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1.
Article in Chinese | WPRIM | ID: wpr-941045

ABSTRACT

OBJECTIVE@#To explore the role of salt-inducible kinase 2 (SIK2) in myocardial ischemia-reperfusion (IR) injury in rats.@*METHODS@#Fifteen male SD rats were randomized equally into sham operation group, myocardial IR model group, and SIK2 inhibitor group (in which the rats were treated with intravenous injection of 10 mg/kg bosutinib via the left femoral vein 24 h before modeling). Ultrasound was used to detect the cardiac function of the rats, and myocardial pathologies were observed with HE staining. Transmission electron microscopy was used to observe autophagy of myocardial cells, and Western blotting was performed to detect the contents of the autophagy-related proteins SIK2, LC3B, Beclin-1, p62 and the expressions of p-mTOR, mTOR, p-ULK1, and ULK1 in myocardial tissue.@*RESULTS@#Myocardial IR injury significantly increased the number of autophagosomes (P < 0.05) and the expression of SIK2 protein (P < 0.01) in the myocardial tissues. Treatment with bosutinib before modeling obviously lowered the expression of SIK2 protein (P < 0.01), alleviated myocardial pathologies, and reduced the number of autophagosomes (P < 0.05) in the myocardial tissue. The rats with myocardial IR injury showed obviously lowered LVEF and FS values (P < 0.001), which were significantly improved by bosutinib treatment (P < 0.05); no significant difference was detected in IVSDd or LVPWDd among the 3 groups (P > 0.05). Myocardial IR injury obviously increased the expressions of LC3-II/LC3-I and Beclin-1 proteins and lowered the expression of p62 protein (P < 0.01), and these changes were significantly rescued by bosutinib treatment (P < 0.05). The rat models of myocardial IR injury showed significantly increased expression of p-ULK1 (Ser757) (P < 0.01) and lowered expression of p-mTOR protein (P < 0.0001) in the myocardium, and these changes were obviously reversed by bosutinib (P < 0.01 or 0.05); there was no significant difference in mTOR and ULK1 expressions among the 3 groups (P > 0.05).@*CONCLUSION@#SIK2 may promote autophagy through the mTOR/ULK1 signaling pathway, and inhibiting SIK2 can reduce abnormal autophagy and alleviate myocardial IR injury in rats.


Subject(s)
Animals , Autophagy , Autophagy-Related Protein-1 Homolog/metabolism , Beclin-1/metabolism , Down-Regulation , Male , Myocardial Reperfusion Injury , Protein Serine-Threonine Kinases , Rats , Rats, Sprague-Dawley , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
2.
Arq. bras. cardiol ; 117(6): 1134-1144, dez. 2021. graf
Article in Portuguese | LILACS | ID: biblio-1350046

ABSTRACT

Resumo Fundamento A cardiopatia isquêmica atraiu muito atenção devido às altas taxas de mortalidade, custos do tratamento e a crescente morbidade na população jovem. Estratégias de reperfusão reduziram a mortalidade. Porém, a reperfusão pode levar à morte do cardiomiócito e subsequente dano irreversível ao miocárdio. No momento, não há um tratamento eficiente e direcionado para a lesão de isquemia-reperfusão (I/R). Objetivos Avaliar se a dexmedetomidina (DEX) tem efeito protetivo na I/R do miocárdio e explorar os possíveis mecanismos por trás dela. Métodos Corações de ratos foram perfundidos com o sistema de perfusão de Langendorff e aleatoriamente distribuídos em cinco grupos: grupo controle, perfundido com solução de Krebs-Henseleit (K-H) por 205 minutos sem isquemia; e quatro grupos de teste que foram submetidos a 40 minutos de isquemia global e 120 minutos de reperfusão. O Grupo DEX, o grupo ioimbina (IO) e o grupo DEX + IO foram perfundidos com DEX (10 nM), IO (1 μM) ou a combinação de DEX e IO antes da reperfusão, respectivamente. A hemodinâmica cardíaca, o tamanho do infarto do miocárdio e a histologia do miocárdio foram avaliados. A expressão da proteína-78 regulada pela glicose (GRP78), a proteína quinase do retículo endoplasmático (PERK), a PERK fosforilada, o fator de iniciação eucariótico 2α (eIF2α), eIF2α fosforilado, o fator de transcrição 4 (TCF-4) e a proteína homóloga à proteína ligadora do acentuador CCAAT (CHOP) foram avaliados. P< 0,05 foi considerado para indicar a diferença estatisticamente significativa. Resultados O pré-condicionamento com DEX melhorou a função cardíaca nos corações com I/R, reduziu o infarto do miocárdio, a apoptose do miocárdio e a expressão de GRP78, p-PERK, eIF2α, p-eIF2α, TCF-4 e CHOP. Conclusões O pré-tratamento com DEX reduziu a lesão de I/R no miocárdio ao suprimir a apoptose, o que foi induzido pela via PERK.


Abstract Background Ischemic heart disease has attracted much attention due to its high mortality rates, treatment costs and the increasing morbidity in the young population. Strategies for reperfusion have reduced mortality. However, reperfusion can lead to cardiomyocyte death and subsequent irreversible myocardial damage. At present, the timely and targeted treatment of ischemia-reperfusion (I/R) injury is often lacking. Objectives To evaluate if dexmedetomidine (DEX) has a protective effect in myocardiual I/R and explore the possible mechanism behind it. Methods Rat hearts were perfused with a Langendorff perfusion system, and randomly assigned to five groups: control group, perfused with Krebs-Henseleit (K-H) solution for 205 minutes without ischemia; and four test groups that underwent 40 minutes of global ischemia and 120 min of reperfusion. The DEX group, the yohimbine (YOH) group and the DEX + YOH group were perfused with DEX (10 nM), YOH (1 μM) or the combination of DEX and YOH prior to reperfusion, respectively. Cardiac hemodynamics, myocardial infarct size, and myocardial histology were evaluated. The expression of glucose-related protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phosphorylated PERK, eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α, activating transcription factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) were assessed. P<0.05 was considered to indicate a statistically significant difference. Results DEX preconditioning improved the cardiac function of I/R hearts, reduced myocardial infarction, myocardial apoptosis, and the expression of GRP78, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. Conclusions DEX pretreatment reduced myocardial I/R injury by suppressing apoptosis, which was induced by the PERK pathway.


Subject(s)
Animals , Rats , Myocardial Reperfusion Injury/prevention & control , Reperfusion Injury , Myocardial Ischemia , Dexmedetomidine/pharmacology , Myocardial Infarction/prevention & control , Myocardial Infarction/drug therapy , Signal Transduction
4.
Article in Chinese | WPRIM | ID: wpr-877651

ABSTRACT

OBJECTIVE@#To observe the effect of electroacupuncture (EA) preconditioning at heart meridian acupoints on the contents of dopamine (DA) and 5-hydroxytryptamine (5-HT) in lateral hypothalamus area (LHA) and cerebellar fastigial nucleus (FN) in the rats with acute myocardial ischemia-reperfusion injury (MIRI), and explore the role and mechanism of LHA and FN in the effect of EA at heart meridian acupoints against acute MIRI.@*METHODS@#Sixty SD rats were randomly divided into a sham-operation group, a model group, an EA heart meridian group and an EA lung meridian group, 12 rats in each group, as well as an LHA plus heart meridian group (damage of bilateral LHA) and an FN plus heart meridian group (damage of bilateral FN), 6 rats in each one. Three days after nucleus destruction, EA was applied to "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA heart meridian group, the LHA plus heart meridian group and the FN plus heart meridian group and EA was applied to "Taiyuan" (LU 9) and "Lieque" (LU 7) in the EA lung meridian group, with 1 V in stimulating voltage and 2 Hz in frequency, lasting 20 minutes each time, once a day, for consecutively 7 days before model replication. Except in the sham-operation group, MIRI rat models were duplicated by ligation of the left anterior descending branch of the coronary artery in the rest groups. Using Power lab physiological recorder, ST segment displacement value was recorded before modeling, 30 min after ligation and 120 min after reperfusion separately. The high performance liquid chromatography-electrochemical detection and analysis system was adopted to determine the contents of DA and 5-HT in LHA and FN dialysate after rat modeling in each group.@*RESULTS@#In comparison of ST segment displacement value 30 min after ligation and 120 min after reperfusion among groups, the value in the model group was higher than that in the sham-operation group (@*CONCLUSION@#EA preconditioning at heart meridian acupoints can effectively alleviate myocardial injury in acute MIRI rats, during which, DA and 5-HT in LHA and FN may be the important material basis.


Subject(s)
Acupuncture Points , Animals , Cerebellar Nuclei , Dopamine , Electroacupuncture , Hypothalamic Area, Lateral , Myocardial Ischemia , Myocardial Reperfusion Injury/therapy , Rats , Rats, Sprague-Dawley , Serotonin
5.
Article in Chinese | WPRIM | ID: wpr-922023

ABSTRACT

OBJECTIVE@#To study the effect of down-regulating miR-488 targeting Jag1 on the injury of hypoxia-reoxygenation myocardial H9c2 cells.@*METHODS@#A hypoxic-reoxygenated myocardial H9c2 cell injury model was constructed. miR-488 inhibitor was used to transfect the cells. CCK-8 method and flow cytometry were used to detect cell proliferation and apoptosis in each group. Lactate dehydrogenase (LDH), superoxide dismutase (SOD), malonaldehyde (MDA), catalase (CAT) levels were detected. Western blotting was used to detect the expression of Bcl-2 associated X Protein (Bax) and B cell lymphoma/lewkmia-2 (Bcl-2). Target genes of miR-488 were predicted, and a luciferase reporter system was used to verify the targeting relationship between the two. Myocardial H9c2 cells were co-transfected with miR-488 inhibitor and Jag1 siRNA, and treated with hypoxia and reoxygenation, cell proliferation, apoptosis, LDH, SOD, MDA, CAT levels, and Bax, Bcl-2 protein expression were detected.@*RESULTS@#The expression of miR-488 in the hypoxia-reoxygenated myocardial H9c2 cells was increased, along with reduced cell proliferation, increased apoptosis, increased Bax protein expression, decreased Bcl-2 protein expression, increased MDA, decreased CAT and SOD, and increased LDH level in the supernatant of cell culture. When myocardial H9c2 cells were transfected with miR-488 inhibitor and treated with hypoxia and reoxygenation, the expression of miR-488 was decreased, along with increased cell proliferation, decreased apoptosis, decreased Bax protein expression, increased Bcl-2 protein expression, decreased MDA, increased CAT and SOD, and decreased LDH level in the supernatant of cell culture. Down-regulation of miR-488 could target and down-regulate Jag1 expression. And Jag1 siRNA could reverse the effect of miR-488 inhibitor on the proliferation, apoptosis, LDH, SOD, MDA, CAT levels and the expression of Bax and Bcl-2 of hypoxic-reoxygenated myocardial H9c2 cells.@*CONCLUSION@#Down-regulating miR-488 targeted Jag1 can attenuate hypoxia-reoxygenation induced myocardial H9c2 cell injury.


Subject(s)
Apoptosis/genetics , Down-Regulation , Humans , Hypoxia/genetics , Jagged-1 Protein/genetics , MicroRNAs/genetics , Myocardial Reperfusion Injury , Myocytes, Cardiac
6.
Article in Chinese | WPRIM | ID: wpr-888403

ABSTRACT

OBJECTIVE@#To study the effect of silencing LncRNA SNHG7 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its targeted regulation on miR-181b-5p.@*METHODS@#Rat cardiomyocytes H9c2 were cultured in vitro and randomly divided into control group, H/R group, H/R + si-NC group, H/R + si-SNHG7 group, H/R + si-SNHG7 + anti-miR-NC group and H/R + si-SNHG7 + anti-miR-181b-5p group. The content of lactate dehydrogenase (LDH), malondialedhyde (MDA) and the activity of superoxide dismutase (SOD) were detected. Flow cytometry was carried out to detect the rate of apoptosis. qRT-PCR was used to detect the expression of SNHG7 and miR-181b-5p. Dual luciferase report experiment was used to verify the targeting relationship between SNHG7 and miR-181b-5p. Western blotting was used to detect the expression of Bax and Bcl-2.@*RESULTS@#Compared with the control group, the H/R group showed significantly increased SNHG7 expression in cardiomyocytes, reduced miR-181b-5p expression, higher levels of LDH and MDA, reduced activity of SOD, increased cell apoptosis rate, higher level of Bax protein, and reduced level of Bcl-2 protein (all P< 0.05). Compared with the H/R and H/R + si-NC groups, the H/R + si-SNHG7 group had significantly reduced level of LDH and MDA, increased activity of SOD, reduced apoptosis rate, reduced level of Bax protein, increased level of Bcl-2 protein (all P< 0.05). The dual luciferase report experiment confirmed that SNHG7 could target miR-181b-5p. Interference with the expression of miR-181b-5p could reduce the effect of silencing SNHG7 on H/R-induced cardiomyocyte oxidative stress and apoptosis.@*CONCLUSION@#Silencing SNHG7 may inhibit H/R-induced cardiomyocyte oxidative stress and apoptosis by up-regulating the expression of miR-181b-5p, thereby exerting a protective effect on cardiomyocytes.


Subject(s)
Animals , Apoptosis , Hypoxia , MicroRNAs/genetics , Myocardial Reperfusion Injury , Myocytes, Cardiac , RNA, Long Noncoding/genetics , Rats
7.
Article in Chinese | WPRIM | ID: wpr-888120

ABSTRACT

The study aims to investigate the effect of the compatibility of paeonol and paeoniflorin(hereinafter referred to as the compatibility) on the expression of myocardial proteins in rats with myocardial ischemia injury and explore the underlying mechanism of the compatibility against myocardial ischemia injury. First, the acute myocardial infarction rat model was established by ligation of the anterior descending branch of the left coronary artery. The model rats were given(ig) paeonol and paeoniflorin. Then protein samples were collected from rat cardiac tissue and quantified by tandem mass tags(TMT) to explore the differential proteins after drug intervention. The experimental results showed that differential proteins mainly involved phagocytosis engulfment, extracellular space, and antigen binding, as well as Kyoto encyclopedia of genes and genomes(KEGG) pathways of complement and coagulation cascades, syste-mic lupus erythematosus, and ribosome. In this study, the target proteins and related signaling pathways identified by differential proteomics may be the biological basis of the compatibility against myocardial ischemia injury in rats.


Subject(s)
Acetophenones , Animals , Glucosides , Monoterpenes , Myocardial Ischemia/genetics , Myocardial Reperfusion Injury , Proteomics , Rats , Rats, Sprague-Dawley
8.
Article in Chinese | WPRIM | ID: wpr-879038

ABSTRACT

Myocardial ischemia-reperfusion injury(MIRI) is an urgent problem in clinical treatment. As cardiomyocytes are terminal cells, MIRI-induced cardiomyocyte death will irreversibly damage the structure and function of the heart. In previous studies, apoptosis was considered to be the only way to regulate cell death, while necrosis could not be regulated. However, current studies have shown that cell necrosis could also be regulated, which was collectively called programmed cell death(PCD). Regulated cell death is actively mediated through molecular pathways, so there is the possibility of inhibiting this signaling to reduce MIRI. At present, PCD mainly includes apoptosis, autophagy, necrosis, pyroptosis and ferroptosis. As a unique treature in China, traditional Chinese medicine has the advantages of multiple pathways, multiple targets, low toxicity, less side effects and low economic costs. With the in-depth study of the efficacy of traditional Chinese medicine against MIRI, it has been confirmed that traditional Chinese medicine could regulate PCD to reduce MIRI. Therefore, this paper focuses on the relationship between PCD and MIRI, and new studies on intervention with relevant traditional Chinese medicine, with the aim to provide new MIRI prevention and treatment methods from the perspective of "intervention of PCD".


Subject(s)
Apoptosis , China , Humans , Medicine, Chinese Traditional , Myocardial Reperfusion Injury/genetics , Myocytes, Cardiac
9.
Acta cir. bras ; 36(2): e360207, 2021. tab, graf
Article in English | LILACS | ID: biblio-1152700

ABSTRACT

ABSTRACT Purpose The present study explored the influence of liraglutide on remote preconditioning-mediated cardioprotection in diabetes mellitus along with the role of nuclear factor erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor (HIF-1α) and hydrogen sulfide (H2S). Methods Streptozotocin was given to rats to induce diabetes mellitus and rats were kept for eight weeks. Four cycles of ischemia and reperfusion were given to hind limb to induce remote preconditioning. After 24 h, hearts were isolated and subjected to 30 min of ischemia and 120 min of reperfusion on Langendorff system. Liraglutide was administered along with remote preconditioning. Cardiac injury was assessed by measuring the release of creatine kinase (CK-MB), cardiac troponin (cTnT) and development of left ventricular developed pressure. After ischemia-reperfusion, hearts were homogenized to measure the nuclear cytoplasmic ratio of Nrf2, H2S and HIF-1α levels. Results In diabetic rats, there was more pronounced injury and the cardioprotective effects of remote preconditioning were not observed. Administration of liraglutide restored the cardioprotective effects of remote preconditioning in a dose-dependent manner. Moreover, liraglutide increased the Nrf2, H2S and HIF-1α levels in remote preconditioning-subjected diabetic rats. Conclusions Liraglutide restores the lost cardioprotective effects of remote preconditioning in diabetes by increasing the expression of Nrf2, H2S and HIF-1α.


Subject(s)
Animals , Rats , Myocardial Reperfusion Injury/prevention & control , Ischemic Preconditioning, Myocardial , Diabetes Mellitus, Experimental/drug therapy , Hydrogen Sulfide , Hydrogen Sulfide/pharmacology , Myocardial Infarction , Signal Transduction , Rats, Wistar , NF-E2-Related Factor 2 , Liraglutide/pharmacology
10.
CorSalud ; 12(2): 214-218,
Article in Spanish | LILACS | ID: biblio-1133612

ABSTRACT

RESUMEN La N-acetilcisteína es conocida en varias especialidades médicas. Su empleo en cardiología se ha incrementado desde hace décadas, por su potencial para disminuir el impacto del daño por reperfusión en el infarto miocárdico agudo. Pero el espectro de sus efectos es aún mayor, tiene acciones sobre los radicales de oxígeno, con un papel protector, por la vía de los grupos sulfhidrilos de regiones importantes de la membrana celular, los cuales interfieren y tienen efecto en la función endotelial y en los procesos complejos de adhesión como efectos secundarios; así como otros fenómenos del compartimento extravascular. Estos procesos están estrechamente relacionados con el aparato cardiovascular.


ABSTRACT N-acetylcysteine is known in a number of medical specialties and its ability to decrease the impact of reperfusion injury in acute myocardial infarction has boosted its use in cardiology over the past decades. N-acetylcysteine has a far-reaching range of effects since it functions as a protective agent against oxygen radicals through sulfhydryl groups in important regions of the cell membrane that interfere and affect endothelial functioning and complex adhesion processes as side effects; as well as other phenomena of the extravascular compartment. These processes are closely related to the cardiovascular system.


Subject(s)
Acetylcysteine , Myocardial Reperfusion Injury , Reperfusion Injury , Oxidative Stress
11.
CorSalud ; 12(2): 171-183, graf
Article in Spanish | LILACS | ID: biblio-1133607

ABSTRACT

RESUMEN Desde los primeros informes de pacientes infectados con el SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) en la provincia China de Wuhan, la infección por el nuevo coronavirus ha contagiado a más de 4,7 millones de personas y los fallecidos superan los 315000, hasta el 18 de mayo del 2020. La lesión o daño miocárdico queda definido, como la detección de un valor de las troponinas cardíacas (T o I) por encima del percentil 99 del límite superior de referencia. El mecanismo exacto a partir del cual esta infección por el nuevo coronavirus le infringe un daño a las células del corazón no ha quedado totalmente esclarecido; no obstante, numerosos podrían ser los factores a tener en cuenta: desequilibrio entre el aporte y la demanda, la respuesta inflamatoria sistémica, hipoxia, disfunción microvascular y el daño miocárdico directo ocasionado por el virus.


ABSTRACT Since the first reports of patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) appeared in the Chinese province of Wuhan, the infection by the new coronavirus has infected more than 4.7 millions of people, and the amount of deaths is greater than 315,000, until May 18, 2020. The myocardial injury or damage is defined as the detection of a value of cardiac troponins (T or I) above the 99th percentile of the upper reference limit. The exact mechanism, from which this infection by the new coronavirus causes damage to the heart cells, has not been completely clarified; however, numerous factors could be taken into account: imbalance between the supply and the demand, systemic inflammatory response, hypoxia, microvascular dysfunction and the direct myocardial injury caused by the virus.


Subject(s)
Myocardial Reperfusion Injury , Coronavirus Infections , Peptidyl-Dipeptidase A
12.
Rev. colomb. cardiol ; 27(3): 142-152, May-June 2020. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1289204

ABSTRACT

Resumen La infección por SARS-CoV2 es una pandemia. Se creía que el primer caso de esta enfermedad ocurrió el 8 de diciembre de 2019 en la provincia de Hubei en China, aunque posteriormente se indicó que el primer caso confirmado por laboratorio ocurrió el 1.( de diciembre de 2019 ante la presencia de un brote de neumonía en 59 pacientes sospechosos en un mercado local de mariscos en Wuhan. No solo produce patología respiratoria, con frecuencia compremete el sistema cardiovascular ya que produce lesión miocárdica, miocarditis, y, con cierta frecuencia, aumenta la descompensación de enfermedades cardiovasculares preestablecidas. En este artículo se trata de dilucidar el componente cardiovascular hasta ahora existente en la literatura y se sugieren algunos pasos a seguir en pacientes con estas enfermedades, acorde con la evidencia actual.


Abstract Infection due to SARS-CoV2 is a pandemic. It is believed that the first case occurred on 8 December 2019 in Hubei province in China, although it was later indicated that the first laboratory-confirmed case occurred on 1 December 2019 due to the presence of an outbreak of suspected pneumonia in 59 patients in a shellfish market in Wuhan. It not only caused a respiratory disease, it often compromised the cardiovascular system since it produces a myocardial lesion, myocarditis, and, less often, increased the decompensation of pre-established cardiovascular diseases. An attempt is made in this article to elucidate the cardiovascular component presented in the current literature, and to suggest some steps to follow in patients with these diseases in accordance with the current evidence.


Subject(s)
Humans , Male , Female , Coronavirus , Heart Failure , Pneumonia , Respiratory Distress Syndrome, Newborn , Myocardial Reperfusion Injury , Severe Acute Respiratory Syndrome , Myocarditis
13.
Arq. bras. cardiol ; 114(1): 78-86, Jan. 2020. tab, graf
Article in English | LILACS | ID: biblio-1055096

ABSTRACT

Abstract Background: Euterpe oleracea Mart. (açaí) is a fruit with high antioxidant capacity and could be an adjuvant strategy to attenuate ischemia-reperfusion injury. Objective: To evaluate the influence of açaí in global ischemia-reperfusion model in rats. Methods: Wistar rats were assigned to 2 groups: Control (C: receiving standard chow; n = 9) and Açaí (A: receiving standard chow supplemented with 5% açaí; n = 10). After six weeks, the animals were subjected to the global ischemia-reperfusion protocol and an isolated heart study to evaluate left ventricular function. Level of significance adopted: 5%. Results: There was no difference between the groups in initial body weight, final body weight and daily feed intake. Group A presented lower lipid hydroperoxide myocardial concentration and higher catalase activity, superoxide dismutase and glutathione peroxidase than group C. We also observed increased myocardial activity of b-hydroxyacyl coenzyme-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase in the A group as well as lower activity of the lactate dehydrogenase and phosphofructokinase enzymes. The systolic function was similar between the groups, and the A group presented poorer diastolic function than the C group. We did not observe any difference between the groups in relation to myocardial infarction area, total and phosphorylated NF-kB, total and acetylated FOXO1, SIRT1 and Nrf-2 protein expression. Conclusion: despite improving energy metabolism and attenuating oxidative stress, açai supplementation did not decrease the infarcted area or improve left ventricular function in the global ischemia-reperfusion model.


Resumo Fundamento: Euterpe oleracea Mart. (açaí) é uma fruta com alta capacidade antioxidante e pode ser uma estratégia adjuvante para atenuar a lesão de isquemia-reperfusão. Objetivo: Avaliar a influência do açaí no modelo global de isquemia-reperfusão em ratos. Metodologia: Ratos Wistar foram divididos em 2 grupos: Controle (C: recebendo ração padrão; n = 9) e Açaí (A: recebendo ração padrão suplementada com 5% de açaí; n = 10). Após seis semanas, os animais foram submetidos ao protocolo global de isquemia-reperfusão e a estudo do coração isolado para avaliar a função ventricular esquerda. Nível de significância adotado: 5%. Resultados: Não houve diferença entre os grupos quanto ao peso corporal inicial e final, e a ingestão diária de ração. O grupo A apresentou menor concentração miocárdica de hidroperóxido lipídico e maior atividade de catalase, superóxido dismutase e glutationa peroxidase do que o grupo C. Também observamos aumento da atividade miocárdica da b-hidroxiacil coenzima-A desidrogenase, piruvato desidrogenase, citrato sintase, complexo I, complexo II e ATP sintase no grupo A, bem como menor atividade das enzimas lactato desidrogenase e fosfofructoquinase. A função sistólica foi semelhante entre os grupos, e o grupo A apresentou função diastólica pior que C. Não foram observadas diferenças entre os grupos em relação à área de infarto do miocárdio, e expressão proteica de NF-kB total e fosforilado, e das proteínas FOXO1, SIRT1 e Nrf-2. Conclusão: apesar de melhorar o metabolismo energético e atenuar o estresse oxidativo, a suplementação de açaí não diminuiu a área infartada nem melhorou a função ventricular esquerda no modelo global de isquemia-reperfusão.


Subject(s)
Animals , Male , Rats , Plant Extracts/pharmacology , Myocardial Reperfusion Injury/physiopathology , Oxidative Stress/drug effects , Energy Metabolism/drug effects , Euterpe/chemistry , Oxidative Stress/physiology , Disease Models, Animal , Energy Metabolism/physiology
15.
Braz. j. med. biol. res ; 53(9): 0-0, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132553

ABSTRACT

Myocardial ischemia/reperfusion (MI/R) injury is a complex phenomenon that causes severe damage to the myocardium. However, the potential molecular mechanisms of MI/R injury have not been fully clarified. We identified potential molecular mechanisms and therapeutic targets in MI/R injury through analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were found between MI/R injury and normal samples, and overlapping DEGs were found between GSE61592 and GSE67308. Gene Ontology (GO) and pathway analysis were performed for overlapping DEGs by Database for Annotation, Visualization and Integration Discovery (DAVID). Then, a network of protein-protein interaction (PPI) was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) database. Potential microRNAs (miRNAs) and therapeutic small molecules were screened out using microRNA.org database and the Comparative Toxicogenomics database (CTD), respectively. Finally, we identified 21 overlapping DEGs related to MI/R injury. These DEGs were significantly enriched in IL-17 signaling pathway, cytosolic DNA-sensing pathway, chemokine signaling, and cytokine-cytokine receptor interaction pathway. According to the degree in the PPI network, CCL2, LCN2, HP, CCL7, HMOX1, CCL4, and S100A8 were found to be hub genes. Furthermore, we identified potential miRNAs (miR-24-3p, miR-26b-5p, miR-2861, miR-217, miR-4251, and miR-124-3p) and therapeutic small molecules like ozone, troglitazone, rosiglitazone, and n-3 polyunsaturated fatty acids for MI/R injury. These results identified hub genes and potential small molecule drugs, which could contribute to the understanding of molecular mechanisms and treatment for MI/R injury.


Subject(s)
Myocardial Reperfusion Injury , MicroRNAs , Computational Biology , Gene Expression Profiling , Gene Regulatory Networks , Protein Interaction Maps , Gene Ontology
16.
Article in Chinese | WPRIM | ID: wpr-828936

ABSTRACT

OBJECTIVE@#To investigate the protective effect of melatonin against myocardial ischemia reperfusion (IR) injury in isolated rat hearts and explore the underlying mechanisms.@*METHODS@#The isolated hearts from 40 male SD rats were randomly divided into 4 groups (=10): the control group, where the hearts were perfused with KH solution for 175 min; IR group, where the hearts were subjected to global ischemia for 45 min followed by reperfusion for 120 min; IR+melatonin (Mel+IR) group, where melatonin (5 μmol/L) was administered to the hearts 1 min before ischemia and during the first 5 min of reperfusion, followed by 115 min of reperfusion; and IR+2, 3-butanedione monoxime (IR+BDM) group, where the hearts were treated with BDM (20 mmol/L) in the same manner as melatonin treatment. Myocardial injury in the isolated hearts was assessed based on myocardial injury area, caspase-3 activity, and expressions of cytochrome C and cleaved caspase-3 proteins. Cardiac contracture was assessed using HE staining and by detecting lactate dehydrogenase (LDH) activity and the content of cardiac troponin I (cTnI) in the coronary outflow, measurement of left ventricular end-diastolic pressure (LVEDP) and electron microscopy. The content of ATP in the cardiac tissue was also determined.@*RESULTS@#Compared with those in the control group, the isolated hearts in IR group showed significantly larger myocardial injury area and higher caspase-3 activity and the protein expressions of cytochrome C and cleaved caspase-3 with significantly increased LDH activity and cTnI content in the coronary outflow and elevated LVEDP at the end of reperfusion; HE staining showed obvious fractures of the myocardial fibers and the content of ATP was significantly decreased in the cardiac tissue; electron microscopy revealed the development of contraction bands. In the isolated hearts with IR, treatment with Mel or BDM significantly reduced the myocardial injury area, caspase-3 activity, and protein expressions of cytochrome C and cleaved caspase-3, obviously inhibited LDH activity, lowered the content of cTnI and LVEDP, reduced myocardial fiber fracture, and increased ATP content in the cardiac tissue. Both Mel and BDM inhibited the formation of contraction bands in the isolated hearts with IR injury.@*CONCLUSIONS@#Mel can alleviate myocardial IR injury in isolated rat hearts by inhibiting cardiac contracture, the mechanism of which may involve the upregulation of ATP in the cardiac myocytes to lessen the tear of membrane and reduce cell content leakage.


Subject(s)
Animals , Contracture , Male , Melatonin , Myocardial Ischemia , Myocardial Reperfusion Injury , Myocardium , Myocytes, Cardiac , Rats , Rats, Sprague-Dawley
17.
Article in Chinese | WPRIM | ID: wpr-828880

ABSTRACT

OBJECTIVE@#To investigate the mechanism by which dripping pills (STDP) improves coronary microcirculation disorder (CMD) and cardiac dysfunction in a porcine model of myocardial ischemia-reperfusion injury.@*METHODS@#Fourteen minipigs were randomly selected for interventional balloon occlusion of the middle left anterior descending branch to induce CMD, and another 7 pigs received sham operation. The pig models of CMD were randomized equally into the model group and STDP-treated group. All the animals were fed with common feed for 8 weeks, and in STDP-treated group, the pigs were given STDP at the daily dose of 3 mg/kg (mixed with feed) for 8 weeks. Before and at the 8th week after the operation, the pigs underwent coronary angiography and echocardiography to determine the vessel lumen diameter and TIMI frame count (CTFC). The pathologies of the myocardium and the microvessels were examined with HE staining at the 8th week. Western blotting was used to detect the expression of silencing information regulator (Sirt1), peroxidase proliferator-activated receptor-γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), extracellular signal-regulated kinase1/2 (ERKI/2), Toll-like receptor 4 (TLR4), and uncoupling protein 2 (UCP2) in myocardial tissue.@*RESULTS@#Before and at the 8th week after the operation, the diameter of the anterior descending vessel in the 3 groups did not differ significantly ( > 0.05). At the 8th week, the number of CTFC frames in the model group increased significantly compared with that in the sham-operated group, but was obviously lowered by treatment with STDP ( < 0.05). Myocardial ischemia-reperfusion injury significantly increased the interventricular septal thickness at end-diastole, left ventricular end-diastole dimension, end-diastole volume, interventricular septal thickness at end-systole and left ventricular mass at 8 weeks after the modeling ( < 0.05), but such changes were significantly alleviated by treatment with STDP (P < 0.05). STDP treatment markedly alleviated myocardial microvascular congestion, thrombosis and peripheral inflammatory cell infiltration induced by myocardial ischemia-reperfusion, but atrophy of the myocardial muscle fiber remained distinct. STDP obviously suppressed the down-regulation of Sirt1, PGC-1α, and PPARα and the up-regulation of ERK1/ 2, TLR4, and UCP2 in the myocardial tissues induced by myocardial ischemia-reperfusion injury.@*CONCLUSIONS@#STDP has anti-inflammatory effects and regulates energy metabolism in the myocardium through modulating Sirt1, PGC-1α, PPARα, ERKI/2, TLR4, and UCP2 to improve CMD and cardiac dysfunction after myocardial ischemia-reperfusion.


Subject(s)
Animals , Drugs, Chinese Herbal , Microcirculation , Myocardial Reperfusion Injury , Myocardium , Rats , Rats, Sprague-Dawley , Swine
18.
Article in Chinese | WPRIM | ID: wpr-828517

ABSTRACT

OBJECTIVE@#To investigate the protective effect of melatonin against myocardial ischemia reperfusion (IR) injury in isolated rat hearts and explore the underlying mechanisms.@*METHODS@#The isolated hearts from 40 male SD rats were randomly divided into 4 groups (=10): the control group, where the hearts were perfused with KH solution for 175 min; IR group, where the hearts were subjected to global ischemia for 45 min followed by reperfusion for 120 min; IR+melatonin (Mel+IR) group, where melatonin (5 μmol/L) was administered to the hearts 1 min before ischemia and during the first 5 min of reperfusion, followed by 115 min of reperfusion; and IR+2, 3-butanedione monoxime (IR+BDM) group, where the hearts were treated with BDM (20 mmol/L) in the same manner as melatonin treatment. Myocardial injury in the isolated hearts was assessed based on myocardial injury area, caspase-3 activity, and expressions of cytochrome C and cleaved caspase-3 proteins. Cardiac contracture was assessed using HE staining and by detecting lactate dehydrogenase (LDH) activity and the content of cardiac troponin I (cTnI) in the coronary outflow, measurement of left ventricular end-diastolic pressure (LVEDP) and electron microscopy. The content of ATP in the cardiac tissue was also determined.@*RESULTS@#Compared with those in the control group, the isolated hearts in IR group showed significantly larger myocardial injury area and higher caspase-3 activity and the protein expressions of cytochrome C and cleaved caspase-3 with significantly increased LDH activity and cTnI content in the coronary outflow and elevated LVEDP at the end of reperfusion; HE staining showed obvious fractures of the myocardial fibers and the content of ATP was significantly decreased in the cardiac tissue; electron microscopy revealed the development of contraction bands. In the isolated hearts with IR, treatment with Mel or BDM significantly reduced the myocardial injury area, caspase-3 activity, and protein expressions of cytochrome C and cleaved caspase-3, obviously inhibited LDH activity, lowered the content of cTnI and LVEDP, reduced myocardial fiber fracture, and increased ATP content in the cardiac tissue. Both Mel and BDM inhibited the formation of contraction bands in the isolated hearts with IR injury.@*CONCLUSIONS@#Mel can alleviate myocardial IR injury in isolated rat hearts by inhibiting cardiac contracture, the mechanism of which may involve the upregulation of ATP in the cardiac myocytes to lessen the tear of membrane and reduce cell content leakage.


Subject(s)
Animals , Heart , Male , Melatonin , Pharmacology , Therapeutic Uses , Muscle Contraction , Myocardial Reperfusion Injury , Drug Therapy , Myocytes, Cardiac , Rats , Rats, Sprague-Dawley
19.
Acta Physiologica Sinica ; (6): 433-440, 2020.
Article in Chinese | WPRIM | ID: wpr-827044

ABSTRACT

The aim of the present study was to investigate the effect of zinc transporter Zip2 (SLC39A2) on mitochondrial respiration during myocardial ischemia/reperfusion (I/R) and the underlying mechanisms. An in vivo myocardial I/R model was established in mice by ligation of left anterior descending coronary artery. Cardiac zinc concentration was measured by inductively coupled plasma-optical emission spectrometer (ICP-OES), and the mitochondrial respiratory function and oxidative phosphorylation were determined by high-resolution respirometry (Oxygraph-2K). The phosphorylation levels of STAT3 and ERK in myocardial tissue were detected by Western blot. The results showed that, compared with the sham group, cardiac zinc concentration in myocardium was decreased in wild-type mice and further reduced in Zip2 knockout mice after I/R. Mitochondrial respiratory control rate (RCR) and oxidative phosphorylation were decreased in Zip2 knockout mice and worsened by I/R. Phosphorylation levels of STAT3 (Ser) and ERK were significantly decreased in Zip2 knockout mice after I/R. In I/R myocardial tissue, STAT3 overexpression significantly improved the mitochondrial respiratory function, while STAT3 dominant negative mutant (STAT3 S727A) inhibited mitochondrial respiratory function. Moreover, the impairment of mitochondrial function by Zip2 knockout was reversed by STAT3 overexpression. These results suggest that Zip2 regulates mitochondrial respiration via phosphorylation of STAT3 during myocardial I/R, which may represent the underlying mechanism of Zip2 cardioprotection against I/R injury.


Subject(s)
Animals , Carrier Proteins , Mice , Mice, Knockout , Mitochondria , Myocardial Reperfusion Injury , Myocardium , Myocytes, Cardiac
20.
Article in Chinese | WPRIM | ID: wpr-880763

ABSTRACT

OBJECTIVE@#To investigate the effect of miR-133b on cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion (I/R) and explore the mechanism.@*METHODS@#Thirty-six adult SD rats were randomized into sham-operated group, I/R group, AdmiR-NC group and AdmiR-133b group, and rat models of myocardial I/R were established in the latter 3 groups with myocardial injections of saline or recombinant adenoviruses in the left ventricle. The expression of MiR-133b was detected using RT-qPCR, and cardiac function of the rats was determined using FDP 1 HRV and BRS analysis system. Serum CK-MB and cTnI levels were determined by ELISA, myocardial injury was evaluated with HE staining, cardiomocyte apoptosis was detected by flow cytometry, and ROS content was determined using a DCFH-DA probe. In the in vitro experiment, H9C2 myocardial cells with hypoxia/reoxygenation (H/R) treatment were transfected with Mir-NC or MiR-133b mimic, and the cellular expression of MiR-133b, cell apoptosis, and ROS content were determined. Dual luciferase reporter assay was performed to verify the targeting relationship between miR-133b and YES1. The effects of pc-YES1 or miR-133b mimic transfection on YES1 expression, apoptosis, and ROS content in H9C2 cells were evaluated.@*RESULTS@#Compared with those in I/R group, miR-133b expression was obviously up-regulated, LVEDP, cTnI and CK-MB levels were significantly decreased, and LVSP, +dp/dt, -dp/dt, HR and CF levels were increased in admiR-133b group (@*CONCLUSIONS@#miR-133b can inhibit I/R-induced myocardial cell apoptosis and ROS accumulation by targeting YES1 to reduce myocardial I/R injury in rats.


Subject(s)
Animals , Apoptosis , MicroRNAs/genetics , Myocardial Reperfusion Injury , Myocytes, Cardiac , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species
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