고양이를 이용한 허혈성 전조건 모델에서 KATP 통로 활성화와 단상성 활동전압기의 변화에 의한 심보호효과

박종선(Jong Seon Park),신동구(Dong Gu Shin),김영조(Young Jo Kim),심봉섭(Bong Sup Shim) 대한내과학회 1999 대한내과학회지 Vol.57 No.1

This study was designed to evaluate the role of KATP channel activation and change of monophasic action potential duration on cardioprotective effect of ischemic preconditioning in cat. Methods : 34 cats were divided into 4 groups: control (n=10), ischemic preconditioning(n=8), glibenclamide pre- treated(n=8) and nicorandil pre-treated group(n=8). Ischemic preconditioning was done in ischemic preconditioning and glibenclamide pre-treated groups by 3 episodes of 5 min ischemia and 10 min reperfusion. All subjects underwent 40 min of ischemia and 40 min reperfusion. The KATP channel antagonist glibenclamide was given as intravenous bolus (0.5mg/kg) 10 min before ischemic precondtioning and infused (5μg/min) during ischemic preconditioning. Nicorandil, a KATP channel opener was injected as intravenous bolus (0.5mg/kg) before 40 min ischemic procedure. Monophasic action potential duration at 50% repolarization(MAP50) was measured in the ischemic and non-ischemic area respectively by epicardial probe throughout the experiment. The effects of ischemic preconditioning were determined by infarct size (% area at risk). Results : Ischemic preconditioning or pretreatment with nicorandil prior to 40 min ischemia demonstrated a significant reduction in infarct size(26.6±7%, 33±8% infarction of the risk zone, respectively, p<0.01, p<0.05 vs. control) with respect to control(42±7% infarction of the risk zone). Pretreatment with glibenclamide abolished the effect of ischemic preconditioning(40±8% infarction of the risk zone, p=NS vs. control) Ischemic preconditioning group exhibited a significant reduction of ischemic area MAP50 duration in the ischemic area during preconditioning; at first preconditioning 123±9msec vs. 137±19msec control(p=NS), at second preconditioning 105±16msec vs. 140±19msec control(p<0.01), at third preconditioning 109±15msec vs. 138±19msec control(p<0.05). Pretreatment with glibenclamide prevented the reduction of MAP50 in the ischemic area during ischemic preconditioning. During 40 minutes ischemia, MAP50 shortening was more pronounced in the preconditioned group than in control group; at 10 min 85±22 msec vs. 131±31msec control(p<0.05), at 20 min 88±21msec vs. 130±32msec control(p<0.05), and at 30 min 103±24msec vs. 136±30msec control(p<0.05). This shortening effect was prevented by glibenclamide pretreatment. Nicorandil pretreatment pronounced the ischemic shortening of MAP50 in ischemic area and the nicorandil effect was most significant during early ischemic period; at 10 min 97±21msec(p<0.05 vs. control), at 20 min 104±32msec (p=NS vs. control), and at 30 min 134±28msec(p=NS vs. control). MAP50 measured in non-ischemic area was not significantly different between groups. Conclusion : We conclude that KATP channel activation and monophasic action potential duration shortening play a important role in myocardial protection during ischemic injury.

토끼의 혀혈성 전처치 모델(Ischemic Proconditioning Model)에서 Heat Shock Protein 70의 발현양상과 초산화물 불균등화 효소(Superoxide Dismutase)와의 관계

윤종현,윤호중,전희경,유기동,백상홍,정욱성,채장성,김재형,최규보,홍순조 대한순환기학회 1999 Korean Circulation Journal Vol.29 No.9

왼온엉덩동맥에서의 짧은 허혈과 재관류 횟수에 따른 흰쥐 신장에서의 전염증성 사이토카인의 발현 변화

박현주(Hyun Joo Park),김원규(Wonkyu Kim),윤지희(Jee Hee Youn),백두진(Doo Jin Paik) 대한체질인류학회 2007 대한체질인류학회지 Vol.20 No.1

이 실험은 다리에서 짧은 허혈 횟수의 증가와 재관류 경과시간에 따라 멀리 위치한 신장에서 나타나는 NF-κB와 전염증성 사이토카인, 세포간부착분자의 발현 변화를 알아보기 위하여 실시하였다. 35주령의 Sprague-Dawley계 수컷 흰쥐를 사용하여 대조군과 허혈양상화군으로 나누었고, 허혈양상화 처치는 왼온엉덩동맥에서 5분 허혈과 5분 재관류를 3회, 6회, 10회 실시하였다. 재관류 직후와 3시간, 6시간, 24시간, 72시간 경과 후 왼쪽 신장을 적출하여 세포자멸사를 관찰하고, NF-κB, TNF-α, IL-1β, ICAM-1 단백질에 대한 면역조직 화학염색과 Western blot 분석을 하여 다음과 같은 결과를 얻었다. 허혈양상화 처치군에서는 처치 횟수가 증가될수록, 재관류 24시간 경과 후 사망률이 높아졌다. NF-κB는 재관류 0시간부터 24시간까지는 허혈양상화를 10회 처치한 군에서 가장 높게 발현했으나, 72시간에서는 3회 처치군에서 가장 높게 발현하였다. TNF-α는 재관류 0시간과 6시간, 24시간, 72시간에서는 허혈양상화를 10회 처치한 군에서 가장 높게 발현했으나, 3시간에는 모든 처치군이 비슷한 면역반응을 보였다. IL-1β와 ICAM-1은 모든 재관류 시간에 허혈양상화를 10회 처치한 군에서 가장 높게 발현하였다. 바깥속질에서의 세포자멸사는 모든 재관류 시간에 허혈양상화를 10회 처치한 군에서 비율이 가장 크게 나타났다. 흰쥐 신장에서 허혈 및 재관류 손상에 관여되는 NF-κB와 TNF-α, IL-1β, ICAM-1의 발현은 왼온엉덩동맥에서 허혈양상화를 3회와 6회 처치시 감소되었으나, 10회 처치시에는 증가되어 허혈손상을 증가시키는 것으로 생각되었다. The purpose of this study is to investigate the changes in NF-κB and proinflammatory cytokines expression following courses of reperfusion after various cycles of ischemic preconditioning in the rat kidney. Thirty five weeks old Sprague Dawley rats were subjected to 3, 6 and 10 cycles of ischemic preconditioning that composed of 5 min ischemia and 5 min reperfusion at the left common iliac artery using rodent vascular clamp. The left kidney obtained after 0, 3, 6, 24 and 72 hours of reperfusion followed by each cycle. The expression patterns of NF-κB, TNF-α, IL-1β and ICAM-1 were detected by immunohistochemical staining and Western blotting methods. Apoptosis were detected by TUNEL assay. The results were as follows; In the ischemic preconditioning group, the mortality increased from 24 hours after reperfusion when cyclic episodes of short ischemia and reperfusion were increased. The highest level of NF-κB expression in outer medulla of the kidney from 0 hr to 24 hrs of reperfusion is detected after 10 cycles of ischemic preconditioning. The highest level of NF-κB expression at 72 hrs of reperfusion is revealed after 3 cycles of ischemic preconditioning. The highest level of TNF-α expression in outer medulla of the kidney at 0 hr and 6, 24, 72hrs of reperfusion is shown after 10 cycles of ischemic preconditioning. After 3 hrs of reperfusion, all ischemic preconditioning groups shows similar expression. The highest level of IL-1β and ICAM-1 expression in outer medulla of the kidney is observed at all of reperfusion times after 10 cycles of ischemic preconditioning. The highest level of apoptosis in rat kidney outer medulla at all of reperfusion times is shown after 10 cycles of ischemic preconditioning. In conclusion, 3 or 6 times of remote ischemic preconditioning in the common iliac artery could reduce the expression of NF-κB, TNF-α, IL-1β, and ICAM-1. However, more than 10 times of remote ischemic preconditioning increased ischemia-reperfusion injury, caused by increased expression of NF-κB, TNF-α, IL-1β, and ICAM-1.

Preconditioning으로서의 운동이 탈진적 운동시 항산화 기능 및 운동수행능력에 미치는 효과

채창훈(Chae Chang-Hun),이상규(Lee Sang-Kyu),박석(Park Sok) 한국체육과학회 2010 한국체육과학회지 Vol.19 No.2

The effects of exercise as preconditioning on antioxidant function and exercise performance ability at during maximal exercise are pooly understood This study was investigated the exercise as preconditioning on antioxidant function and exercise performance ability. Mail sprague-Dawley rats(n=24) were randomly divided into the following 3 groups; (1) none preconditioning group(CON: n=8), (2) exercise as preconditioning for 10 minute (Pre 10min: n=8), (3) exercise as preconditioning for 20 minute (Pre 20min: n=8), Rats were subjected to swimming exercise for 5days a week for 4weeks before maximal exercise. At the end of exercise as preconditioning period, rats were performanced maximal exercise. We got the following result for antioxidant function and maximal exercise performance effect by exercise as preconditioning. In rats with skeletal muscle(gastrocnemius) induced SOD, CAT activity and reduced MDA concentration. In addition, exercise performance time were increased. These result suggest that exercise as preconditioning in the animal model, may be useful to improve antioxidant function and exercise performance ability.

Mechanisms and Prospects of Ischemic Tolerance Induced by Cerebral Preconditioning

Mohammad Iqbal Hossain Bhuiyan,김연정 대한배뇨장애요실금학회 2010 International Neurourology Journal Vol.14 No.4

In the brain, brief episodes of ischemia induce tolerance against a subsequent severe episode of ischemia. This phenomenon of endogenous neuroprotection is known as preconditioning-induced ischemic tolerance. The purpose of this review is to summarize the current state of knowledge about mechanisms and potential applications of cerebral preconditioning and ischemic tolerance. Articles related to the terms ischemic preconditioning and ischemic tolerance were systematically searched via MEDLINE/ PubMed, and articles published in English related to the nervous system were selected and analyzed. The past two decades have provided interesting insights into the molecular mechanisms of this neuroprotective phenomenon. Although both rapid and delayed types of tolerance have been documented in experimental settings, the delayed type has been found to be more prominent in the case of neuronal ischemic tolerance. Many intracellular signaling pathways have been implicated regarding ischemic preconditioning. Most of these are associated with membrane receptors, kinase cascades, and transcription factors. Moreover, ischemic tolerance can be induced by exposing animals or cells to diverse types of endogenous and exogenous stimuli that are not necessarily hypoxic or ischemic in nature. These cross-tolerances raise the hope that, in the future, it will be possible to pharmacologically activate or mimic ischemic tolerance in the human brain. Another promising approach is remote preconditioning in which preconditioning of one organ or system leads to the protection of a different (remote) organ that is difficult to target, such as the brain. The preconditioning strategy and related interventions can confer neuroprotection in experimental ischemia, and, thus, have promise for practical applications in cases of vascular neurosurgery and endo-vascular therapy.

허혈성 전처치의 심근 보호효과: 심근세포내 당원량과 Protein Kinase C 사이의 관계

김호덕,김현,라봉진,김명호,김철우,김혜원,김대중,김영배 대한순환기학회 2001 Korean Circulation Journal Vol.31 No.1

Delayed Neuroprotective Effect of Isoflurane Preconditioning on Brain Ischemia in Gerbils

Jung-Wook Park,Young-Kyu Choi,Hyub Huh,Jae-Woo Yi,Bong-Jae Lee,Il-Gyu Ko,Sung-Eun Kim,Mal-Soon Shin,Hong Kim,Dong-Hee Kim,Chang-Ju Kim 대한스트레스학회 2011 스트레스硏究 Vol.19 No.1

허혈성 뇌손상은 뇌졸중과 외상성 뇌손상을 유발하는 병태생리적 기전이다. 허혈 전처리(ischemic preconditioning, IPC)는 이러한 허혈 손상에 대해 효과적인 보호작용을 미치는 것으로 생각된다. 본 연구에서는 isoflurane (ISO)의 전처리가 뇌허혈 유발 모래쥐의 해마 CA1에서의 신경세포사멸과 기억력에 미치는 영향을 연구하였다. 전처리 방법으로, ISO 처치군의 모래쥐들은 뇌허혈을 유도하기 1시간 전에 4.2% (2.0 MAC) isoflurane을 30분 동안 흡입하도록 하였으며, 뇌허혈은 총경동맥을 5분 동안 폐색시킴으로써 유발하였다. 뇌허혈 유발 6일 후에 모래쥐들을 희생시켰다. 실험결과, ISO 전처리는 허혈에 의한 기억력 감퇴를 경감시켰으며, 세포사멸의 표지자들인 terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)과 caspase-3의 발현을 감소시켰다. 이러한 결과는 ISO 전처리가 해마의 CA1 부위에서의 신경세포사멸을 억제함으로써, 허혈에 의한 기억력 손상을 예방할 수 있음을 의미한다. 따라서, ISO 전처리는 허혈성 뇌손상을 감소시키는 효과적인 방법으로 사용될 수 있을 것이다. Ischemic brain injury is the underlying pathophysiology of stroke and traumatic brain injury. Ischemic preconditioning (IPC) with anesthetics has been considered to be an effective method for protecting organs against ischemic insult. In the present study, we investigated the delayed effect of isoflurane (ISO) preconditioning on memory ability and apoptotic neuronal cell death in the hippocampal CA1 region following transient global ischemia in gerbils. One hour before the induction of brain ischemia, the gerbils in the ISO-treated groups were subjected to inhalation of 4.2% (2.0 MAC) isoflurane for 30 min as a method of preconditioning. Global ischemia was induced by occlusion of common carotid arteries for 5 min. The gerbils were sacrificed 6 days after surgery. In the present study, ISO preconditioning prevented the ischemia-induced decrease in the latency of the step-down avoidance task. ISO preconditioning also reduced the ischemia-induced increase in the numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive and caspase-3-positive cells. These results demonstrated the possibility that ISO preconditioning prevents ischemia-induced memory impairment by inhibiting apoptotic neuronal cell death in the hippocampal CA1 region. In this study, we demonstrated that ISO preconditioning is an effective method of reducing ischemic brain injury during the delayed phase. (Korean J Str Res 2011;19:61∼68)

허혈 조건부여가 심근기능의 회복에 미치는 영향 : 적출 심장모델을 이용한 실험연구 Isolated heart experimental study

백광제,김준식,한승백,전영진,이인성 大韓應急醫學會 1999 대한응급의학회지 Vol.10 No.2

Background: Brief episode of coronary artery occlusion(i.e.,ischemic preconditioning) makes the heart more resistant to injury from a subsequent ischemic insult. Although a great deal of effort has been made in studying ischemic preconditioning, the underlying mechanism of ischemic preconditioning and its effect on hypothermic insult has not been elucidated. This study was performed to see whether ischemic preconditioning protects against the depression of cardiac contractility induced by hypothermic cardioplegic arrest/reperfusion. And recently, adenosine was known to have some correlation with the mechanism of preconditioning. If so, does this effect remain after the blockade of adenosine receptor by 8-phenyl theophyline? Method: Twenty-four Sprague-Dawley rat weighed 250-350g were used and divided into three groups. Rat hearts were removed rapidly, and each isolated heart paced with a rate of 180/min was perfused by modified Krebs-Hensleit buffer(KHB) solution on a Langendorff apparatus for an hour. After obtaining baseline data including left ventricular pressure(LVP), dp/dt, and coronary flow, cardiac arrest was induced by perfusion of 0℃ crystalloid cardioplegic(St Thomas) solution. After that, all hearts were stored in the same St Thomas solution at same temperature for 2 hours. In group Ⅰ(control group), the heart was reperfused by KHB solution. In group Ⅱ(preconditioning group), the heart was subjected to two 2-minute episode of global ischemia followed by 5 minute reperfusion with KHB solution(preconditioning) before cardiac arrest. In group Ⅲ(phenyl theophylline group), the heart was subjected to preconditioning procedure and 8-phenyl theophylline at 10μM in concentration was added to KHB solution at time of reperfusion. Observing parameter was obtained in each group at 10, 20, 40 and 60 minutes after starting reperfusion and compared statistically by use of one way ANOVA test(STASTICA, release 4.5). p-value less than 0.05 was considered significant. Results: Although depressed LVP, dp/dt, and coronary flow were seen in all groups during the reperfusion period, the preconditioned group showed more effective recovery of LVP than that of the control group, especially at 10, 20 and 40 minutes(p<.05). We failed to demonstrate the difference between the phenyl theophylline group and the control group(p=NS). Conclusion: These results suggest that ischemic preconditioning has protective effect on recovery state of hypothemic cardioplegic arrest/reperfusion. Its protective effect was limited during early reperfusion stage and was blocked by adenosine blocker.

Involvement of Ceramide in Ischemic Tolerance Induced by Preconditioning with Sublethal Oxygen-Glucose Deprivation in Primary Cultured Cortical Neurons of Rats

Bhuiyan, Mohammad Iqbal Hossain,Islam, Mohammad Nurul,Jung, Seo Yun,Yoo, Hye Hyun,Lee, Yong Sup,Jin, Changbae Pharmaceutical Society of Japan 2010 Biological & pharmaceutical bulletin Vol.33 No.1

<P>The complex molecular cascades of ischemic tolerance in brain cells remain unclear. Recently, sphingolipid-related metabolite ceramide has been implicated as a second messenger in many biological functions, including neuronal survival and death. The present study, therefore, examined the roles of ceramide (Cer) in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation (OGD) using primary cultured cortical neurons of rats. Preconditioning of the neurons with sublethal 1-h OGD produced robust neuroprotection against cell death induced by lethal 3-h OGD imposed 12 h after preconditioning when measured by the MTT assay. Analysis of sphingolipids using LC-MS/MS showed that the ischemic preconditioning resulted in significant increases in the levels of C<SUB>16 : 0</SUB> Cer, C<SUB>18 : 0</SUB> Cer, C<SUB>20 : 0</SUB> Cer, C<SUB>24 : 0</SUB> Cer, C<SUB>24 : 1</SUB> Cer and the total ceramide contents compared with the sham-washed control group. However, sphingomyelin contents were not significantly changed by the ischemic preconditioning, suggesting that ceramides were increased through the <I>de novo</I> synthetic pathway. In the case of severe OGD paradigm, levels of ceramide and sphingomyelin in the lethal OGD group were not significantly different from those of the control group or the lethal OGD group with preconditioning at any time points studied. Treatment with an inhibitor of <I>de novo</I> ceramide synthesis, fumonisin B<SUB>1</SUB>, during the ischemic preconditioning period completely blocked preconditioning-induced ischemic tolerance. Moreover, application of a non-cytotoxic concentration of exogenous cell-permeable ceramide produced neuroprotection against lethal OGD. The results suggest that ceramides increased by sublethal OGD preconditioning play an important role in induction of ischemic tolerance.</P>

일시적 허혈의 반복에 의해 유도된 산소유리기에 대한 심장보호기전에 대한 연구

이인훈,박희주 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.6