LIPOCALIN-2 EXPRESSION IS ASSOCIATED WITH APOPTOSIS FOLLOWING ISCHEMIA/REPERFUSION IN A SYNGENEIC CARDIAC TRANSPLANT MODEL.
Felix AignerJakob TroppmairP ObristH. G. SchwelbergerAnja TeichertGerald BrandacherAlbert AmbergerWalter MarkGeorg SchäferR. MargreiterS. Schneeberger
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P67 Aims: Ischemia and reperfusion (I/R) during heart transplantation results in inflammation and cell death. Lipocalin-2 (24p3), a member of the lipocalin protein superfamily, is a marker for acute inflammatory response and induction of apoptosis. The aim of this study was to investigate 24p3 expression in association with the presence of apoptosis in a murine cardiac transplant model. Methods: C57BL/6 hearts were heterotopically transplanted to syngeneic recipients. Grafts were transplanted immediately or underwent 10h of cold ischemia prior to transplantation. At 2min., 2h, 12h, 24h, 2 and 10 days after transplantation (n=5 per group and timepoint) graft function was assessed before organ retrieval. RT-PCR and cDNA microarrays were performed for gene expression analysis. Morphology was determined by HE histology, protein production was investigated by immunohistochemistry using a polyclonal antibody. Apoptosis was analysed using TUNEL assay. Results: 10h of cold ischemia resulted in impaired graft function immediately after reperfusion. At later timepoints, however, there was no difference anymore. HE staining demonstrated dense mononuclear infiltrates, cellular edema and small focal necrosis in groups with and without 10 hours of cold ischemia. 24p3 gene expression was first upregulated at 12h, transcription was higher in groups without cold ischemia (22/8,8-fold). At later timepoints, 24p3 was found at lower levels in both groups. Upregulation of gene transcription was reproducible by PCR. 24p3 positive cells were identified as granuolcytes and macrophages. Apoptotic cells were first detectable at 2 days, the number peaked 10 days after transplantation. Conclusions: This study demonstrates expression of 24p3 following I/R in cardiac transplantation by infiltrating leukocytes. 24p3 production is associated with apoptosis in transplanted hearts. Prolonged cold ischemia does not enhance 24p3 expression. Lipocalin-2 is potentially a novel mechanism to induce apoptosis in the chosen setting and antagonization may provide a strategy to prevent organ damage in response to ischemia and reperfusion.Neutrophil gelatinase-associated lipocalin
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Ischemia is defined as cell death caused by insufficient perfusion of the tissue due to reduction in arterial or venous blood flow, depletion of cellular energy storages, and accumulation of toxic metabolites. The positive effects of controlled reperfusion are known and are used clinically. But the positive effects of controlled reperfusion on ovarian tissue have not been seen in the literature yet. The biochemical and histopathological comparative investigation of rat ovaries that were experimentally exposed to ischemia (IG), ischemia-reperfusion (I/R), and ischemia-controlled reperfusion (ICR) was aimed. Forty rats were divided into four groups (10 rats per group). First group: 3 h ischemia by vascular clips on ovarian tissue. Second group: 3 h ischemia + 1 h reperfusion. Third group: 3 h ischemia + 1 h controlled reperfusion (on-off method: controlled reperfusion by opening and closing the clips (on/off) in 10-second intervals, for 5 times for a total of 100 seconds). Fourth group: healthy rats. Biochemical (tGSH, MDA, and DNA damage level and SOD activity) and histopathological analysis were performed. The highest glutathione and superoxide dismutase measurements were found in ischemia/controlled reperfusion group among the ischemia or ischemia/reperfusion groups. Similarly the damage indicators (malondialdehyde, DNA damage level and histopathological damage grade) were the lowest in ischemia/controlled reperfusion group. These results indicate that controlled reperfusion can be helpful in minimizing ischemia-reperfusion injury in ovarian tissue exposed to ischemia for various reasons (ovarian torsion, tumor, etc.).
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Objective: To study NF-κB and IL-6 expression in a rat retina that has been inj ured by ischemia-reperfusion and the effect of β-aescin on its expression.Methods: A retinal model of the rat retina for ischemia-reperfusion was establi s hed. 60 SD rats were divided into two groups: one was an ischemia-reperfusion g r oup and the other was an ischemia-reperfussion and β-aescin group. Each group wa s then divided into sub-groups according to the amount of time after ischemia- re perfusion:1 hour,6 hours,12 hours,24 hours,48 hours,and 72 hours. Each sub -group consisted of 5 rats. NF-κB mRNA and IL-6 mRNA in the rat retina was m easured by the ISH method. Each rat was examined by ERG before being sacrificed.Results: NF-κB and IL-6 began to express at 6 hours after ischemia-reperfusio n i n the ischemia-reperfusion group. The highest level of expression occurred 24 h o urs after injury. In the ischemia-reperfusion and β-aescin group,the NF-κB and IL-6 expressed at 12 hours after ischemia-reperfusion injury and reached the hi ghest level at 24 hours. However,its level was lower than the level for the isc hemia-reperfusion group at every stage(P0.05). The b wave of the ERG in the is chemia-reperfusion group was lower than that for the ischemia-reperfusion and β-aescin group at every stage(P0.05).Conclusion: NF-κB may induce IL-6 and play an important role in ischemia-reperfusion inj ury in the rat retina. The β-aescin may suppress NF-κB activity and protect the retina from injury caused by ischemia-reperfusion.
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[Objective]To study the IL-6 express in rat's retina which injuried by ischemia-reperfusion and the effect of β-aescin on its expression. The model of rat's retina ischemia-reperfusion was employed. 60 SD rats were devided into two groups, one was ischemia-reperfusion group, the other was ischemia-reperfusion andβ-aescin group. Every group was devided into 1 hour, 6 hour, 12 hour, 24 hour, 48 hour and 72 hour groups. Every group had 5 rats. IL-6 mRNA was measured by ISH method in rat's retina. Every rat was examinated ERG before executed. IL-6 began to express at 6 hours after ischemia-reperfusion in ischemia-reperfusion group. It expressed most at 24 hours after ischemia-reperfusion injury. In ischemia-reperfusion and β-aescin group, IL-6 expressed at 12 hours after ischmia-reperfusion injury and reached the hightest level was lower than ischemia-reperfusion group at every stage (P 0.05). The a wave of ERG of ischemia-reperfusion group was lower than ischemia-reperfusion and β-aescin group at every stage (P 0.05). [Conclusion] IL-6 take important role in rat's retina ischemia-reperfusion injury, the β-aescni may suppress the activity of IL-6 and relieve the retina injury from the ischemia-reperfusion.
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Objective To investigate the effect of palm oil(PO) on the volume of the infarction,the expression of Bcl-2 and Bax protein following focal cerebral ischemia/reperfusion in rats,and explore the protective effect of PO on focal cerebral ischemia/reperfusion and the underlying mechanism.Methods The acute focal cerebral ischemia/reperfusion models were established with suture emboli.Healthy male Sprague-Dawley rats were randomly divided into four groups: normal control group,sham group,IR group and PO group.There were 12 rats in each of the normal control group and the sham group.The IR group and PO group were further subdivided into subgroups and sacrificed 2 h,6 h,12 h,24 h,72 h and 7 d after ischemia/reperfusion(n=12).The volume of the infarction was observed by the TTC method;and the expression of Bcl-2 and Bax was determined by Western blotting to observe the protective effect of PO.Results ① TTC staining: there was no region of ischemia/reperfusion injury in the normal control group and the sham group.There was no region of ischemia/reperfusion injury in IR group and PO group 2 h after ischemia/reperfusion.At the time points of 6 h,12 h,24 h,72 h and 7 d after ischemia/reperfusion,there were statistical differences in mass percentage of the infracted regions between the PO group and the IR group(P0.05),and mass percentage of the infracted cerebral regions in the PO group was reduced as compared to the IR group.② Western-blotting: From the time point of 6h after reperfusion,in both PO group and IR group,the expression of Bcl-2 and Bax increased with time in the ischemia penumbra with peak expression at 12 h,and then decreased.The expression of Bax reached the peak at 24 h,and then decreased.Western-blotting analysis showed a gradual increase in Bcl-2 expression(P0.05) and a gradual decrease in Bax expression(P0.05) in PO group at each time point(6 h,12 h,24 h and 72 h after ischemia/reperfusion),compared with IR group.Conclusions ① PO can reduce the region of ischemia injury following focal cerebral ischemia/reperfusion injury;② PO can protect nerve cells by increasing the expression of Bcl-2 and decreasing the expression of Bax,following the cerebral ischemia/reperfusion injury.
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Background: Lipocalin-2 (LCN2) or neutrophil gelatinase-associated lipocalin (NGAL) is a small secreted adipokine associated with transport of small hydrophobic molecules [1]. In the liver, it limits bacterial growth and modulates the inflammatory response by acting as a “help me” signal attracting circulating blood cells into the tissue [2]. We have previously demonstrated that LCN2 is involved in control of hepatic fat metabolism by regulating the expression of the intracellular lipid droplet protein PLIN5/O'X'PAT [3].
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AIM: To investigate the relationship between apoptosis and pulmonary ischemia-reperfusion injury in rabbits and the intervention of tertram ethylpyrazine. METHODS: An in situ ischemia-reperfusion lung injury rabbit model was established in vivo. Apoptotic cells were explored by the terminal deoxynucleotidyl transferase-mediate dUTP nick-end labelling (TUNEL) technique. The index of quantitative assessment of histologic lung (IQA) was detected by Murata's way. The correlation was analyzed between the apoptosis and IQA of pulmonary ischemia-reperfusion injury. RESULTS: Obvious apoptosis of pneumocytes occurred at reperfusion 1, 3, and 5 h after 1 h ischem ia-reperfusion lung injury, and the peak was on 3h after reperfusion. The apoptotic cells decreased in TMP groups compared with IR groups. The values of IQA in IR group were significantly higher than those in TMP group (P0.01). There was a significant positive correlation between the apoptosis index and IQA (r=(0.718), P(0.01)). CONCLUSION: The apoptosis may significantly contribute to ischemia-reperfusion pulmonary injury and the tertram ethylpyrazine can protect PIRI by anti- apoptosis of pneumocytes.
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Most animal‐derived major allergens causing respiratory sensitization belong to the family of proteins called lipocalins. Their sequential identity varies but the three‐dimensional structure is conserved. They are present in body fluids and secretions. Several lipocalins are able to bind and transport small hydrophobic ligands like retinol. The immunological characteristics of lipocalin allergens are poorly known. Cow dust‐derived allergen, Bos d2, which is a potent inducer of IgE production, was observed to induce the weak proliferative responses of peripheral blood mononuclear cells of asthmatic patients upon stimulation in vitro . The responses were Th2‐deviated and directed to a few epitopes in Bos d2. One of the epitopes, situated adjacent to a structurally conserved region of lipocalins, was recognized by the T cells of all patients. Computer predictions suggested that human endogenous lipocalins may contain epitopes in the corresponding region. We have proposed that the allergenicity of lipocalins may be associated with the adaptation of the immune system to the presence of endogenous lipocalins.
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