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 investigate the effect of N-acetylcysteine (NAC) on the apoptosis during myocardial ischemia reperfusion injury in rats’ heart transplantation, and to explore the possible role of NAC in myocardial apoptosis.
Methods
Sixty healthy male Lewis rats (weighing, 200-220 g) were randomly divided into 3 groups, 20 rats each group (10 donors and 10 recipients). In control group, 1 mL normal saline was infused via inferior vena cava at 30 minutes before donor harvesting; in donor preconditioning group, NAC (300 mg/kg) was infused via inferior vena cava at 30 minutes before donor harvesting, but no treatment in recipients; and in recipient preconditioning group, NAC (300 mg/kg) was infused via inferior vena cava at 30 minutes before recipient transplantation, but no treatment in donors. Heart transplantation was established in each group. Blood was drawn at 6 and 24 hours after reperfusion for analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) as markers of graft injury; myocardial tissue was harvested to determine the superoxide dismutase (SOD) and lipid hydroperoxide (LPO) activity at 24 hours after reperfusion and to observe the histology and ultrastructural changes. Graft active Caspase-3 protein expression was measured by immunohistochemistry staining, and apoptosis index (AI) was calculated by TUNEL.
Results
The heart transplantation operation was successfully completed in all groups, and the rats survived to the end of the experiment. The serum levels of AST, ALT, and LDH in donor and recipient preconditioning groups were significantly lower than those in control group at 6 hours after reperfusion (P lt; 0.05); the levels of AST and ALT in donor preconditioning group and the levels of AST and LDH in recipient preconditioning group were significantly lower than those in control group at 24 hours (P lt; 0.05); and no significant difference was found between donor and recipient perconditioning groups (P gt; 0.05). The levels of AST, ALT, and LDH at 24 hours were significantly lower than those at 6 hours in each group (P lt; 0.05) except the level of ALT in recipient preconditioning group (P gt; 0.05). SOD activity and SOD/LPO in donor and recipient preconditioning groups were significantly higher than those in control group (P lt; 0.05), but no significant difference between donor and recipient preconditioning groups (P gt; 0.05); there was no significant difference in LPO activity among 3 groups (P gt; 0.05). Histological staining and transmission electron microscope showed that myocardial injury in recipient preconditioning group was obviously lighter than that in donor preconditioning group and control group. Active Caspase-3 in recipient pretreatment group was significantly higher than that in donor preconditioning group and control group (P lt; 0.05). AI of donor and recipient preconditioning groups was significantly lower than that of control group (P lt; 0.05), but no significant difference was found between donor and recipient preconditioning groups (P gt; 0.05).
Conclusion
NAC can relieve ischemia reperfusion injury in rats’ heart transplantation by improving myocardial SOD content, and reducing active Caspase-3 activity and AI, which has a protective effect on myocardial cell of donor heart.
ObjectiveTo explore the effect of hypertonic saline (HTS) pretreatment on levels of nitric oxide (NO) and endothelin-1(ET-1) and their correlation in hepatic ischemia reperfusion (HIR) injury in rats.
MethodsThe HIR injury models were made by using Pringle, s maneuver in 45 healthy adult male Sprague-Dawley rats, which were randomly divided into three groups (n=15):sham operation (SO) group, HIR group, and HTS group. The animals were killed at 1, 6, and 24 h after reperfusion. The levels of serum NO and ET-1 were measured respectively, the correlation between NO level and ET-1 level at 6 h after reperfusion was analyzed.
ResultsAt the time points of 1 h, 6 h, and 24 h after reperfusion, the serum NO levels in the HTS group and HIR group were all significantly lower than those in the SO group (P < 0.01), but the serum ET-1 levels were all significantly higher than those in the so group (P < 0.01). The serum NO levels at the time points of 1 h, 6 h, and 24 h in the HTS group were significantly higher than those at the same time in the HIR group (P < 0.01), but the serum ET-1 levels in the HTS group were significantly lower than those in the HIR group (P < 0.01). At all the time points, every detected goal had more marked level at the time point of 6 h after reperfusion. The NO level was negatively correlated with the ET-1 level.
ConclusionsHTS could change levels of serum NO and ET-1 after HIR injury, and which has a negative correlation. Its mechanism might probably stimulate serum NO level and reduce the ET-1 level through some way so as to enable both dynamic balance to the benign development direction and achieve a protective effect.
Objective To investigate the maximum tolerance limit of rats to hepatic inflow occlusion with portal vein blood bypss (PBB) in normothermia. Methods First. A new animal model was established, the animal survival rate were calculated following 7 days of reperfusion after hepatic inflow occlusion of 30, 60, 90, 100, 110, 120 min or portal triad clamping (PTC) of 30 min. And then, the hepatic energy metabolism (RCR, P/O, ATP, AKBR) was studied following 30, 90, 120 min of ischemia or 1, 6, and 24 hours of reperfusion after the ischemia. According to the reversibility of the hepatic motochondrial function injury and maximum as long as a period of liver warm ischemia of all animal postoperative 7 days survial, the safe limit of rat to hepatic inflow occlusion was evaluated. Results The survival rate on postoperative 7 days was one hundred percent subjected to 30, 60 and 90 min of hepatic inflow occlusion, and 50, 30, 20 percent in 100, 110, 120 min, respectively, the survival rate in rats with 30 min of portal triad champing was about 40 percent. The parameters of hepatic motochondrial function reflecting the degree of liver damage to ischemia showed significantly different as compared to sham group. The functional lesion was exacerbated during inital reperfusion, then was restored progressively in PBB-30 min and PBB-90 min groups, but was maintained low level in PBB-120 min and PTC-30 min groups.Conclusion The 90 minutes is the maximum limit of rats to hepatic inflow occlusion in normothermia.
To investigate the effect of intracellular glycogen on liver ischemia-reperfusion and its mechanism, histomorphological and enzymological changes, histic ATP contents, the activity of Ca2+-ATPase on cytoplasmic membrane and intracellular free Ca2+concentration were observed during the ischemia-reperfusion of three groups of rabbit livers with different glycogen content. We found that the more vigorous energy metabolism, the higher activity of Ca2+-ATPase, the lower concentration of intracellular free Ca2+ and the slighter injury of histic structure and function appeared in the liver with the more abundant glycogen. The results suggest that intracellular abundant glycogen may reduce liver ischemiareperfusion injury.
ObjectiveTo review the recent research progress about the pathogenesis and prevention of reactive oxygen species (ROS) in the hepatic ischemia-reperfusion injury (HIRI).
MethodsSearched the related literatures in recent years from the databases such as CNKI, PubMed and so on, summarized the recent research progress about the generation mechanism of ROS, the damage mechanism of ROS, and the prevention method of ROS.
ResultsA mass of ROS originated from polymorphonuclear leukocytes, Kupffer cells, mitochondria, and the enzymes in hepatic tissue in HIRI. It mainly destroyed sugar molecules of oligosaccharide chains on the cell membrane, unsaturated fatty acid, protein molecules, mitochondrial, and genetic material. This mechanism lead to cell injuried or even death. The main method of prevention and cure to HIRI is eliminating ROS by using enzymes, vitamins, Chinese herbal medicines etc.
ConclusionsThe research about ROS in HIRI has advanced. Aiming at the damage resulted from ROS in the liver, Scholars have came up with a variety of control methods which is feasible. However, many issues need to be further investigated.
【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.
From aortic declamping to weaning from cardiopulmonary bypass (CPB), myocardium needs recovery not only from surgical and ischemia/reperfusion injury, but also of its full performance of pumping function as quickly as possible. In the early period of resuming myocardial perfusion, coronary blood flow should be increased, but ventricular volume overload, large dosage of adrenaline and isoprenaline, and high-energy defibrillation should be avoided. Thenappropriate management according to cardiac function and ECG changes is needed for successful weaning from CPB.
To elucidate the mechanism of renal injury following intestinal ischemia/reperfusion, reactive oxygen metabolites in kidney and plasma were examined in 20 rats following intestinal ischemia/reperfusion by measurement of lipid proxidation (LP).The plasma lipid peroxide concentration after reperfusion was higher than that of the contol group (Ｐ＜0.01),the LP in kidney homogenate was also significantly higher (Ｐ＜0.01) following intestinal ischemia/reperfusion.Our study suggests that reactive oxygen metabolites after intestinal ischemia/reperfusion plays an important role in kidney injury.
【Abstract】 Objective To study the effects of ischemic preconditioning (IP) on the activity of nuclear factor-κB （NF-κB） and the expressions of TNF-α and intercellular adhesion molecule-1 (ICAM-1) during early reperfusion following liver transplantation in rats. Methods The models of rat orthotopic liver transplantation were established. The donor livers were stored for 2 hours in Ringers solution at 4 ℃ before transplantation. All rats were randomly divided into sham operation group （SO group）， control group and IP group. IP group was achieved by clamping the portal vein and hepatic artery of donor liver for 10 minutes followed by reperfusion for 10 minutes before harvesting. The activity of NF-κB and expressions of TNF-α and ICAM-1 at 1 h, 2 h, 4 h and 6 h after reperfusion were measured. Serum ALT, LDH were also determined. Results The liver function of recipients with IP were significantly improved. Compared with SO group， the graft NF-κB activity increased after transplantation in control group and IP group (P＜0.05), while compared with control group that was significantly attenuated at 1 h and 2 h in IP group. Similarly, hepatic levels of TNF-α and ICAM-1 were significantly elevated in control group and were reduced in IP group. Conclusion IP might down-regulated TNF-α and ICAM-1 expression in the grafts after orthotopic liver transplantation through depressed NF-κB activation， and attenuate neutrophil infiltration in the grafts after reperfusion.
