• Biomolecules & Therapeutics
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• 제25권3호
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• pp.272-278
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• 2017

Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-${\alpha}$), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.

• Archives of Reconstructive Microsurgery
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• 제14권2호
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• pp.85-94
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• 2005

Purpose: This study was to evaluate the effect of ${\alpha}-lipoic$ acid, a potent free radical scavenger, on the expression of active form of extracellular signal-regulated kinase (pERK1/2) proteins from hindlimb muscles of rats following ischemia-reperfusion injury. Material and methods: 64 health, $280{\sim}350\;g$ weighted Sprague-Dawley male rats were used. In order to make a muscle flap, the gastrocnemius (GC) and soleus (SOL) muscles were dissected and elevated. The popliteal artery was occluded for 4hours and reperfused for 10 minutes, 30 minutes, 1 hour, 2 hours and 4 hours, respectively. Results: The ischemia by occlusion of the popliteal artery itself caused a minimal change in expression of phosphorylated form of proteins observed in hindlimb muscle. In contrast, after 4 hours of ischemia, immunoreactivity for pERK1/2 in the GC muscle showed dual peaks at 10 minutes and 4 hours after reperfusion. In ${\alpha}-lipoic$ acid treated group, the expression of pERK1/2 was increased significantly compared to I/R-only group. Conclusion: These results suggest that ${\alpha}-lipoic$ acid may protect I/R injury of the skeletal muscle through free radical scavening and activation of intracellular pERK1/2 expression.

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.413-423
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• 2021

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague-Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

• Korean Circulation Journal
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• 제53권6호
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• pp.387-403
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• 2023

Background and Objectives: Myocardial ischemia and reperfusion injury (MIRI) has high morbidity and mortality worldwide. We aimed to explore the role of long noncoding RNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in cardiomyocyte pyroptosis. Methods: Hypoxia/reoxygenation (H/R) injury was constructed in human cardiomyocyte (HCM). The level of LOXL1-AS1, miR-761, phosphatase and tensin homolog (PTEN) and pyroptosis-related proteins was monitored by quantitative real-time polymerase chain reaction or western blot. Flow cytometry examined the pyroptosis level. Lactate dehydrogenase (LDH), creatine kinase-MB and cardiac troponin I levels were detected by test kits. Enzyme-linked immunosorbent assay measured the release of inflammatory cytokines. Dual-luciferase assay validated the binding relationship among LOXL1-AS1, miR-761, and PTEN. Finally, ischemia/reperfusion (I/R) animal model was constructed. Hematoxylin and eosin staining assessed morphological changes of myocardial tissue. NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and casepase-1 expression was determined by immunohistochemistry. Results: After H/R treatment, LOXL1-AS1 and PTEN were highly expressed but miR-761 level was suppressed. LOXL1-AS1 inhibition or miR-761 overexpression increased cell viability, blocked the release of LDH and inflammatory cytokines (interleukin [IL]-1β, IL-18), inhibited pyroptosis level, and downregulated pyroptosis-related proteins (ASC, cleaved caspase-1, gasdermin D-N, NLRP3, IL-1β, and IL-18) levels in HCMs. LOXL1-AS1 sponged miR-761 to up-regulate PTEN. Knockdown of miR-761 reversed the effect of LOXL1-AS1 down regulation on H/R induced HCM pyroptosis. LOXL1-AS1 aggravated the MIRI by regulating miR-761/PTEN axis in vivo. Conclusions: LOXL1-AS1 targeted miR-761 to regulate PTEN expression, then enhance cardiomyocyte pyroptosis, providing a new alternative target for the treatment of MIRI.

• Journal of Korean Neurosurgical Society
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• 제67권2호
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• pp.186-193
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• 2024

Objective : The treatment paradigm for acute ischemic stroke has undergone several major changes in the past decade, contributing to improved patient prognosis in clinical practice. However, the extent to which these changes have affected patient prognosis in the real-world is yet to be clarified. This study aimed to evaluate the real-world impact of modern reperfusion therapy for acute ischemic stroke using data from the National Health Insurance Service in Korea. Methods : This study included patients aged 18-80 years who were admitted via the emergency room with an I63 code between 2011 and 2020. The rates of intravenous thrombolysis use and endovascular treatment according to the year of admission were investigated. Furthermore, the rates of decompressive craniectomy and 3-month mortality were also analyzed. The 10-year observational period was divided into three periods based on the 2015 guideline change as follows : prior, 2011-2014; transitional, 2015-2016; and modern, 2017-2020. Results : A total of 307117 patients (mean age, 65.7±10.9 years) were included, and most patients were male (59.7%). The rate of endovascular treatment gradually increased during the study period from 0.71% in the prior period to 1.32% in the transitional period and finally to 1.85% in the modern period. Meanwhile, the 3-month mortality rate gradually decreased from 4.78% in the prior period to 4.03% in the transitional period and to 3.71% in the modern period. Conclusion : In Korea, the mortality rate decreased as the rate of modern reperfusion therapy increased in patients with acute ischemic stroke. Overall, technical and scientific advances in reperfusion therapy have improved the outcome of patients with acute ischemic stroke in Korea.

• Korean Journal of Radiology
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• 제21권1호
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• pp.101-107
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• 2020

Objective: Avoiding a catastrophic outcome may be a more realistic goal than achieving functional independence in the treatment of acute stroke in octogenarians. This study aimed to investigate predictors of catastrophic outcome in elderly patients after an endovascular thrombectomy with an acute anterior circulation large vessel occlusion (LVO). Materials and Methods: Data from 82 patients aged ≥ 80 years, who were treated with thrombectomy for acute anterior circulation LVO, were analyzed. The association between clinical/imaging variables and catastrophic outcomes was assessed. A catastrophic outcome was defined as a modified Rankin Scale score of 4-6 at 90 days. Results: Successful reperfusion was achieved in 61 patients (74.4%), while 47 patients (57.3%) had a catastrophic outcome. The 90-day mortality rate of the treated patients was 15.9% (13/82). The catastrophic outcome group had a significantly lower baseline diffusion-weighted imaging-Alberta stroke program early CT score (DWI-ASPECTS) (7 vs. 8, p = 0.014) and a longer procedure time (42 minutes vs. 29 minutes, p = 0.031) compared to the non-catastrophic outcome group. Successful reperfusion was significantly less frequent in the catastrophic outcome group (63.8% vs. 88.6%, p = 0.011) compared to the non-catastrophic outcome group. In a binary logistic regression analysis, DWI-ASPECTS (odds ratio [OR], 0.709; 95% confidence interval [CI], 0.524-0.960; p = 0.026) and successful reperfusion (OR, 0.242; 95% CI, 0.071-0.822; p = 0.023) were independent predictors of a catastrophic outcome. Conclusion: Baseline infarct size and reperfusion status were independently associated with a catastrophic outcome after endovascular thrombectomy in elderly patients aged ≥ 80 years with acute anterior circulation LVO.

• Journal of Chest Surgery
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• 제36권12호
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• pp.894-903
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• 2003

체내에서 발생하는 산화 질소는 허혈-재관류에 따른 폐혈관 저항을 감소시키고 혈관의 미세 투과도를 줄이고 세포손상을 방지하여 이식 후 폐장 기능의 보전에 도움이 된다고 알려져 있으나, 산화질소 자체의 세포독성으로 인해 재관류 동안 폐 부종을 오히려 증가시킬 수도 있다고 한다. 저자들은 산화 질소의 공여물질인 nitroglycerin을 투여한 분리 폐장 관류 모델을 이용하여 폐장 보존에 이점과 단점을 동시에 가지고 있는 산화질소가 허혈-재관류 과정에서 폐장의 기능에 미치는 영향을 알아보기 위하여 본 연구를 시행하였다. 대상 및 방법: Sprague-Dawley종의 수컷 흰쥐 35마리를 사용하였다. Nitroglycerin (NTG)군(n=18)은 NTG를 정맥 주사하고 University of Wisconsin용액에 혼합하여 폐장 관류를 시행하였고, 대조군(n=17)은 NTG 대신 같은 양의 생리 식염수를 사용하였다. 구득한 심폐블록을 1$0^{\circ}C$에서 24시간 동안 보관한 후, 분리 폐장 관류 모델에서 인체 혈액을 Krebs-Hensleit용액으로 희석하여 60분간 재관류하였다. 재관류하는 동안 기도내압과 페동맥압을 지속적으로 측정하였고, 관류후 30분과 60분에 혈액 내 산소와 이산화탄소 분압을 측정하였다. 재관류가 끝난 후 기관지폐포세척을 통해 폐포 내 단백함량을 측정하였으며, 중성구 침착 정도를 알기 위해 myeloperoxidase (MPO) 활성도를 측정하였다. 걸과: 두 군 간의 기도내압과 폐동맥압은 통계적으로 유의한 차이는 없었으나, NTG군에서 관류기간 중 폐동맥압이 상대적으로 낮게 유지되는 경향이 있었다. 이산화탄소 분압, 기관지폐포세척액 내의 단백질 함량, MPO의 활성도는 두 군에서 유의한 차이는 없었으나, 산소 분압은 NTG 군에서 통계적으로 유의하게 높게 나타났다(p<0.05). 전자현미경 검사에도 대조군에 비해 NTG군에서 폐포구조, 폐포상피세포, 모세혈관배열 등 미세구조의 손상이 적게 나타났다. 결론. 폐장 구득전 NTG의 투여는 폐장의 기능과 미세구조의 유지에 도움이 된다고 판단되며, 임상 폐이식에도 적용이 가능하리라 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제46권4호
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• pp.512-522
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• 1999

연구배경: 공여폐에 관류 후 보존 과정에서 야기될 수 있는 형태학적 변화와 재관류를 시행한 후 초래될 수 있는 폐조직의 변화를 광학 및 전자현미경으로 검색하여 폐이식 전후 과정에서 초래될 수 있는 폐 손상의 형태화적 변화를 관찰하고자 본 연구를 실시하였다. 방 법: 실험 재료로는 한국산 성견 46마리를 사용하여 공여견과 수용견으로 나눈다음 공여견에서 폐관류, 폐보존 및 재관류 과정 후 폐조직을 각각 채취하여 형태학적 검색을 하였다. 결 과: 광학현미경 소견에서 폐관류에 의한 조직손상은 매우 경미하였다. 전자현미경 소견에서 폐포 모세혈관은 불규칙하고, 혈관 내피세포에 종창은 뚜렷하지 않았다. 폐보존 후에는 광학현미경 소견에서 폐포허탈과 경화가 폐관류 군에 비하여 더욱 뚜렷하게 보였고 부분적으로 폐간질 부위가 비후 되었다. 전자현미경 소견에서 폐포 허탈이 뚜렷하면서 I 형 폐포상피세포의 종창 및 파괴와 파괴산물이 폐포내로 유리되었고, 대식세포의 탐식이 현저하였다. 폐포 모세혈관 내피세포는 종창, 수포형성 및 혈관 내로 촉각모양 돌기를 관찰할 수 있었다. 재관류후 광학현미경 관찰에서 폐실질의 허탈과 경화가 뚜렷하여 저배율에서 쉽게 볼 수 있었고 폐포 구조의 심한 변형과 폐간질 조직의 비후가 현저하였다. 전자현미경 소견에서 I 형 폐포상피세포는 종창, 수포형성 및 파괴를 보였고 폐포 내로 파괴산물이 자주 보였다. II 형 상피세포의 세포질 내에는 다층판체의 수가 감소하고 내용물은 비어 있었다. 폐포모세혈관들은 그 형태가 매우 불규칙하였으며 내피세포에서 다수의 수포형성과 종창을 보였고, 혈관 내에는 파괴산물과 촉각모양 돌기가 뚜렷하게 보였다. 폐간질 부위는 종창으로 미만성 비후를 보였다. LPDG용액에 VP와 PGE1을 함께 사용한 군에서는 폐조직의 변화가 정미하였으나 MEC 용액에 VP와 PGE1을 사용한 군에서는 폐포 상피세포와 폐포 모세혈관 내피세포의 변화가 보다 현저하였다. 결 론: 이상의 실험 결과를 토대로 관류에 의한 폐조직 변화는 경미하였고, 보존 후에는 관류군에 비해서 폐조직 손상이 더욱 뚜렷하였다. 채관류 후에는 관류 및 보존 과정보다 훨씬 심한 형태학적 변화를 보였는데 이들 변화는 급성 폐손상의 초기 병변에 해당되었다. 따라서 공여폐에 사용할 적절한 보존액 개발과 함께 보존 및 재관류과정에서 초래되는 조직 손상을 최소화하는 기술 개발이 폐이식의 성공률을 높이는 데 중요한 요소가 될 것으로 생각된다.

• Journal of Acupuncture Research
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• 제27권4호
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• pp.29-38
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• 2010

Objectives : The purpose of the study is to determine the neuroprotective effect of modified Boyanghwano-tang(mBHT), a traditional Korean medicine, on the transient focal cerebral ischemia in rats. Methods : Focal ischemia and reperfusion were induced by middle cerebral artery occlusion(MCAO) for 90 min, followed by 144 h reperfusion in rats. mBHT(200mg/kg body weight, p.o.) was administrated in rats once a day during reperfusion. At the end of treatment, brain infarction was measured by TTC staining, and histological change was observed by H&E staining. The expressions of Bax, Bcl-2 and cytochrome c in ischemic brains were determined by immunofluorescent analysis. Results : mBHT significantly reduced the cerebral infarct volumes of the MCAO rats. mBHT also attenuated the neuronal cell death and the expressions of pro-apoptotic molecules, bax and cytochrome c in ischemic brains. Further, mBHT significantly increased the survival time of ischemeic rats and the expression of anti-apoptotic molecule, Bcl-2 in ischemic brains. Conclusions : Our results suggest that mBHT is neuroprotective and may prove to be useful adjunct in the treatment of ischemic stroke.

• 한국임상약학회지
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• 제3권2호
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• pp.147-155
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• 1993

The cardiac effects of PAF antagonist Ginkgolide B(BN 52051) have been investigated on the isolated perfused guinea pig hearts maintained at the constant hydrostatic perfusion pressure of 80 cm water. PDE(Phosphodiesterase) inhibitor KR-30289 was used as a positive control to see the positive inotropic effects on the perfused hearts. In this expriments, Ginkgolide $B(10^{-5}-SM)$ showed negative inotropic effects by decreasing of LVP, LVDP, LV dp/dt, HR and RPP(Rate Pressure Product). Ginkgolide B also decreased the number of extrasystole by $51.9\%(from\;23.75\pm9.22/min\;to\;11.43\pm435/min)$ induced by global ischemia and reperfusion. The rate, [-dp/dt]/[+dp/dt] increased in preischemia but decreased in postischemia. 1n the separated study the injection of 1ml of Ginkgolide B$(10^{-4M})$ on the isolated heart, increased coronary flow(CF) by $11.8\%(from\;7.5\pm7.65ml/min\;to\;8.5\pm0.29ml/min)$ and decreased the number of extrasystole by $47.6\%(from\;21\pm5.92/min\;to\;11\pm5.27/min)$. In conclusion, Ginkgolide B showed antiarrhythmic and protective effects by decreasing the number of extrasystole and by increasing the coronary flow, respectively.