• 대한약리학회지
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• 제26권1호
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• pp.7-12
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• 1990

흰쥐로 부터 심장을 적출하여 Langendorff 관류장치에 현수하여 Krebs-Hensleit 영양액으로 분당 12ml속도로 30분간 관류시킨 후 관류 속도를 분당 1ml로 줄여(ischemia)60분간 관류시키면, 적출심장의 수축력이 현저히 감소되었고, resting tension이 현저히 증가되었다. 또 적출심장으로부터 유출되는 관류액의 250nm에서의 UV흡광치는 증가되었으며, 좌심실내의 칼슘의 농도는 대조군보다 상당히 증가되었다. 본 실험에서는 흰쥐에서 항염증작용, 혈압강하 및 서맥 작용, 평활근 및 심장근에서 근이완작용을 나타내는 cyclobuxine D의 ischemia에 의해 유도된 심장손상에 대한 보호효과를 관찰하였다. Cyclobuxine D(100ng/ml)는 ischemia에 의해 유발된 적출심장의 수축력 감소와 resting tension의 증가를 유의하게 억제하였으며, 심장으로부터의 ATP metabolites의 유출과 좌심실내의 칼슘 축적을 억제시켰다. 이상의 결과는 Cyclobuxine D가 ischemia에 의해 유발된 손상으로 부터 심장을 보호할 수 있음을 나타내며, 이는 cyclobuxine D의 심장세포내의 칼슘 유입 억제작용에 기인하는 것으로 사려된다.

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.1-9
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• 2010

AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.

• Toxicological Research
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• 제13권4호
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• pp.359-365
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• 1997

Many factors are known to be responsible for cerebral ischemic injury, such as excitatory neurotransmitters, increased intraneuronal calcium, or disturbance of cellular energy metabolism. Recently, oxygen free radicals, formed during ischemia/reperfusion, have been proposed as one of the main causes of ischemia/reperfusion injury. Therefore, to investigate the role of oxygen free radical during ischemia/reperfusion, in the present study the effect of endogenous oxygen free radical scavenger, superoxide dismutase / catalase(SOD / catalase) on the release of [$^3$H]-5-hydroxytryptamine([$^3$H]-5-HT) during hypoxia/reoxygenation in rat hippocampal slices was measured. The hippocampus was obtained from the rat brain and sliced 400 gm thickness with manual chopper. After 30 min's preincubation in the normal buffer, the slices were incubated for 20 min in a buffer containing [$^3$H]-5-HT(0.1 $\mu$M, 74 $\mu$Ci) for uptake, and washed. To measure the release of [$^3$H]-5-HT into the buffer, the incubation medium was drained off and refilled every ten minutes through a sequence of 14 tubes. Induction of hypoxia for 20 min (gassing it with 95% N$_2$/5% CO$_2$) was done in the 6th and 7th tube, and oxygen free radical scavenger, SOD / catalase was added 10 minutes prior to induction of hypoxia. The radioactivity in each buffer and the tissue were counted using liquid scintillation counter and the results were expressed as a percentage of the total activity. When slices were exposed to hypoxia for 20 min, [$^3$H]-5-HT release was markedly decreased and a rebound release of [$^3$H]-5-HT was observed on the post-hypoxic reoxygenation period. SOD / catalase did not changed the release of [$^3$H]-5-HT in control group, but inhibited the decrease of [$^3$H]-5-HT release in hypoxic period and rebound increase of [$^3$H]-5-HT in reoxygenation period. This result suggest that superoxide anion may play a role in the hypoxic-, and reoxygenation-induced change of [$^3$H]-5-HT release in rat hippocampal slices.

• Journal of Ginseng Research
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• 제47권2호
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• pp.274-282
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• 2023

Background: Ginsenoside compound K (CK) stimulated activation of the PI3K-Akt signaling is one of the major mechanisms in promoting cell survival after stroke. However, the underlying mediators remain poorly understood. This study aimed to explore the docking protein of ginsenoside CK mediating the neuroprotective effects. Materials and methods: Molecular docking, surface plasmon resonance, and cellular thermal shift assay were performed to explore ginsenoside CK interacting proteins. Neuroscreen-1 cells and middle cerebral artery occlusion (MCAO) model in rats were utilized as in-vitro and in-vivo models. Results: Ginsenoside CK interacted with recombinant human PTP1B protein and impaired its tyrosine phosphatase activity. Pathway and process enrichment analysis confirmed the involvement of PTP1B and its interacting proteins in PI3K-Akt signaling pathway. PTP1B overexpression reduced the tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) after oxygen-glucose deprivation/reoxygenation (OGD/R) in neuroscreen-1 cells. These regulations were confirmed in the ipsilateral ischemic hemisphere of the rat brains after MCAO/R. Ginsenoside CK treatment reversed these alterations and attenuated neuronal apoptosis. Conclusion: Ginsenoside CK binds to PTP1B with a high affinity and inhibits PTP1B-mediated IRS1 tyrosine dephosphorylation. This novel mechanism helps explain the role of ginsenoside CK in activating the neuronal protective PI3K-Akt signaling pathway after ischemia-reperfusion injury.

• Molecules and Cells
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• 제42권9호
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• pp.672-685
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• 2019

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.

• Journal of Chest Surgery
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• 제27권7호
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• pp.563-570
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• 1994

Effect of ischemic preconditioning on left ventricular function after cardiac arrest in isolated rat heart.Ischemic preconditioning reduces infarct size caused by sustained ischemia. However, the effects of preconditioning on post ischemic cardiac function are not well-known. The objective of the present study was to determine whether preconditioning would improve the recovery of left ventricular functions after cardiac arrest in isolated rat heart model.Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to either 5 minutes of global, normothermic transient ischemia [Group 2 and 4] or not [Group 3]. A stabilization period of perfusion lasting 5 minutes after the termination of transient ischemia was followed by a standard global, normothermic 20 minute-ischemia and 35-minute reperfusion challenge [Group 3 and 4]. These following results were odtained.1. The recovery of left ventricular developed pressures showed no significant differences between Group 3 and Group 4 at 50 [P>0.3] and 85 minute [P>0.2].2. Heart rates showed no significant differences throughout all the course of experiment and between groups [P>0.5].3. The recovery of left ventricular maximum dP/dt showed no significant differences between Group 3 and Group 4 at 50 [P>0.1] and 85 minute [P>0.2].4. The recovery of pressure-rate products showed no significant differences between Group3 and Group 4 at 50 [P>0.5] and 85 minute [P>0.1].These results suggest that ischemic preconditioning does not provide significant benefit for the postischemic left ventricular functions in isolated rat hearts.

• The Korean Journal of Pain
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• 제23권1호
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• pp.1-10
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• 2010

Background: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. Methods: The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. Results: Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. Conclusions: The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2001년도 공동 춘계학술대회
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• pp.85.2-85
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• 2001

No Abstract, See Full Text

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.145-152
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• 2017

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (non-cardiac) increases the tolerance of the myocardium to sustained ischemia-reperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

• Journal of Korean Neurosurgical Society
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• 제39권4호
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• pp.300-302
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• 2006

"Stunning" represents prolonged contractile depression of any muscular component after alleviation of severe ischemia, as shown in reperfusion following acute myocardial ischemia or ischemic stroke. Clinically, it presents with no or delayed recovery past to thrombolytic therapy but its pathogenic mechanism is not fully uncovered yet. We describe a unique case of a 63-year-old woman, who was undertaken endovascular coiling for the aneurysms, deteriorated several hours later without known cause, and showed delayed clinical improvement over the next 3 days following thrombolysis. Immediate post-thrombolysis magnetic resonance imaging scan showed no apparent abnormality except for high signal intensity within the corresponding hemisphere. Reversible but delayed nature of " brain stunning" can be explained by these images and it seems to be caused by a certain type of reperfusion injury.