• 한국임상수의학회지
• /
• 제24권2호
• /
• pp.94-98
• /
• 2007

돼지에서 신장의 허혈-재관류 손상의 감소에 대한 비타민 C와 E의 영향을 알아보기 위하여 본 연구를 실시하였다. 돼지 10두를 2개의 군으로 구분하여, 60분 동안 체온과 같은 허혈을 한쪽 신장에 유발하고 반대쪽 신장은 절제하였다. 처치군은 수술 2일전 비타민 C와 E를 이틀 동안 전처치하고, 그 뒤에 수술 중 비타민 C와 heparin이 첨가된 생리식염수를 관주-흡인하였다. 대조군은 heparin이 첨가된 생리식염수의 관주-흡인만을 하였다. Blood urea nitrogen, creatinine 및 antioxidant superoxide dismutase (SOD)를 측정하기 위하여 수술 전, 수술 후 1, 3, 7, 14일에 혈액 샘플을 채취하였다. 수술 후 14일에 안락사를 시키고, 병리조직검사를 위하여 신장을 적출하였다. BUN은 대조군과 처치군 사이에 수술 후 1일, 3일 또는 7일에 유의성이 있는 차이가 인정되었다. (p<0.05). Creatinine은 대조군과 처치군 사이에 수술 후 3일에 유의성이 있는 차이가 인정되었다. (p<0.05). 혈장에서의 항산화 효소의 활성은 대조군과 처치군 사이에서 수술 후 14일에 유의성이 있는 차이가 인정되었다. (p<0.05). 병리조직 검사 결과에서 처치군이 대조군 보다 더 적은 신장 세뇨관에서의 손상의 정도를 보였다. 비타민 C와 E는 돼지에서 신장의 허혈-재관류 손상을 감소시켰다.

• Journal of Chest Surgery
• /
• 제31권8호
• /
• pp.739-748
• /
• 1998

연구배경: 재관류 없이 허혈 심근세포의 기능이나 형태학적 변화를 원래의 상태로 회복시킬 수 없음은 주 지의 사실이나 재관류가 반드시 유익하지만은 않다는 실험결과들이 있으므로 국소적으로 일과성 허혈을 유도하여 심근세포에서 일어나는 형태학적 변화를 관찰하고 재관류가 허혈심근에 미치는 영향을 알아보고자 하였다. 재료 및 방법: 생후 12개월 내외의 홀슈타인종 소를 사용하여 정맥 마취하에서 흉부를 열고 왼쪽 관상동맥 의 전하방 가지를 20분 동안 결찰하여 국소허혈을 유도하고 결찰을 풀어 재관류를 유도하였다. 위험부위의 심근조직 을 재관류 직후, 재관류후 1, 2, 3, 6, 12시간 및 재관류 12시간후 1시간동안 보조호흡과 수액공급만을 한 후 각각 생검하여 통상적인 방법으로 처리하여 투과전자현미경으로 관찰하였다. 결과: 20분 동안의 국소허혈로 심근세포는 경도에서 중등도에 이르는 미세구조적 변화들이 나타났는데 특히 세포막하, 핵, 사립체, 심근원섬유 등의 소기관에서 많은 변화들이 관찰되었다. 그러나 재관류를 시작하여 1시간이 지나면 허혈심근세포에서는 회복을 시사하는 소견들이 나타나기 시작하였으며 미세혈관 내에서 혈전형성이나 내강의 협착 등이 관찰되었으나 재관류가 계속됨에 따라 심근세포의 미세구조적 변화들은 서서히 회복되어 가는 양상을 나 타내었다. 그러나 시간이 경과함에 따라 심내막하 심근세포의 일부에서는 재관류 손상으로 추측되는 미세구조적 변 화들이 관찰되었다. 결론: 이상의 결과로 미루어 미세혈관은 허혈에 대한 저항력이 심근세포보다 강하며 허혈 심근세포는 재관류 없이는 회복될 수 없고, 회복에는 비교적 장시간이 요구되며, 따라서 혈관폐쇄로 인한 허혈시 혈관성형술이나 혈전 용해를 촉진하는 물질을 이용한 치료는 타당성이 있는 것으로 생각되나 재관류 유발성 세포손상에 대한 주의가 요망 된다.

• Biomolecules & Therapeutics
• /
• 제17권3호
• /
• pp.270-275
• /
• 2009

Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke.

• The Korean Journal of Physiology and Pharmacology
• /
• 제2권6호
• /
• pp.753-761
• /
• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• Journal of Korean Neurosurgical Society
• /
• 제58권6호
• /
• pp.508-512
• /
• 2015

Background : Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. Methods : We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. Results : After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. Conclusion : In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53.

• Journal of Ginseng Research
• /
• 제46권4호
• /
• pp.515-525
• /
• 2022

Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca²⁺]_i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca²⁺]_i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

• Nutrition Research and Practice
• /
• 제8권4호
• /
• pp.391-397
• /
• 2014

BACKGROUND/OBJECTIVE: Myocardial cell death due to occlusion of the coronary arteries leads to myocardial infarction, a subset of coronary heart disease (CHD). Dietary fiber is known to be associated with a reduced risk of CHD, the underlying mechanisms of which were suggested to delay the onset of occlusion by ameliorating risk factors. In this study, we tested a hypothesis that a beneficial role of dietary fiber could arise from protection of myocardial cells against ischemic injury, manifested after occlusion of the arteries. MATERIALS/METHODS: Three days after rats were fed apple pectin (AP) (with 10, 40, 100, and 400 mg/kg/day), myocardial ischemic injury was induced by 30 min-ligation of the left anterior descending coronary artery, followed by 3 hr-reperfusion. The area at risk and infarct area were evaluated using Evans blue dye and 2,3,5-triphenyltetrazolium chloride (TTC) staining, respectively. DNA nicks reflecting the extent of myocardial apoptosis were assessed by TUNEL assay. Levels of cleaved caspase-3, Bcl-2, and Bax were assessed by immunohistochemistry. RESULTS: Supplementation of AP (with 100 and 400 mg/kg/day) resulted in significantly attenuated infarct size (IS) (ratio of infarct area to area at risk) by 21.9 and 22.4%, respectively, in the AP-treated group, compared with that in the control group. This attenuation in IS showed correlation with improvement in biomarkers involved in the apoptotic cascades: reduction of apoptotic cells, inhibition of conversion of procaspase-3 to caspase-3, and increase of Bcl-2/Bax ratio, a determinant of cell fate. CONCLUSIONS: The findings indicate that supplementation of AP results in amelioration of myocardial infarction by inhibition of apoptosis. Thus, the current study suggests that intake of dietary fiber reduces the risk of CHD, not only by blocking steps leading to occlusion, but also by protecting against ischemic injury caused by occlusion of the arteries.

• Journal of Ginseng Research
• /
• 제47권3호
• /
• pp.408-419
• /
• 2023

Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng, has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury. Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis. Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury. Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2 mediated mitochondrial dynamics and bioenergy.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.148.1-148.1
• /
• 2003

The effects of methanolic extracts of Polygalae Radix (PR 100mg/kg) was tested to evaluate on the neuroprotective activity (92％ p<0.001) on global cerebral schemia. Based on bioassays guided fractionation, butanol soluble fraction (BtOH 25mg/kg) had the neuroprotive effect (87％ p<0.001) of global cerebral ischemia in rat. Oxygen free radical injury plays an important role in neuronal damage induced by brain ischemia and reperfusion. (omitted)

• 한국자원식물학회:학술대회논문집
• /
• 한국자원식물학회 2021년도 춘계학술대회
• /
• pp.57-57
• /
• 2021

Oxygen glucose deprivation/re-oxygenation (OGD/R) induces neuronal injury via mechanisms that are believed to mimic the pathways associated with brain ischemia. Stachys sieboldii Miq. (Chinese artichoke), which has been extensively used in oriental traditional medicine to treat of ischemic stroke; however, the role of S. sieboldii Miq. (SSM) in OGD/R induced neuronal injury is not yet fully understood. The present research is aimed to investigate the protective effect and possible mechanisms of SSM extract treatment in an in vitro model of OGD/R to simulate ischemia/reperfusion Injury. Pretreatment of these cells with SSM significantly attenuated OGD/R-induced production of reactive oxygen species (ROS) by increasing GPx, SOD, and decreasing MDA. SSM decreased mitochondrial damage caused by OGD/R injury and inhibited the release of cyt-c from mitochondrion to cytoplasm in SH-SY5Y cells. Furthermore, neuronal cell apoptosis caused by OGD/R injury was inhibited by SSM, and SSM could decrease apoptosis by increasing ratio of Bcl-2/Bax and inhibiting caspase signaling pathway in SH-SY5Y cells. SSM demonstrated a neuroprotective effect on the simulated cerebral ischemia in vitro model, and this effect was the inhibition of mitochondria-mediated apoptosis pathway by scavenging of ROS generation. Therefore, SSM may be a promising neuroprotective strategy against ischemic stroke.