• 대한한의학회지
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• 제22권4호
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• pp.142-150
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• 2001

Objectives : The purpose of this investigation is to evaluate and compare the effects of Sunghyangjunggi-san (SH) and Gwackhyangjunggi-san (GH) extracts on reperfusion following the MCA occlusion in rats. Methods : To evaluate the effect of Sunghyangjunggi-san (SH) and Gwackhyangjunggi-san (GH) extracts on reperfusion following the MCA occlusion, the volume of cerebral infarction and edema were measured and the change of the CA1 pyramidal neurons in the hippocampus were investigated by light microscopy. Results : 1. The infarction volume of the control group was 23.6%, that of the GH group was 23.7%, and that of the SH group was 18.5%. 2. The brain edema volume of the control group increased by 16% compared with that of the normal group, that of the GH group increased by 14%, and that of the SH group increased by 9%. 3. The number of surviving pyramidal neurons in the CAI area of the hippocampus was investigated under light microscopy. In the control group, few surviving pyramidal neurons excisted (mean 6.4) and similarly in the GH group (mean 8.5), but in the SH group, the number of surviving pyramidal neurons was significantly higher, to the mean 18.4. Conclusions : According to the above results, in regard to the damage of neurons following cerebral ischemia, the GH group has little effect of the protection of neurons compared to the control group, but the SH group has a remarkable effect.

• BMB Reports
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• 제43권9호
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• pp.629-634
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• 2010

Endotoxin including lipopolysaccharide (LPS) confers organ tolerance against subsequent challenge by ischemia and reperfusion (I/R) insult. The mechanisms underlying this powerful adaptive defense remain to be defined. Therefore, in this study we attempted to determine whether nitric oxide (NO) and its associated enzymes, inducible NOS (iNOS) and endothelial NOS (eNOS, a constitutive NOS), are associated with LPS-induced renal tolerance against I/R injury, using iNOS (iNOS knock-out) or eNOS (eNOS knock-out) gene-deleted mice. A systemic low dose of LPS pretreatment protected kidney against I/R injury. LPS treatment increased the activity and expression of iNOS, but not eNOS, in kidney tissue. LPS pretreatment in iNOS, but not eNOS, knock-out mice did not protect kidney against I/R injury. In conclusion, the kidney tolerance to I/R injury conferred by pretreatment with LPS is mediated by increased expression and activation of iNOS.

• Journal of Chest Surgery
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• 제25권2호
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• pp.131-136
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• 1992

The effect of temperature of cardioplegic solution on myocardial preservation was studied using isolated rat heart perfusion technique. Twenty Sprague-Dawley rats, weighing 120~140gm, were pretreated with intraperitoneal injection of heparin sodium[300u/kg] and then the hearts were excised after cervical herniation 30 minutes later. The hearts were perfused in isolated working heart apparatus with oxygenated modified Tyrode solution at 37oC. After 10 minutes of non working heart perfusion, the hearts were subjected to arrest for 30 minutes by administration of 5cc cardioplegic solution at the temperature of 4oC [Group I ], 15oC [Group II], 25oC [Group III], 37oC[Group IV]. At the same time, the topical cooling of heart was performed using ice saline. After arrest, the hearts were reperfused by non working heart perfusion for 1 hour with modified Tyrode solution at 37oC. The CPK, GOT and LDH in reperfusate were measured at 5,20,40,60 minutes after start of reperfusion. With the values of those, we compared the effect of temperature of cardioplegic solution on myocardial preservation. The results were as follows; 1. The enzyme values in reperfusate were highest at 5 minute and after then declined. 2. At 5 minutes after reperfusion, the enzyme values in Group I were lower than those in other Groups. These results suggest that the cardioplegic solutions using for cardiac arrest and myocardial protection can be working better at 4oC than at any other temperature.

• 식품보건융합연구
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• 제5권4호
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• pp.25-28
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• 2019

Now a days problem in health has become common. So, instead of curing them, prevention through dietary supplements has proven to be useful. In the case of patients who have already developed the disease atleast relieving pain and suffer is a challenging thing. In this context L- arginine is doing better compared to other essential aminoacids up to some extent. Arginine was found to reduce the pain associated with pulmonary hypertension foun to be associated with sickle cell anaemia. It also reduces the reperfusion injury after ischemia, trauma and shock. Some of the drugs with L-arginine as component are under clinical trials and hope to be available in the market soon. Severe preeclampsia is characterised by headaches, blurred vision, and inability to have high photovision, nausea and vomiting. L-Arginine along with Vit C and E are given as medical food to the patients and decrease in condition symptoms is the project now under phase II clinical trial. However the role of arginine in ameolirating preeclampsia symptoms is uncertain except with that of hypertension. Arginine is used to treat pain in sickle cell anaemia, lung damage, reperfusion injury, Trauma and shock but should be excluded during sepsis.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.664-668
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• 2002

KR-31543,(2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran is a new neuroprotetive agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.

• Molecules and Cells
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• 제40권8호
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• pp.542-549
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• 2017

Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.225-234
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• 2018

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of $K_{ATP}$ channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

• 대한본초학회지
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• 제28권2호
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• pp.1-7
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• 2013

Objectives : Sesamin, a major lignan in sesame seeds, has been reported to have neuroprotective effects against in vitro ischemia and in vivo MCAo-reperfusion cerebral ischemia model, however, there is no reports in an in vivo global cerebral ischemia model. The purpose of the study was to investigate the neuroprotective effect of sesamin in global cerebral ischemia induced by four-vessel occlusion (4-VO) in rats through inhibition of microglial activation in this model. Methods : The neuroprotective effects were investigated using a 10 min of 4-VO ischemia rat model by measuring intact pyramidal neurons in the CA1 region of the hippocampus using Nissle staining. The antiinflammatory or reducing neurotoxicity effect was investigated using immunohistochemisty, RT-PCR and western blot analysis of inflammatory or neurotoxic mediators. Results : Intraperitoneal injection of sesamin at doses of 0.3, 1.0, 3.0, and 10.0 mg/kg at 0 min and 90 min after ischemia conferred 26.6%, 30.1%, 42.5%, and 30.5% neuroprotection, respectively, compared to the vehicle-treated control group. A 3.0 mg/kg dose of sesamin inhibited microglia activation and consequently, cyclooxygenase-2, inducible nitric oxide, and interleukine-$1{\beta}$ expressions at 48 h after reperfusion. Conclusions : Sesamin protects neuronal cell death through inhibition of microglial activation or the production of neurotoxic metabolites and proinflammatory mediators by microglia such as COX-2, iNOS and IL-$1{\beta}$ in global cerebral ischemia.

• Journal of Chest Surgery
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• 제32권5호
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• pp.413-421
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• 1999

배경: 폐장의 허혈-재관류 손상은 폐이식에서 발생하는 조기 이식장기 실패의 주요 원인의 하나로 알려져 있다. 최근 갑상선 호르몬의 활성형인 삼요드티로닌 (T3)이 심장을 비롯한 여러 장기의 허혈 손상을 줄여주는 효과가 있음을 시사하는 보고가 있다. 본 연구에서는 이러한 T3의 허혈-재관류 손상에 대한 효과가 폐장의 허혈 손상에도 효과가 있을 것으로 기대하고 덱스트란을 주성분으로 하는 세포외액성 폐보존액에 T3를 추가한 새로운 폐보존액을 제조하여 그 효과를 검증하고자 하였다. 대상 및 방법: 12마리의 황견을 6마리씩 두 군으로 나누어 제 1군에서는 새로 개발한 폐보존액을 사용하고, 제 2군에서는 유로콜린스 용액을 사용하여 폐를 적출 하였다. 적출한 폐장은 각각의 보존액에 담그어 섭씨 4도에서 20시간 보관한 후, 각 군에 6마리씩 총 12례의 좌측 폐이식을 시행하였다. 이식된 좌측폐만의 기능을 관찰하기 위해서 폐이식 후 재관류를 15분시킨 후에 우측 주폐동맥과 우측 주기관지를 결찰하고, 2시간 동안 혈역학적 변수와 가스분석을 시행하고, 측정이 종료된 후 바로 희생하여 폐조직 일부를 떼어내어 조직검사와 수분 함량 및 MDA양을 측정 비교하였다. 결과: 동맥혈 산소분압은 제 1군에서 재관류 후 60분, 90분 120분에 각각 147$\pm$25 mmHg, 148$\pm$22 mmHg, 159$\pm$21 mmHg, 제 2군에서는 각각 133$\pm$26 mmHg, 132$\pm$29 mmHg, 135$\pm$30 mmHg로 제 1군에서 조금 높은 경향을 보였으나 통계적으로 유의성은 없었다. 각 시간에서의 최대 흡기압은 제 1군에서 14.0$\pm$0.5 cmH2O, 14.2$\pm$0.6 cmH2O, 15.7$\pm$0.8 cmH2O, 제 2군에서는 17.8$\pm$2.0 cmH2O, 18.0$\pm$1.9 cmH2O, 19.3$\pm$2.7 cmH2O으로 제 1군에서 조금 낮은 경향을 보였으나 통계적 유의성은 없었다. 동맥혈 이산화탄소 분압은 제 1군에서 각 시간에 27.9$\pm$2.2 mmHg, 27.7$\pm$2.4 mmHg, 28.0$\pm$3.0 mmHg, 제 2군에서는 36.8$\pm$6.0 mmHg, 43.2$\pm$8.1 mmHg, 53.1$\pm$17.4 mmHg로 제 1군에서 유의하게 낮았다 (p<0.05). 폐혈관 저항 및 조직 MDA양은 두 군간에 유의한 차이가 없었다. 폐 조직 수분 함량은 제 1군에서 유의하게 낮았고, 조직학 검사상 폐조직 손상의 정도도 제 1군에서 적었다. 결론: 이상의 결과에서 T3를 포함한 새로 개발한 폐보존액이 유로콜린스 용액과 비교하여 폐보존능이 우수함을 확인할 수 있었고, 이는 T3가 폐이식시 폐장의 효과적 보존에 유용한 역할을 함을 시사하였다.

• 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.