatively. Control group (n=15), the patients received other liver protective drugs. Liver function, plasma C-reactive protein (CRP) and cortisol level were compared between these two groups. Results The postoperative liver function of the UTI group was significantly improved compared with the control group. For example, on the third postoperative day the aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin level in the UTI group were significantly lower than those in the control group, respectively (P＜0.05). On the first postoperative day, the plasma CRP concentration in the UTI group was significantly lower than that in the control group(P＜0.01). The plasma cortisol level in the control group markedly increased compared with the level before operation(P=0.046). However, there was no significant difference in the UTI group between before and after operation. Conclusion Ulinastatin can effectively protect liver from ischemia/reperfusion injury in HCC patients undergoing hepatectomy performed after hepatic inflow occlusion. Also, it can relieve the surgical stress for patients.
【Abstract】Objective To observe the synthesis of TLR2 protein and its mRNA expression in Kupffer cells (KCs) and sinusoidal endothelial cells(SECs).Methods Thirty-two BALB/c mice divided into two groups (operation group and false operation group) were used to prepare the model of partial hepatic ischemia/reperfusion (I/R) injury. After injury KCs and SECs were isolated with twosteps situ perfusion technique. And these cells were dyed by rat anti-mouse TLR2 IgG and anti-rat IgG2b labeled with flurescein isothiocyanate (FITC). The sysnthesis of TLR2 protein were determined by flow cytometric (FCM) analysis and real time reverse transcription polymerase chain reaction (Real-Time RT-PCR) analysis for gene expression.Results As for KCs: TLR2 expression was significant higher in operation group, compared with false operation group 〔protein expression: （9.19±1.07）% vs （1.52±0.21）%, P＜0.01; gene expression: 0.54±0.77 vs 2.62±2.19, P＜0.05〕. But there were no significant differences with expression in SECs. Conclusion Synthesis of TLR2 protein and its gene expression increased in KCs in the mouse partial hepatic ischemia-reperfusion injury.
ObjectiveTo introduce the relationship between the apoptosis hepatocyte and its genic mediation and the ischemia of portal vein. MethodsThe combination of related literatures and our research findings were made.ResultsPortal vein ischemia may induced hepatocyte apoptosis, p53 and bcl2 gene alternatively adjust hepatocyte apoptosis. Expression of p53 gene is enhanced in hepatic tissue when hepatocyte apoptosis is not obvious, but after 24-72 h of portal vein ischemia, when hepatocyte apoptosis is obvious, enhanced expression of p53 gene or reduced expression of bcl2 gene occur. There exists close relationship between portal vein ischemia and hepatocyte apoptosis. Conclusion Apoptosis hepatocyte is involved in organic atrophy after ischemia of portal vein, and p53 and bcl2 gene alternatively adjust hepatocyte apoptosis. At present, the mechanism of apoptosis of hepatocyte induced by ischemia of portal vein is not clear, which needs further study.
ObjectiveTo study the protective effects of ischemia preconditioning (IPC) on cryopreservation injury of rat liver.MethodsThe model of isolated nonrecirculated perfusion rat liver was established. The grafts were treated with IPC in different time (ischemia preconditioning time in IPC1 group was 5 min; the time in IPC2 group was 10 min; while the time in IPC3 group was 15 min). The cryopreservation injury of the grafts in each group was determined and compared. ResultsThe levels of aspartate transaminase (AST) and alanine transaminase (ALT) in the effluent solutions in IPC1 group were (40.1±6.3) U/L and （17.1±0.5） U/L respectively, and IPC2 group (53.6±3.7) U/L, （19.7±0.5） U/L, which were much lower than those of nonpreconditioning (NPC) group 〔(64.5±8.2) U/L, （23.8±3.9） U/L〕 (P＜0.05). Those in IPC1 group was much lower than those in IPC2 group and IPC3 group 〔(63.8±7.2) U/L,（22.8±2.5） U/L〕 (P＜0.05). The level of lactic acid dehydrogenase (LDH) in NPC group (104.3±20.6) U/L, IPC1 group (84.1±19.7) U/L, IPC2 group (90.5±21.1) U/L, and IPC3 group (103.1±18.5) U/L were of no significant difference (Pgt;0.05). The contents of bile product and the hepatocellular contents of ATP in IPC1 group were (53.5±10.2) μl and (6.15±0.65) μmol/g respectively, and IPC2 group (41.5±8.1) μl, (4.77±0.21) μmol/g, which were much higher than those NPC group 〔(22.8±9.7) μl, (2.62±0.34) μmol/g〕 (P＜0.05). Those in IPC1 group were much higher than those in IPC2 group and IPC3 group 〔(27.5±2.8) μl, (2.61±0.29) μmol/g〕 (P＜0.05). The contents of malondialdehyde (MDA) in liver tissue in IPC1 group was (4.36±0.26) nmol/gand IPC2 group (5.51±0.13)
Objective To evaluate the phenomena of apoptosis and its relevant mechanism during ischemia-reperfusion period. Methods The published papers to explore the apoptotic phenomena and its mechanism in organs or tissues which experienced ischemia-reperfusion injury were reviewed. Results Apoptosis was common in ischemia-reperfusioned organ or tissue. The severity of apoptosis was influenced by many factors such as ischemia, hypoxia, oxygen free radials, intracellular free calcium ion overloading, various cytokines, et al; and also was regulated by bcl-2 family, caspase family and NF-κB，et al. Conclusion Apoptosis is a common phenomenum in ischemiareperfusioned organ or tissue which is affected and regulated by various factors.
Objective To establish a new model on isolated human cadaver testes with ischemiareperfusion (I/R). MethodsThirteen isolated cadaver testes contributed by 13 persons were preserved under 0℃-4℃ hypothermia and then reperfused under 37℃. Histological and histochemical changes were observed. Results4℃ cold ischemia in 12 hours induced only trivial swelling and vascular degeneration of endothelial cells (ECs), obvious pathologic changes occurred after 24 hours, including detachment of ECs, separation between basement membrane and seminiferous epithelium, degeneration and detachment of spermatogenous cell and edema of mesenchyme. Injury was worse along with the prolongation of cold preservation time. Changes of LDH and SDH activities were found by histochemical staining. Reperfusion following 6 hours ischemia induced tissue injury and unusual enzyme activity. All changes were more obvious after reperfusion following 12,18,24 or 36 hours cold ischemia.Conclusion This new model on isolated cadaver testes with ischemiareperfusion is successful, it can substitute other solid organs of human beings for I/R injury study.
Objective To investigate the pathological characteristics of hepatic energy metabolism changes following hepatic inflow occlusion and the tolerant limit to ischemia in cholestatic rats.Methods On the day 7 after rats biliary obstruction, the survival rate, hepatic mitochondrial respiratory function, content of ATP, and the ketone body ratio in arterial blood were investigated following the different duration of hepatic ischemia and reperfusion with portal blood bypass.Results The survival rate on postoperative day 10 was 100%, 100% and 40% subjected to 30, 60 and 90min of hepatic vascular occlusion. The hepatic energy metabolic function was decreased markedly following ischemia, and was increased markedly on 24 hours following reperfusion subjected to 30, 60min of hepatic vascular occlusion, but it had less increase with 90min of hepatic vascular occlusion.Conclusion The hepatic energy metabolic function injury is reversible in cholestatic rats, and the rats can tolerate hepatic inflow occlusion within 60min, but the hepatic energy metabolic function injury is irreversible after 90min of hepatic occlusion.
【Abstract】Objective To study the protective effects of anisodamine on liver ischemia-reperfusion injury in rats. Methods One hundred and sixty male Wistar rats were randomly divided into the normal control (n=10), ischemiareperfusion (n=50), normal saline (n=50) and anisodamine (n=50, 2.0 mg/kg) groups. The animals were killed 1, 3, 6, 12, 24 hours after ischemia induced for 60 minutes and followed by reperfusion. Plasma endothelin-1 (ET-1), hyaluronic acid (HA), glutamic-pyruvic transaminase enzyme (ALT) were measured, and the hepatic histopathologic alterations were also observed. Results The plasma ET-1, HA and ALT concentrations were markedly increased after liver ischemiareperfusion.The hepatic congestion was significantly obvious. An intravenous injection of anisodamine before ischemiareperfusion could decrease the plasma HA and ALT concentrations and relieve the hepatic congestion. Conclusion Anisodamine can improve hepatic microcirculatory disturbances after reperfusion and have hepatoprotictive effects on rat liver ischemia-reperfusion injury.
Objective To make clear the effect of gastrointestinal tract ischemia on multiple organ dysfunction syndrome (MODS). Methods The literature in the recent years was reviewed.Results The low-flow states of gastrointestinal tract and decrease of gastrointestinal intramucosal pH, which occured following a variety of insults (sever trauma, hemorrhagic shock, et al), as well as overgrowth of enterobacteria, may result in a significant increase of permeability of bowel and lead to endotoxemia and bacterial translocation. Ischemia also resulted in release of TNF, IL-6 into the systemic circulation, dysfunction of gastrointestinal tract motility, and activation of neutrophile which was integral in local and distant organ damage. Conclusion These data suggest that the management of correct ischemia of gastrointestinal tract, which include fluid infusion to replacement of blood volume, early enteral nutrition, improvement of gastrointestinal movement, could contribute to improve the intestinal barrier function, and prevent the development of MODS.
Objective To study the efect of IH764-3 on ischemia-reperfusion (I/R) injury in rat liver. Methods Rats were divided into 3 groups, the control group was not subjected to ischemia and no treatment was given. I/R injury group was subjected to 40 minutes ischemia followed by reperfusion for 120 minutes. The IH7643 group (40mg/kg) was administred at ischemia and reperfusion. Results In the IH764-3 group, sereum levels of ALT, AST, AKP and γ-GT were significantly lower than those in the I/R group. Energy charge level recovery was significantly higher with IH7643 (P＜0.05), hepatic ultrastructure was better preserved with IH764-3. Conclusion IH764-3 may be useful in the treatment of hepatic ischemia reperfusion injury