• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.1-9
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• 2010

AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.

• Journal of Chest Surgery
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• 제34권7호
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• pp.547-551
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• 2001

대동맥궁 재건술시 시행하는 완전순환정지는 술후 신경학적 손상과 관련된다. 저자들은 국소 순환으로 뇌와 심근혈류를 유지하면서 완전순환정지를 시키지 않고 시행한 변형 Norwood술식을 2명에서 시행하였기에 보고한다. 한 명은 체중이 3.1kg인 생후 13일된 여아로서 좌심형성부전증후군의 이형 환자였고 다른 한 명은 생후 38일된 체중 3.4kg의 남아로서 심한 대동맥 발육부전 및 축착증과 좌심실유출로 협착을 동반한 Taussig-Bing 기형이었다. 두 환아 모두 무명동맥에 직접 동맥캐뉼라를 삽관한 다음 저체온 상태에서 무명동맥과 관상동맥 혈류를 유지하면서 Norwood술식을 시행하였으며 두 명 모두 술후 신경학적, 심장 혹은 신기능 합병증은 없었다. 이 방법은 좌심형성부전증후군이나 대동맥 축착증 혹은 단절증과 같은 대동맥궁 기형 환자의 수술시 완전순환정지로 인해 발생될 수 있는 허혈성 손상으로부터 뇌와 심장을 보호할 수 있는 한 방법으로 생각된다.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.19-24
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• 2016

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The exploration of new biomarkers with high sensitivity and specificity for early diagnosis of AMI therefore becomes one of the primary task. In the current study, we aim to detect whether there is any heart specific long noncoding RNA (lncRNA) releasing into the circulation during AMI, and explore its function in the neonatal rat cardiac myocytes injury induced by $H_2O_2$. Our results revealed that the cardiac-specific lncRNA MHRT (Myosin Heavy Chain Associated RNA Transcripts) was significantly elevated in the blood from AMI patients compared with the healthy control ($^*p<0.05$). Using an in vitro neonatal rat cardiac myocytes injury model, we demonstrated that lncRNA MHRT was upregulated in the cardiac myocytes after treatment with hydrogen peroxide ($H_2O_2$) via real-time RT-PCR (qRT-PCR). Furthermore, we knockdowned the MHRT gene by siRNA to confirm its roles in the $H_2O_2$-induced cardiac cell apoptosis, and found that knockdown of MHRT led to significant more apoptotic cells than the non-target control ($^{**}p<0.01$), indicating that the lncRNA MHRT is a protective factor for cardiomyocyte and the plasma concentration of MHRT may serve as a biomarker for myocardial infarction diagnosis in humans AMI.

• Biomolecules & Therapeutics
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• 제9권3호
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• pp.167-175
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• 2001

Recent studies have shown that cytokines are capable of modulating cardiovascular function and that some drugs used in the treatment of heart failure variably modulate the production of cytokines. Hige- namine, a positive inotropic isoquinoline alkaloid, has been used traditionally as cardiac stimulant, and reported to reduce nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression in LPS- and/or cytokine-activated cells in vitro and in vivo. Therefore, we investigated whether higenamine modulates the production of proinflammatory cytokines in myocardial infarction. In addition, effects of higenamine on antioxidant action and antioxidant enzyme expression (MnSOD) were studied. Myocardial infarction (MI) was confirmed by measuring left ventricular (LV) pressure after occlusion of the left anterior descending coronary artery (LAD) for 5 weeks in rats. Treatment of higenamine (10 mg/kg/day) reduced infarct size about 35 %, which accompanied by reduction of production TNF-$\alpha$, IL-6, but not IFN-${\gamma}$ and IL-1$\beta$ in the myocardium. The expression of TNF-$\alpha$ mRNA in infracted myocardium was significantly reduced by higenamine. Although iNOS mRNA was not detected, nitrotyrosine staining was significantly increased in myocardium of Ml compared to higenamine-treated one, Indicating that peroxynitrite-induced damage is evident in MI. Cytochrome c oxidation by peroxynitrite was concentration-dependently reduced by higenamine, an effect which was almost compatible to glutathion. Higenamine treatment did not affect the expression of MnSOD mRNA in myocardial tissues in MI. Taken together, higenamine may be beneficial in oxidative stress conditions such as ischemic-reperfusion injury and MI due to antioxidant action as well as modulation of cytokines.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.147-157
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• 2021

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 ㎛ microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.

• Journal of Ginseng Research
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• 제48권4호
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• pp.395-404
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• 2024

Background: Ginsenoside Rg₁ (Rg₁) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg₁ has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood. Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg₁ against myocardial ischemia (MI) were screened and explored. Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg₁ against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg₁ intervention on H9c2 cells injured by H₂O₂ showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg₁ on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg₁ was also evaluated. Conclusion: Rg₁ can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg₁, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.

• Journal of Chest Surgery
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• 제29권10호
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• pp.1076-1080
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• 1996

허혈후 재관류시 일산화질소의 전구체인 L-arginin에 심근기능에 미치는 영향은 각 연구의 조건에 따라 일정하지 않다. 저자들은 L-arginine의 농도에 의한 심근보호효과의 차이를 알아보고자 본 연구를 시행하였다. 란겐돌프 관류장치하의 흰쥐 적출심장에 37.5$^{\circ}C$에서 30분의 허혈과 30분의 재관류를 실시하면서 재관류시 관류액에 L-arginine을 첨가하여 농도를 1, 2, 3, 4 mm/L로 하였고 대 조군에는 L-arginine을 첨가하지 않았다. 허혈기 직전과 재관류 30분에 좌심실 수축기능(좌심실 발생압, 좌심실압 최대 순간 증가율), 이완기능(좌심실압 최대 순간 감소율)과 관상관류량을 측정하였다. L-arginine 농도가 1mm/L, 2 mm/L인 실험군은 좌심실 발생압, 좌심실압 최대 순간증가율, 좌심실압 최대 순간감소율 및 관상관류량의 회복률이 대조군에 비해 통계적 유의성은 없었으나 우수한 경향을 보였다. 그러나 L-arginine의 농도가 증가함에 따라 회복률은 감소하여 4 mM/L농도의 실험군은 대조군보다 유의하게 낮은 회복률을 보였다(p(0.05). 이러한 연구결과를 통해 심근허혈후 재관류시 심근기능 및 관상관류량 회복을 향상시키기 위해서는 L-arginine을 2mM/ 이하의 농도로 투여 해야 하며 향후 그 이상의 높은 농도에서 나타난 회복 저하에 관한 연구가 필요할 것으로 생각된다.

• 대한방사선기술학회지:방사선기술과학
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• 제24권2호
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• pp.19-22
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• 2001

The purpose of this study is to evaluate time course of signal enhancement on Gadomer-17 enhance MRI, and to correlate the size of enhanced area with that of the infarct area on 2'3'5'-triphenyl tetrazolium chloride(TTC) histochemical examination for the assessment of myocardial viability in reperfused Myocardial Infarction in a cat model. Tan cats(average weight: 3.8 kg) which had undergone 90 minutes of occlusion of the LAD followed by 90 minutes of reperfusion underwent MR T2-weighted imaging, and T1-weighted imaging, enhanced T1-weighted imaging. We used 1.5T Magneton Vision MRI system(Siemens, Erlangen, Germany). Signal intensities were measured in the enhanced and non-enhanced areas of enhanced T1-weighted imaging. and TTC histochemical staining the size of the abnormal signal area on each image was compared with that of the infarct area. Maximum enhancement was detected during a $40{\sim}60$ minute period with an average enhancement of $168{\pm}9.9%$ of normal myocardium. TTC staining revealed that the size of the high signal area on T2-weighted images and of the enhanced area on enhanced T1-weighted images was greater than that of the infarct area($T2=48.1%{\pm}3.7$, enhanced $T1=47.2%{\pm}2.6$, TTC $staining=38.7%{\pm}3.1$ ; p<0.05). In reperfused Myocardial Infarction in a cat model, enhanced MR imaging delineates reversibly and irreversibly damaged myocardium, with a strong enhancement and a broad temporal window. We may therefore expect that enhanced MR image is useful for demonstrating myocardial injury.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.533-543
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• 2021

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

• Clinical and Experimental Pediatrics
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• 제54권2호
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• pp.86-89
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• 2011

Traumatic ventricular septal defect (VSD) resulting from blunt chest injury is a very rare event. The mechanisms of traumatic VSD have been of little concern to dateuntil now, but two dominant theories have been described. In one, the rupture occurs due to acute compression of the heart; in the other, it is due to myocardial infarction of the septum. The clinical symptoms and timing of presentation are variable, so appropriate diagnosis can be difficult or delayed. Closure of traumatic VSD has been based on a combination of heart failure symptoms, hemodynamics, and defect size. Here, we present a case of a 4-year-old boy who presented with a traumatic VSD following a car accident. He showed normal cardiac structure at the time of injury, but after 8 days, his repeated echocardiography revealed a VSD. He was successfully treated by surgical closure of the VSD, and has been doing well up to the present. This report suggests that the clinician should pay great close attention to the patients injured by blunt chest trauma, keeping in mind the possibility of cardiac injury.