• Journal of Microbiology and Biotechnology
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• 제31권8호
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• pp.1069-1078
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• 2021

Sevoflurane postconditioning (SPostC) has been proved effective in cardioprotection against myocardial ischemia/reperfusion injury. It was also reported that heat shock protein 70 (HSP70) could be induced by sevoflurane, which played a crucial role in hypoxic/reoxygenation (HR) injury of cardiomyocytes. However, the mechanism by which sevoflurane protects cardiomyocytes via HSP70 is still not understood. Here, we aimed to investigate the related mechanisms of SPostC inducing HSP70 expression to reduce the HR injury of cardiomyocytes. After the HR cardiomyocytes model was established, the cells transfected with siRNA for HSP70 (siHSP70) or not were treated with sevoflurane during reoxygenation. The lactate dehydrogenase (LDH) level was detected by colorimetry while cell viability and apoptosis were detected by MTT and flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect HSP70, apoptosis-, cell cycle-associated factors, iNOS, and Cox-2 expressions. Enzyme-linked immuno sorbent assay (ELISA) was used to measure malondialdehyde (MDA) and superoxide dismutase (SOD). SPostC decreased apoptosis, cell injury, oxidative stress and inflammation and increased viability of HR-induced cardiomyocytes. In addition, SPostC downregulated Bax and cleaved caspase-3 levels, while SPostC upregulated Bcl-2, CDK-4, Cyclin D1, and HSP70 levels. SiHSP70 had the opposite effect that SPostC had on HR-induced cardiomyocytes. Moreover, siHSP70 further reversed the effect of SPostC on apoptosis, cell injury, oxidative stress, inflammation, viability and the expressions of HSP70, apoptosis-, and cell cycle-associated factors in HR-induced cardiomyocytes. In conclusion, this study demonstrates that SPostC can reduce the HR injury of cardiomyocytes by inducing HSP70 expression.

• Journal of Korean Neurosurgical Society
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• 제29권9호
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• pp.1171-1178
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• 2000

Objective : The purpose of the present study was to determine the appropriate time of clinical intervention by observing and analyzing the changes in the size of infarct, penumbra and cerebral edema and the extend of neurological deficit due to reperfusion damage according to time in a reversible cerebral ischemic model of reperfusing blood flow after inducing ischemia by maintaining middle cerebral artery occlusion for 2 hours(h) in rats. Methods : The rats were divided according to reperfusion time into control group(0 h reperfusion time) and experimental groups(0.5, 1, 2, 3, 4, 5, 6, 12, and 24 h of reperfusion time). Results : Changes in the size of infarction due to reperfusion damage were 0.93, 1.48 and 1.16% at 0.5, 1 and 2 h after reperfusion, respectively, and although a statistical significance was not present compared to 1.35% of the control group, damages increased drastically up to 6 h(6.64%), and the size increased were 6.65 and 6.78% at 12 and 24 h, respectively. Also there was no significant difference after 6 h up to 24 h in the size of infarction. In the areas where infarction occurred, reperfusion damage increased significantly with time in cortex than in subcortex. Accordingly, the size of penumbra area also showed a statistically significant decrease from 2 h up to 6 h after reperfusion, and 6 h after reperfusion, the area almost disappeared, becoming permanent infarction. Thus, reperfusion damage showed a significant increase from 2 h up to 6 h after reperfusion, and became steady thereafter. As for the mean ratio of the extend of cerebral edema, the control group and reperfusion 0.5 h group were 1.073 and 1.081, respectively ; up to 2 h thereafter, the ratio decreased to 1.01 but increased again with time ; and in reperfusion 12 h and reperfusion 24 h, the ratios were 1.070 and 1.075, respectively, showing similar size with that of control group. As for neurological deficit scores, the score of the control group was 2.67, that of reperfusion 2 h was 2, those of reperfusion 3 h and 6 h groups were 3.2 and 3.8, respectively, and those of reperfusion 12 h and 24 h groups were 4.2 and 4.6, respectively. Thus, as for the test results, the neurological deficit increased with time 2 h after reperfusion, and in reperfusion 12 and 24 h groups, almost all the symptoms appeared. Conclusion : As shown in these results, although the changes in the size of infarction due to reperfusion damage did not increase up to 2 h after reperfusion in the experimental groups compared to the control group, damage increased significantly thereafter up to 6 h, and the size remained about the same from 6 h to 24 h after reperfusion, becoming permanent infarction ; thus, the appropriate time of intervention according to the present study is at least 6 h before after maintaining reperfusion, including the time of cerebral artery occlusion.

• Biomolecules & Therapeutics
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• 제21권6호
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• pp.454-461
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• 2013

The neuroprotective effects of a butanol fraction of white rose petal extract (WRPE-BF) were investigated in a middle cerebral artery occlusion (MCAO) model. Seven week-old male rats were orally administered WRPE-BF for 2 weeks and subjected to MCAO for 2 h, followed by reperfusion. Twenty-four h later, MCAO-induced behavioral dysfunctions were markedly improved in a dose-dependent manner by pretreatment with WRPE-BF. Moreover, higher dose of WRPE-BF not only decreased infarction area but also effectively reduced astrogliosis. The expression of inducible nitric oxide synthase, cyclooxygenase-2, and glial fibrillary acidic protein in MCAO model were markedly inhibited by WRPE-BF treatment. Notably, WRPE-BF decreased nitricoxide and malondialdehyde levels in the striatum and subventricular zone of stroke-challenged brains. These data suggested that WRPE-BF may exert its neuroprotective effects via anti-oxidative and anti-inflammatory activities against ischemia-reperfusion brain injury and could be a good candidate as a therapeutic target for ischemic stroke.

• Journal of Chest Surgery
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• 제54권1호
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• pp.9-16
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• 2021

Background: The deposition of monomeric C-reactive protein (mCRP) in the myocardium aggravates ischemia-reperfusion injury (IRI) and myocardial infarction. Ischemic preconditioning (IPC) is known to protect the myocardium against IRI. Methods: We evaluated the effects of IPC on myocardium upon which mCRP had been deposited due to IRI in a rat model. Myocardial IRI was induced via ligation of the coronary artery. Direct IPC was applied prior to IRI using multiple short direct occlusions of the coronary artery. CRP was infused intravenously after IRI. The study included sham (n=3), IRI-only (n=5), IRI+CRP (n=9), and IPC+IRI+CRP (n=6) groups. The infarcted area and the area at risk were assessed using Evans blue and 2,3,5-triphenyltetrazolium staining. Additionally, mCRP immunostaining and interleukin-6 (IL-6) mRNA reverse transcription-polymerase chain reaction were performed. Results: In the IRI+CRP group, the infarcted area and the area of mCRP deposition were greater, and the level of IL-6 mRNA expression was higher, than in the IRI-only group. However, in the IPC+IRI+CRP group relative to the IRI+CRP group, the relative areas of infarction (20% vs. 34%, respectively; p=0.079) and mCRP myocardial deposition (21% vs. 44%, respectively; p=0.026) were lower and IL-6 mRNA expression was higher (fold change: 407 vs. 326, respectively; p=0.376), although the difference in IL-6 mRNA expression was not statistically significant. Conclusion: IPC was associated with significantly decreased deposition of mCRP and with increased expression of IL-6 in myocardium damaged by IRI. The net cardioprotective effect of decreased mCRP deposition and increased IL-6 levels should be clarified in a further study.

• Toxicological Research
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• 제18권3호
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• pp.267-273
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• 2002

Fructose 1,6-diphosphate(FDP), a glycolytic metabolite, is reported to ameliorate inflammation and inhibit the nitric oxide production in murine macrophages stimulated with endotoxin. It is also reported that FDP has cytoprotective effects against hypoxia or ischemia/reperfusion injury in brain and heart, and may play a protective role in ultraviolet B (UVB, 280~320 nm)-injured keratinocyte by attenuating prostaglandin (PG)-E$_2$production and cyclooxygenase (COX)-2 expression, which are possibly through blocking the intracellular reactive oxygen species (ROS) accumulation. Therefore FDP is considered to act as a potent antioxidant especially in the skin. We conducted the several safety tests (single-dose toxicity, primary skin irritation test, eye irritation test, skin sensitization test, phototoxicity test, photosenitization test and human patch test) to see if FDP is safe in case used for the skin application. Our data obtained hitherto suggest that FDP is very safe if applied to the skin.

• 한국임상수의학회:학술대회논문집
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• 한국임상수의학회 2007년도 추계국제학술대회 및 컨퍼런스
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• pp.564-564
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• 2007

• Bulletin of the Korean Chemical Society
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• 제30권11호
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• pp.2621-2625
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• 2009

To identify a non-acylguanidine NHE-1 inhibitor, an acylguanidne group was replaced with an imidazole group in the potent NHE-1 inhibitors with furan or benzothiphene core template, found from our previous studies. We synthesized and biologically evaluated 4-heteroaryl-2-amino-5-methylimidazole derivatives. All those imidazole compounds (16-18) represented the potent NHE-1 inhibitory activities, similar to the corresponding acylguanidine compounds.

• 한국임상수의학회지
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• 제18권4호
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• pp.358-362
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• 2001

Brain dead (BD) patients remain the largest source of solid organs for transplantation. BD has shown to decrease graft function and survival in rodent models. The aim of this study was to evaluate how brain death affects graft viability in the donor and kidney tolerance to cold preservation as assessed by survival in a canine transplantation. 13 Beagle dogs were used for the study. Brain death was induced by the sudden inflation of a subdural balloon catheter with continuous monitoring of arterial blood pressure and eletroencephalographic activity (n=3). Sixteen hours after conformation of brain death, kidney graft were retrieved (n=6). Non-BD donors served as controls (n=4). All kidneys were flushed with University of Wisconsin (UW) solution and preserved for 24 hours at 4$^{\circ}C$ before transplantation. Recipient survival rates, serum creatinine level were analyzed. Brain death induced the well-known Cushing reaction with a severe increase in blood pressure and tachycardia. Thereafter, cardiac function returned progressively to baseline within 8 hours and remained stable until the end of the experiment. All of dogs in both group transplanted were survived until 7 days (100%), and the kidneys showed functional early rejection at 8.3$\pm$0.5 days and 8.5$\pm$0.5 days after transplantation, in BD and allograft group, respectively. BD kidneys were functionally similar to control kidneys for 7 days after transplantated. Brain death has no deleterious effect on preservation injury and survival of dog kidney transplantation, although it induces changes in hemodynamic parameters. This study reveals that kidneys from BD donors do not exhibit more ischemia reperfusion injury, and support good early function and survival.

• Journal of Chest Surgery
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• 제30권6호
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• pp.573-579
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• 1997

지난 30년동안 장기이식분야의 괄목할만한 발전과 더불어 국내에서도 신장, 간 등은 물론 심장이식도 활 발히 이루어지고 있다. 그러나 폐 이식만은 많은 제약으로 인하여 답보상태를 면하지 못하고 있으며 그중에 서도 장기공여자의 부족과 상대적으로 허혈-재관류손상에 예민한 폐 자체의 보존시간의 문제가 가장 먼저 해결해야 할 과제로 여겨지고 있다. 일반적으로 폐는 허혈에 견딜수 있는 시간이 4-6시간으로 알려져 있으 며 많은 연구자들이 더 좋은 폐보존방법을 연구하고 평가하기 위한 실험모델을 개발하여 왔다. 그러나 많 은 실험모델의 등장으로 같은 실험도 서로 상반되는 결과를 낳고 있으며 각각의 모델이 가진 단점들로 인 하여 실험모형의 표준화와 결과분석의 기준을 정하는데 있어 완벽한 모델은 정립된 것이 없는 상태이다. 폐 보존후 기능에 영향을 미칠 수 있는 요인들 즉 허혈성 보존기간, 보존 온도, 폐관류액치 구성성분 등 을 분석하는데는 비교적 간단하고, 경비가 적게 들며 실험결과의 신뢰도가 높은 새로운 모형의 개발이 요 구 되었다. 이에 서울대학교병원 흉부외과에서는 빠르게 변화하는 폐 보존 방법의 실험 및 한국에서는 거 \ulcorner이루어지지 않고 있는 폐 보존 방법에 대한 통계 자료를 확보하여 폐 이식 수술에 이를 적용하고자, 연 구노력 끝에 토끼 폐장으로 상기 목적에 적합한 폐장 분리관류 모형을 완성하였다.

• Journal of Ginseng Research
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• 제48권4호
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• pp.395-404
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• 2024

Background: Ginsenoside Rg₁ (Rg₁) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg₁ has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood. Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg₁ against myocardial ischemia (MI) were screened and explored. Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg₁ against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg₁ intervention on H9c2 cells injured by H₂O₂ showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg₁ on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg₁ was also evaluated. Conclusion: Rg₁ can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg₁, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.