Brain Ischemia ; metabolism ; pathology ; prevention & control ; Humans ; Ischemic Preconditioning ; methods ; Myocardial Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Reperfusion Injury ; metabolism ; pathology ; prevention & control

Humans ; Ischemia ; metabolism ; pathology ; therapy ; Ischemic Postconditioning ; methods ; Myocardial Reperfusion Injury ; metabolism ; pathology ; therapy

AIMTo make approach to the relationship between the changes of free zinc and ischemic neuronal damage in hippocampus after forebrain ischemia/reperfusion.

METHODSThe models of forebrain ischemia/reperfusion were established in rats. The contents of free Zn2+ were measured by TSQ fluorescence method. The Zn2+ chelator (CaEDTA) was injected into lateral ventricles in order to evaluate the effect of free Zn2+ on ischemic neuronal damage.

RESULTS(1) Zn2+ fluorescence in the hilus of dentate gyrus, CA3 region and the stratum radiatum and stratum oriens of CA1 decreased slightly at forty-eight hours after reperfusion. From seventy-two hours to ninety-six hour after reperfusion, the decreased fluorescence gradually returned to the normal level, but some fluorescence dots were found in pyramidal neurons of CA1 and the hilus of dentate gyrus. Seven days after reperfusion, all the changes of the fluorescence almost recovered. (2) The cell membrane-impermeable Zn2+ chelator CaEDTA could reduce the intracellular concentration of free Zn2+ and reduced neuronal damage after forebrain ischemia/reperfusion.

CONCLUSION(1) The synaptic vesicle Zn2+ released and then translocated into postsynaptic neurons after forebrain ischemia/reperfusion and played a role in ischemic neuronal damage. (2) The cell membrane-impermeable chelator CaEDTA could provide neuroprotection.

Animals ; Brain Ischemia ; metabolism ; pathology ; Hippocampus ; pathology ; Male ; Neurons ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology ; Zinc ; metabolism

Ischemia and reperfusion (I/R) injury is a major cause of hepatic failure after liver surgery, but no method could monitor or predict it real-time during surgery. We measured bioelectrical impedance (BEI) and cell viability to assess the usefulness of BEI during I/R in rat liver. A 70% partial liver ischemia model was used. BEI was measured at various frequencies. Adenosine triphosphate (ATP) content, and palmitic acid oxidation rate were measured, and histological changes were observed in order to quantify liver cell viability. BEI changed significantly during ischemia at low frequency. In the ischemia group, BEI increased gradually during 60 min of ischemia and had a tendency to plateau thereafter. The ATP content decreased below 20% of the baseline level. In the I/R group, BEI recovered to near baseline level. After 24 hr of reperfusion, the ATP contents decreased to below 50% in 30, 60 and 120 min of ischemia and the palmitic acid metabolic rates decreased to 91%, 78%, and 74%, respectively, compared with normal liver. BEI may be a good tool for monitoring I/R during liver surgery. The liver is relatively tolerant to ischemia, however after reperfusion, liver cells may be damaged depending upon the duration of ischemia.
Adenosine Triphosphate/metabolism ; Animals ; *Cell Survival ; Electric Impedance ; Energy Metabolism ; Ischemia/*metabolism ; Liver/*metabolism/pathology ; Male ; Palmitates/metabolism ; Rats ; Rats, Sprague-Dawley ; *Reperfusion ; Reperfusion Injury/metabolism/pathology

Animals ; Isoflavones ; pharmacology ; Liver ; metabolism ; pathology ; Liver Diseases ; metabolism ; pathology ; Rats ; Rats, Wistar ; Reperfusion Injury ; pathology ; prevention & control ; Soybeans ; chemistry

Acute myocardial infarction is one of the major causes of mortality worldwide. Reperfusion in a timely fashion is the most effective way to limit infarct size. However, reperfusion can itself prompt further myocardial injury. This phenomenon is commonly known as myocardial ischemia-reperfusion (IR) injury. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme metabolizing acetaldehyde and toxic aldehydes. Increasing evidence has revealed a cardioprotective role of ALDH2 in myocardial IR injury. Evidence from animal studies has shown that ALDH2 diminishes acute myocardial infarct size, ameliorates cardiac dysfunction and prevents reperfusion arrhythmias. The activity of ALDH2 is severely compromised if it is encoded by the mutant ALDH2*2 gene, with an incidence of approximately 40% in Asian populations. Epidemiological surveys in the Asian population have depicted that ALDH2 polymorphism is closely associated with higher prevalence of acute myocardial infarction and coronary artery disease. Therefore, targeting ALDH2 may represent a promising avenue to protect against IR injury. This review recapitulates the underlying mechanisms involved in the protective effect of ALDH2 in cardiac IR injury. Translational potential of ALDH2 in the management of coronary heart disease is also discussed.
Aldehyde Dehydrogenase ; metabolism ; Animals ; Heart ; physiopathology ; Humans ; Mitochondria, Heart ; enzymology ; Myocardial Reperfusion Injury ; Myocardium ; pathology

AIMTo investigate the effect of ligustrazine (LGT) on expression of Fas/FasL mRNA during pulmonary ischemia/reperfusion injury (PI/RI) in the rabbits.

METHODSSingle lung ischemia/reperfusion animal model was used in this study. The rabbits were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + LGT group (I/R + LGT). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic lung injury (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/FasL mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion.

RESULTSAs compared with group I/R, Fas/FasL mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group LGT. The values of AI, W/D and IQA showed significantly lower in group I/R + LGT than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + LGT.

CONCLUSIONLigustrazine has notable protective effects on PI/RI in rabbits by inhibiting Fas/FasL mRNA express in lung tissue and decreasing apoptosis.

Animals ; Apoptosis ; Fas Ligand Protein ; metabolism ; Lung ; blood supply ; Lung Injury ; metabolism ; pathology ; Pyrazines ; pharmacology ; RNA, Messenger ; genetics ; Rabbits ; Reperfusion Injury ; metabolism ; pathology ; fas Receptor ; metabolism

Objective: To investigate the role of Maresin1 (MaR1) in hepatic ischemia-reperfusion injury (HIRI). Methods: The HIRI model was established and randomly divided into a sham operation group (Sham group), an ischemia-reperfusion group (IR group), and a MaR1 ischemia-reperfusion group (MaR1+IR group). MaR1 80ng was intravenously injected into each mouse's tail veins 0.5h before anesthesia. The left and middle hepatic lobe arteries and portal veins were opened and clamped. The blood supply was restored after 1h of ischemia. After 6h of reperfusion, the mice were sacrificed to collect blood and liver tissue samples. The Sham's group abdominal wall was only opened and closed. RAW267.4 macrophages were administered with MaR1 50ng/ml 0.5h before hypoxia, followed by hypoxia for 8h and reoxygenation for 2h, and were divided into the control group, the hypoxia-reoxygenation group (HR group), the MaR1 hypoxia-reoxygenation group (MaR1 + HR group), the Z-DEVD-FMK hypoxia-reoxygenation group (HR+Z group), the MaR1 + Z-DEVD-FMK hypoxia-reoxygenation group (MaR1 + HR + Z group), and the Con group without any treatment. Cells and the supernatant above them were collected. One-way analysis of variance was used for inter-group comparisons, and the LSD-t test was used for pairwise comparisons. Results: Compared with the Sham group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β, and IL-18 in the IR group were significantly higher (P < 0.05), with remarkable pathological changes, while the level in the MaR1 + IR group was lower than before (P < 0.05), and the pathological changes were alleviated. Compared with the Con group, the HR group had higher levels of IL-1β and IL-18 (P < 0.05), while the MaR1 + HR group had lower levels of IL-1β and IL-18 (P < 0.05). Western blot showed that the expressions of caspase-3, GSDME, and GSDME-N were significantly higher in the HR group and IR group than in the other groups; however, the expression was lower following MaR1 pretreatment. The Z-DEVD-FMK exploration mechanism was inhibited by the expression of caspase-3 in HIRI when using MaR1. Compared with the HR group, the IL-1β and IL-18 levels and the expressions of caspase-3, GSDME, and GSDME-N in the HR + Z group were decreased (P < 0.05), while the expression of nuclear factor κB was increased, but following MaR1 pretreatment, nuclear factor κB was decreased. There was no significant difference in the results between the MaR1 + H/R group and the MaR1 + H/R + Z group (P > 0.05). Conclusion: MaR1 alleviates HIRI by inhibiting NF-κB activation and caspase-3/GSDME-mediated inflammatory responses.
Mice ; Animals ; NF-kappa B/metabolism* ; Interleukin-18/metabolism* ; Caspase 3/metabolism* ; Liver/pathology* ; Signal Transduction ; Reperfusion Injury/metabolism*

OBJECTIVETo investigate the effect and mechanism of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion.

METHODSA rabbit hepatic ischemia reperfusion injury model was established by hepatic portal occlusion and in situ hypothermic irrigation for 30 min. Twenty-four New Zealand white rabbits were employed and randomly divided into 3 groups equally by different dosage of portal blood stasis removal: group A5 (5 ml blood removal), group A10 (10 ml blood removal),and group B (no blood removal). Eight rabbits were served as controls with no hepatic portal occlusion and hypothermic irrigation. After reperfusion 4 h serum endotoxin content, tumor necrosis factor-alpha (TNF-alpha), urea nitrogen (BUN), and creatinine (Cr) were examined respectively, meantime lung and kidney tissues were sampled to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), the pathology, and wet to dry weight ratio, broncho-alveolar lavage fluid protein content in lung tissues.

RESULTSRemoving portal blood stasis ameliorated lung and renal injury as shown by decreasing the level of serum endotoxin, TNF-alpha, BUN, Cr, wet to dry weight ratio, broncho-alveolar lavage fluid protein content, MDA, SOD. TNF-alpha, Cr, broncho-alveolar lavage fluid protein content in lung tissues and MDA in kidney tissue in group A5 were significantly reduced compared with those in group B (P < 0.05), while in lung tissue in group A10 were also markedly reduced (P < 0.05). The activation of SOD in group A5 were significantly increased (P < 0.05).

CONCLUSIONSRemoval of portal blood stasis before the resume of splanchnic circulation may ameliorate the lung and renal injury induced by hepatic ischemia reperfusion. The possible mechanism may be that portal blood stasis removal reduces endotoxin absorption, and further decreases production of serum TNF-alpha.

Animals ; Disease Models, Animal ; Female ; Ischemia ; metabolism ; pathology ; Kidney ; metabolism ; pathology ; Liver ; blood supply ; Lung ; metabolism ; pathology ; Male ; Portal Vein ; pathology ; Rabbits ; Random Allocation ; Reperfusion Injury ; metabolism ; pathology

BACKGROUND: Necroptosis is a new form of cell death that has been identified as a third pathway causing cell death. In this study, necrostatin-1 (Nec-1) was used to determine whether necroptosis exists in a rat ischaemia/reperfusion injury flap model. METHODS: In this study, twenty male Sprague-Dawley rats were divided randomly into two groups: a control group (CTL group) and a Nec-1 group. Each abdominal skin flap underwent 3 h of ischaemia and then reperfusion. Fifteen minutes before and after reperfusion, phosphate buffer saline (PBS) was administered intraperitoneally to the CTL group, while Nec-1 was administered intraperitoneally to the Nec-1 group. Twenty-four hours after reperfusion, the whole flap was divided equally into 54 sections. Flap blood perfusion was measured. One sample was taken randomly from each row. Morphological changes, apoptosis, receptor-interacting protein-1 (RIP-1) expression and caspase-3 activity were observed and detected. The measurements between the two groups were compared with the independent t-test, and a P value of <0.05 was considered statistically significant. RESULTS: Compared to flaps in the CTL group, flaps in the Nec-1 group showed longer survival rates, better blood perfusion and less inflammatory infiltration. The total flap area considered to have survived was 70.88 ± 10.28% in the CTL group, whereas 80.56 ± 5.40% of the area was found to be living in the Nec-1 group (Nec-1 vs. CTL, t = -2.624, P < 0.05). For some rows, there were significant differences in cell apoptosis between the two groups, the apoptosis index (AI) in rows "9 cm", "7 cm", "6 cm" and "5 cm" was significantly lower in the Nec-1 group than that in the CTL group (Nec-1 vs. CTL, P < 0.05). RIP-1 expression was much lower in the Nec-1 group than that in the CTL group in rows "5 cm" to "9 cm" (Nec-1 vs. CTL, P < 0.05). No significant differences in caspase-3 activity were found. CONCLUSION According to the results, necroptosis was present in a rat abdominal ischaemia/reperfusion injury flap model.
Animals ; Apoptosis ; physiology ; Caspase 3 ; metabolism ; Male ; Necrosis ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology