• 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.

• 대한한방소아과학회지
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• 제25권1호
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• pp.40-48
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• 2011

Objectives: The purpose of this study is to evaluate the effect of Gonjadaesungchimjoongbang on spatial learning abilities and memories in ischemic brain injury. Methods: Rats were separated into three groups; (1) Normal, (2) Saline medication after ischemic brain injuries (control), (3) Gonjadaesungchimjoongbang medication after ischemic brain injuries (experiment). Ischemic brain injuries was induced by MCA occlusion and reperfusion. Morris water maze test was conducted for spatial learning and memory tests. Then, the change of BDNF in the hippocampus($7^{th}$, $14^{th}$ day) was examined by immunohistoche- mistry. Results: In Morris water maze test, spatial learning abilities and memory functioning were considerably increased in the experiment group as oppose to control group on $7^{th}$ and $14^{th}$ day(p<0.01). Moreover, immunohistochemistric response of BDNF in the hippocampus indicated that the more increased immune reaction was found in the experiment group as oppose to the control group on $7^{th}$ and $14^{th}$ day. Conclusions: Gonjadaesungchimjoongbang can improve the learning abilities and memories in ischemic brain injury.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.92-92
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• 1995

It has been suggested that oxygen-derived free radicals have an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothetized to exert its protective effect on NSAIDS-induced gastric injury by its antioxidant properties, Protect ive effect of taurine on indomethacin-induced gastric mucosal lesion and its protective mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats, Pretreatment with 0.25 g/kg of taurine for 3 days significantly reduced the gastric lesion formation and Inhibited the elevation of lipid peroxide level In gastric mucosa. Both resting and FMLP-induced luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment of indomethacin. 5-20mM of taurine inhibited chemiluminescence of neutrophils activated by indomethacin and/or FMLP. Human neutrophils (polymorphonuclear leukocytes) significantly adhered to confluent monolayer of human umbilical vein endothelial cells(HUVEC) after coincubation with aspirin or indomethacin. Also taurine prevented neutrophil adhesion induced by these drugs to HUVEC in dose-dependent manner. These results indicate that the protective effect of taurine against NSAIDS-induced gastric mucosal Injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.

• Journal of Yeungnam Medical Science
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• 제38권1호
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• pp.27-33
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• 2021

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

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

• 대한수의학회지
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• 제39권5호
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• pp.878-895
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• 1999

Ischemic preconditioing (IPC), i.e., a preliminary brief episode of ischemia and reperfusion, has been shown to reduce the cell damage induced by long ischemia and reperfusion. Superoxide radical which is produced during reperfusion after ischemia was recognized as a factor of the ischemic injury and it is dismutated into $H_2O_2$ and $O_2$ by two types of intracellular superoxide dismutase (SOD), Cu,Zn-SOD in cytoplasm and Mn-SOD in mitochondria. Recently oxygen free radicals are suggested to induce the apoptosis, however mechanism of the reduced apoptosis by ischemic preconditioing was unknown, while many studies performed in mammalian heart indicated that ATP-sensitive $K^+$ ($K_{APT}$) channel activation related with the protective effects. The aim of present study is to investigate 1) whether IP upregulate the Cu,Zn-SOD and Mn-SOD activities, and 2) whether ischemic preconditioning decreases apoptosis via $K_{APT}$ channel activation in timely reperfused skeletal muscle after long ishemia. The experimental animals, Sprague-Dawley rats weighing 250~300g, were divided into 8 groups; 1) control group, 2) ischemic preconditioning only groups, 3) pinacidil, a $K_{APT}$ channel opener, treatment only groups, 4) glibenclamide, a $K_{APT}$ channel blocker, treatment only groups, 5) ischemia groups, 6) ischemia after IPC groups, 7) ischemia and pinacidil treatment groups, and 8) IP and ischemia after glibenclamide pretreatment groups. Animals of the control group were administered with the vehicle (DMSO) alone. Pinacidil (1mg/kg) was administered intravenously 5 minutes after initiation of ischemia, and glibenclamide (0.5mg/kg) was injected intravenously 20 minutes before IPC. In rats that were ischemic preconditioned, the left common iliac artery was occluded for 5 minutes followed by 5 minutes of reperfusion by three times using vascular clamp. Ischemia was done by occlusion of the same artery for 4 hours. The specimens of left rectus femoris muscle were obtained immediately (0 hour), 12 hours, 24 hours after drug administrations, IP or ischemia and reperfusion. The immunoreactivities of SOD and its alterations were observed by use of sheep antihuman Cu,Zn-SOD and Mn-SOD antibodies on the $10{\mu}m$ cryosections. The incidencies of apoptosis were observed by TUNEL methods with in situ apoptosis detection kit on $6{\mu}m$ paraffine section. The results obtained were as follows : 1. After IPC, immunoreactivities of Cu,Zn-SOD mainly in the small-sized fibers were increased by 24 hours, that of Mn-SOD at 0 hour and 24 hours. 2. No significant changes in immunoreactivities of SOD was observed in the pinacidil and in the glibenclamide treatment only groups, and in the ischemia only groups. 3. The immunoreactivities of the Cu,Zn-SOD were increased in the ischemia after IPC groups and the ischemia and pinacidil treatment groups. 4. The immunoreactivities of the Cu,Zn-SOD in the IPC and ischemia after glibenclamide pretreatment groups were not increased except for the 12 hours reperfusion group. But, Mn-SOD immunoreactivities were increased in the 0 hours, 12 hours and 24 hours after reperfusion. 5. In the control group, the IPC only groups, and the pinacidil treatment only groups, negative or trace apoptotic reactions were observed, but the positive apoptotic reaction occured in the glibenclamide treatment groups. 6. Moderate or many number of apoptosis were revealed in the ischemia groups, and also the IPC and ischemia after glibenclamide pretreatment group except for 12 hours and 24 hours after reperfusion. However, the incidence of apoptosis was decreased in the ischemia after IPC groups and in the ischemia and pinacidil treatment groups. 7. There is a coincidence between the increase of Cu,Zn-SOD immunoreactivities and the decrease of apoptosis in the presence of ischemia and reperfusion. These results suggest that the protective effects of ishemic preconditioing may related to the SOD activation, and the ischemic preconditioning decreases the apoptosis partially via $K_{APT}$ channel activation in timely reperfused rat skeletal muscle. It is also suggested that inhibition of apoptosis by IPC may related with the SOD activation.

• Journal of Chest Surgery
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• 제29권8호
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• pp.850-860
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• 1996

활성산소는 동물실험에서 심근 재관류손상의 중요기전으로 알려져 있으나 실제 임상상황에서의 역할은 아직도 논란이 많다. 본 연구에서는 냉혈 심마비 액을 사용한 심근보호법을 이용하여 관상동맥우회술 을 시행받는 환자들을 대상으로 하여 심근허혈후 재관류시 활성산소에 의한 심근의 손상 정도 및 활성 산소 방어효소계의 변동과 그 기전을 규명하고자 하였다. 관상동맥우회술을 받는 환자(n=10)를 대상으로 하여 관상정 맥동 환류혈액 에서 상행대동맥 차단 전과 재관류 20분 후에 lactate dehydrogenase(LDH), creatinG phosphokinase MB 분획(CK-MB)과 malondialdehyde(MDA)의 농도를 측정하였으며 또한 같은 시각에 심근의 superoxide dismutase(SOD), catalase, glutathione peroxidase(GSHPX), glutathione reductase(GSSGRd) 그BT고 glucose 6- phosphate dehydrogenase(GGPDH)의 활성도를 측정하였다 관상정 맥동혈에서의 LDH(268 $\pm$40.3 to 448 $\pm$ 84.9 ml plasma)와 CK-MB(4.50$\pm$ 2.33 to 27.1$\pm$13.5 Ulml plasma)의 활성도 그리고 MDA(5.87$\pm$2.02 to 10.5$\pm$2.23 nmol/ml plsma)의 양은 상행대동맥 차단 전에 비하여 재관류 후에 현저히 증가하였으 \ulcorner심근의 SOD(13.5$\pm$4.04 to 20.7$\pm$8.56 mg protein), GSHPX(279 $\pm$)7.2 to 325$\pm$51.4 mU/mg protein) 그리고 GSSCRd(97.2$\pm$15.9 to 122 $\pm$25.1 m2/mg protein)의 활성도도 재관류후에 현저히 증가하였다 반면 심근의 catalase와GSPDH의 활성도는의미있는 변화가 없었다 한편 SOD에 대한 Western blot결과 Cu, Zn-SOD의 양이 현저하게 증가되었음을 관찰 하였다. 이상의 결과들로 관상동맥우회술시 상행대동맥차단에 따른 심근허혈후 재관류에 의하여 활성산소에 의한 산화성 심근손상이 일어나지만 동시에 활성산소 방어효소계의 활성 또한 증가됨으로써 심근손상 의 정도가 약화되었을 가능성을 추정할 수 있으며 이러한 활성산소 방어효소의 활성증가는효소단백의 광합성 증가에 의한 것으로 여겨진다.

• Tuberculosis and Respiratory Diseases
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• 제54권5호
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• pp.532-541
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• 2003

연구배경 : 장의 재관류로 발생하는 급성폐손상에서 group II $PLA_2$의 억제제로 알려진 doxycyclin의 치료효과와 그 작용기전을 알아보기 위하여 본 연구를 시행하였다. 특히 장의 재관류에 의한 급성폐손상이 호중구에 의한 산화성 스트레스에 의하며 이 과정에서 group II $PLA_2$가 관여한다는 사실에 근거하여 doxycyclin의 산화성 스트레스억제를 확인하는 것이 본 연구의 목적이었다. 방법 : 체중 300g 내외의 Sprague-Dawley 흰쥐에서 상장간막동맥을 60분간 clamp한 뒤 120분간의 재관류를 시키면 급성폐손상이 유도된다. 이때 호중구에 의한 산화성스트레스가 유발되고 여기에 $PLA_2$가 관여하는 것을 관찰하기위해 lung leak, lung MPO 활성도, CeCl3 cytochemical electron microscopy, cytochrome-c reduction assay 및 lung $PLA_2$ 활성도를 측정하였다. 또한 doxycyclin의 효과를 확인하기 위하여 doxycyclin hyclate(10mg/kg)를 복강내 주사한 뒤 위에서 언급한 모든 parameter를 측정, 비교하였다. 결과 : 장의 재관류로 유도된 급성폐손상에서 doxycyclin은 폐손상을 감소시켰는데 이것은 doxycyclin에 의한 lung MPO, 산소기생성, lung $PLA_2$ 활동도의 감소에 의한 것으로 생각되었다. 결론 : 장의 재관류로 유도된 급성폐손상은 호중구에서 생성되는 산소기, 특히 $PLA_2$의 활성화에 의해 생성된 산소기에 의한 것으로 생각되며 이때 doxycyclin은 $PLA_2$를 억제하여 산화성 스트레스를 감소시킴으로서 폐손상의 감소를 가져오는 것으로 생각된다.

• Journal of Chest Surgery
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• 제35권7호
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• pp.501-510
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• 2002

배경: 급성 호흡곤란증후군은 다양한 병인에 의해 발병하지만 그 병인론이 아직까지 확립되어 있지 않다. 본 연구에서는 장의 허혈-재관류시에 발병하는 급성 호흡곤란증후군에서 group II phospholipase $A_2$ ($PLA_2$)의 역할을 알아보기 위하여 시행되었다. 특히 폐장내의 호중구의 침윤과 더불어 유발되는 산화성 스트레스에서 group II $PLA_2$의 역할을 규명하려 하였다. 대상 및 방법: 체중 300g 내외의 Sprague-Dawley 종 흰쥐에서 급성 폐손상을 유발하기 위하여 상장간막동맥을 60분간 차단한 후 120분간 재관류를 시행하였다. Group II $PLA_2$가 폐장의 손상, 특히 혈관 내피세포의 손상에 미치는 영향을 호중구의 작용과 연관하여 알아보기 위하여 폐누출지수, 폐장내 myeloperoxidase의 활성도, 폐포세척액내의 단백함량을 측정하였다. 또한 장의 허혈-재관류에 따른 폐장내 $PLA_2$ 활성도의 변화를 검사하였고, 호중구에서의 산소기 형성에 미치는 group II $PLA_2$의 역할은 분리된 호중구에 rutin, manoalide, scalaradial과 같은 group II $PLA_2$ 억제제를 이용하여 산소기 생성이 억제됨을 확인함으로써 알아보았다. 장의 허혈-재관류에 따른 폐장 조직의 산화성 스트레스를 확인하기 위해 광학현미경법 및 cerium chloride를 이용한 세포화학적인 전자현미경법을 이용하여 폐장내 산소기의 생성을 확인하였다. 결과: 장의 허혈-재관류 후 폐장내 호중구의 침윤과 함께 급성 폐손상이 유발되었고, 폐장내 myeloperoxidase 활성도, 폐누출지수 및 폐세척액내의 단백함량이 대조군에 비해 유의하게 증가하였다(p<0.001). 폐장 및 장에서의 group II $PLA_2$ 활성도는 허혈-재관류 후 폐장, 장 모두에서 유의하게 증가하였고, rutin에 의해서 현저히 감소하였다(p<0.001). 사람의 혈액에서 분리된 호중구에서의 산소기 생성을 cytocrhome-c reduction assay를 통해 알아본 결과 rutin, manoalide, scalaradial 같은 group II PLA, 억제제에 의해 호중구의 산소기 생성이 감소함을 알 수 있었다. 허혈-재관류 후 광학현미경적 소견은 폐장내 염증세포의 침윤 및 모세혈관 주위의 부종이 관찰되었으나 rutin에 의해 이러한 변화는 억제되었다. $CeCl_3$을 이용한 세포화학적 전자현미경 실험에서 허혈-재관류 후 과산화수소의 생성이 증가하고 rutin에 의해서는 억제됨을 확인하였다. 결론: Croup II $PLA_2$의 억제는 침윤된 호중구로부터 산화기 생성을 억제함으로써 급성 폐손상을 완화하는 것으로 보이며, 따라서 group II $PLA_2$는 장 허혈-재관류로 유도된 급성 폐손상의 산화성 스트레스에서 중요한 역할을 하는 것으로 보인다.

• Journal of Chest Surgery
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• 제35권1호
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• pp.11-19
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• 2002

배경: 심장이식에 있어서 허혈-재관류 손상은 이식심장의 기능회복이나 장기생존을 좌우하는 중요한 요소이다. 본 연구에서는 세포질내의 NADH/NAD$^{+}$ 비율의 조절에 관여하는 피루브산염과 아스파라진산염을 현재 일반적으로 흔히 쓰이고 있는 장기 보존액인 위스콘신대학 용액에 첨가하여 심근을 보호하고 재관류 후의 심장 보존능의 효과를 증명하고자 하였다. 대상 및 방법: 생후 3일 이내의 신생돈의 심장을 4$^{\circ}C$ 위스콘신대학 용액(대조군, n=8)과 피루브산염과 아스파라진산염을 첨가한 위스콘신대학 용액(실험군, n=8)으로 심정지를 유도하여 적출하고 4$^{\circ}C$ 동일한 용액에서 24시간 동안 허혈상태로 보존한 후, 성돈을 교차순환 재관류혈 공급원으로 사용하여 좌심단순작업성 관류모델(left-sided working heart model)로 재관류 시킨 다음, 관류심장에서 일정한 시간 간격으로 박출작업계수(stroke work index)를 측정하였고, 관류가 끝난 후, 고 에너지 인산함유량(high-energy Phosphate stores), 심근의 수분 함유량(myocardial water content)을 측정하여 두 군을 비교하였다. 결과: 재관류가 시작되고 60분과 120분이 경과된 후에 좌심실 확장기말 압력(LVEDP)이 3, 6, 9, 및 12mmHg일 때 각각 박출작업계수를 측정하였는데, 60분이 경과된 후에 측정한 박출작업계수는 실험군에서 통계적으로 유의하게 높았고 [n=8, p<0.05, 대조군(16.3 $\pm$8.3$\times$1,000 erg/g) vs. 실험군(33.1 $\pm$ 15.1$\times$1,000 erg/g)], 120분이 경과된 후에도 실험군에서 통계적으로 유의하게 높게 나타났다 [n=8, p<0.05, 대조군(15.8$\pm$8.0$\times$1,000 erg/g) vs. 실험군(35.1$\pm$16.3$\times$l,000 erg/g)〕고 에너지 인산 중, AMP, ADP, 및 ATP의 함유량은 실험군에서 높게 측정되었다 [n=8, p<0.05, AMP -대조군(30.8$\pm$8.7 micromo1/g myocardium) vs. 실험군(53.1$\pm$11.1),ADP -대조군(52.6$\pm$7.3) vs. 실험군(91.3$\pm$20.9), ATP -대조군(67.5$\pm$23.8) vs. 실험군(156.5$\pm$45.8)]. 그러나, creatine phosphate 함유량 [n=8, p>0.05, 대조군(546.6$\pm$197.0 micromol/g myocardium) vs. 실험군(595.5$\pm$179.6) 과 심근 수분 함유량 [n=8, p>0.05, 대조군(87.2$\pm$5.5%) vs. 실험군(82.4$\pm$10.1)] 은 두 군간에 유의한 차이가 없었다. 결론: 이상의 결과는 피루브산염 와 아스파라진산염이 첨가된 위스콘신대학 용액이 위스콘신대학 용액만을 사용한 경우보다, 박출작업계수와 심근에너지 보존 측면에서 평가하기로는 심근보호 기능이 더 우수하다는 것을 나타내고 있다. 그리고, 대사과정에서 NADH/NAD$^{+}$의 대사와 관련이 없는 creatine phosphate의 보존에는 차이가 없다는 결과는 피루브산염과 아스파라진산염이 세포질내의 NADH/NAD$^{+}$의 조절에 관여하여 심근을 보호하리라는 가설을 가능하게 한다.