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1.
Int. j. cardiovasc. sci. (Impr.) ; 35(1): 113-122, Jan.-Feb. 2022. graf
Article in English | LILACS | ID: biblio-1356305

ABSTRACT

Abstract ST elevation myocardial infarction (STEMI) is a highly prevalent condition worldwide. Reperfusion therapy is strongly associated with the prognosis of STEMI and must be performed with a high standard of quality and without delay. A systematic review of different reperfusion strategies for STEMI was conducted, including randomized controlled trials that included major cardiovascular events (MACE), and systematic reviews in the last 5 years through the PRISMA ( Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology. The research was done in the PubMed and Cochrane Central Register of Controlled Trials databases, in addition to a few manual searches. After the exclusion criteria were applied, 90 articles were selected for this review. Despite the reestablishment of IRA patency in PCI for STEMI, microvascular lesions occur in a significant proportion of these patients, which can compromise ventricular function and clinical course. Several therapeutic strategies - intracoronary administration of nicorandil, nitrates, melatonin, antioxidant drugs (quercetin, glutathione), anti-inflammatory substances (tocilizumab [an inhibitor of interleukin 6], inclacumab, P-selectin inhibitor), immunosuppressants (cyclosporine), erythropoietin and ischemic pre- and post-conditioning and stem cell therapy - have been tested to reduce reperfusion injury, ventricular remodeling and serious cardiovascular events, with heterogeneous results: These therapies need confirmation in larger studies to be implemented in clinical practice


Subject(s)
Prognosis , Myocardial Reperfusion/methods , Reperfusion Injury , ST Elevation Myocardial Infarction/therapy , Stents , Thrombolytic Therapy , Health Strategies , Thrombectomy , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Electrocardiography/methods , Purinergic P2Y Receptor Antagonists , Ischemic Postconditioning , Fibrinolytic Agents/therapeutic use , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/rehabilitation , Dual Anti-Platelet Therapy , Myocardial Revascularization
2.
Rev. Assoc. Med. Bras. (1992) ; 68(1): 87-93, Jan. 2022. tab, graf
Article in English | LILACS | ID: biblio-1360707

ABSTRACT

SUMMARY OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effect and mechanism of action of artichoke leaf extract in hepatic ischemia/reperfusion injury. METHODS: Rats were divided into three groups such as sham, control, and artichoke leaf extract groups. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum obtained from the subjects. Histopathological findings were scored semiquantitatively. RESULTS: Statistically, the antioxidant activity was highest in the artichoke leaf extract group, the difference in biochemical parameters and C-reactive protein was significant compared with the control group, and the histopathological positive effects were found to be significantly higher. CONCLUSIONS: As a result, artichoke leaf extract had a hepatoprotective effect and that this effect was related to the antioxidant and anti-inflammatory effects of artichoke.


Subject(s)
Animals , Rats , Reperfusion Injury/prevention & control , Reperfusion Injury/drug therapy , Cynara scolymus , Plant Extracts/therapeutic use , Plant Extracts/pharmacology , Liver , Antioxidants/metabolism , Antioxidants/therapeutic use , Antioxidants/pharmacology
3.
Einstein (Säo Paulo) ; 20: eRB6181, 2022. tab
Article in English | LILACS | ID: biblio-1364795

ABSTRACT

ABSTRACT Ischemia-reperfusion injury is a pathophysiological event occuring after abdominal organ transplantation, and has a significant influence on prognosis and survival of the graft. It is involved in delaying the primary function or non-functioning of the graft. The objective of this study was to provide information on heat shock protein mechanisms in ischemia-reperfusion injuries in abdominal organ transplantations, and to indicate the possible factors involved that may influence the graft outcome. Several classes of heat shock proteins are part of the ischemia and reperfusion process, both as inflammatory agonists and in protecting the process. Studies involving heat shock proteins enhance knowledge on ischemia-reperfusion injury mitigation processes and the mechanisms involved in the survival of abdominal grafts, and open space to support therapeutic future clinical studies, minimizing ischemia and reperfusion injuries in abdominal organ transplantations. Expression of heat shock proteins is associated with inflammatory manifestations and ischemia-reperfusion injuries in abdominal organ transplantations and may influence graft outcomes.


Subject(s)
Reperfusion Injury , Organ Transplantation , Heat-Shock Proteins/metabolism , Ischemia
4.
Article in English | WPRIM | ID: wpr-929000

ABSTRACT

OBJECTIVES@#Acute kidney injury (AKI) can be caused by ischemia/reperfusion (I/R), nephrotoxin, and sepsis, with poor prognosis and high mortality. Leptin is a protein molecule that regulates the body's energy metabolism and reproductive activities via binding to its specific receptor. Leptin can inhibit cardiomyocyte apoptosis caused by I/R, but its effect on I/R kidney injury and the underlying mechanisms are still unclear. This study aims to investigate the effect and mechanisms of leptin on renal function, renal histopathology, apoptosis, and autophagy during acute I/R kidney injury.@*METHODS@#Healthy adult male mice were randomly divided into 4 groups: a sham+wild-type mice (ob/+) group, a sham+leptin gene-deficient mice (ob/ob) group, an I/R+ob/+ group, and an I/R+ob/ob group (n=8 per group). For sham operation, a longitudinal incision was made on the back of the mice to expose and separate the bilateral kidneys and renal arteries, and no subsequent treatment was performed. I/R treatment was ischemia for 30 min and reperfusion for 48 h. The levels of BUN and SCr were detected to evaluate renal function; HE staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe cell apoptosis, and apoptosis-positive cells were counted; Western blotting was used to detect levels of apoptosis-related proteins (caspase 3, caspase 9), autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), LC3 I, LC3 II], mTOR-dependent signaling pathway proteins [phosphate and tension homology (PTEN), adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (AKT), extracellular regulated protein kinase (ERK), phosphorylated PTEN (p-PTEN), phosphorylated AMPK (p-AMPK), phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK)].@*RESULTS@#There was no significant difference in the levels of BUN and SCr between the sham+ob/+ group and the sham+ob/ob group (both P>0.05). The levels of BUN and SCr in the I/R+ob/+ group were significantly higher than those in the sham+ob/+ group (both P<0.05). Compared with the mice in the sham+ob/ob group or the I/R+ob/+ group, the levels of BUN and SCr in the I/R+ob/ob group were significantly increased (all P<0.05). There was no obvious damage to the renal tubules in the sham+ob/+ group and the sham+ob/ob group. Compared with sham+ob/+ group and sham+ob/ob group, both the I/R+ob/+ group and the I/R+ob/ob group had cell damage such as brush border shedding, vacuolar degeneration, and cast formation. Compared with the I/R+ob/+ group, the renal tubules of the mice in the I/R+ob/ob group were more severely damaged. The pathological score of renal tubular injury showed that the renal tubular injury was the most serious in the I/R+ob/ob group (P<0.05). Compared with the sham+ob/+ group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, the ratio of LC3 II to LC3 I was significantly increased, and the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/+ group (all P<0.05). Compared with the sham+ob/ob group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, and the ratio of LC3 II to LC3 I was significantly increased, while the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/ob group (all P<0.05). Compared with the I/R+ob/+ group, the levels of p-mTOR, p-PTEN, p-AMPK, p-AKT were more significantly down-regulated, while the levels of caspase 3, caspase 9, PTEN, and LC3 II were more significantly up-regulated, and the ratio of LC3 II to LC3 I was more significantly increase in the I/R+ob/ob group (all P<0.05).@*CONCLUSIONS@#Renal function and tubular damage, and elevated levels of apoptosis and autophagy are observed in mice kidneys after acute I/R. Leptin might relieve I/R induced AKI by inhibiting apoptosis and autophagy that through a complex network of interactions between mTOR-dependent signaling pathways.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Acute Kidney Injury/pathology , Animals , Apoptosis , Apoptosis Regulatory Proteins/pharmacology , Autophagy , Caspase 3/metabolism , Caspase 9/metabolism , Female , Humans , Ischemia , Kidney/pathology , Leptin/pharmacology , Male , Mammals/metabolism , Mice , Proto-Oncogene Proteins c-akt/metabolism , Reperfusion/adverse effects , Reperfusion Injury/metabolism , TOR Serine-Threonine Kinases/metabolism
5.
Article in English | WPRIM | ID: wpr-928942

ABSTRACT

OBJECTIVE@#To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons.@*METHODS@#The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway.@*RESULTS@#MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01).@*CONCLUSION@#TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.


Subject(s)
Animals , Beclin-1 , Brain Ischemia/metabolism , Glucose , Infarction, Middle Cerebral Artery/drug therapy , Mammals/metabolism , Neuroprotection , Neuroprotective Agents/therapeutic use , Oxygen , Panax notoginseng , Proto-Oncogene Proteins c-akt/metabolism , Rats , Reperfusion Injury/metabolism , Saponins/therapeutic use , TOR Serine-Threonine Kinases/metabolism
6.
Article in English | WPRIM | ID: wpr-939794

ABSTRACT

OBJECTIVES@#To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats.@*METHODS@#The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of α7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively.@*RESULTS@#ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the α7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01).@*CONCLUSION@#ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.


Subject(s)
Acetylcholinesterase , Animals , Autophagy , Brain Ischemia/metabolism , Cerebral Infarction , Cognitive Dysfunction/drug therapy , Glutathione/metabolism , Glycosides , Infarction, Middle Cerebral Artery/drug therapy , Neuroprotective Agents/therapeutic use , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Stroke/drug therapy , Superoxide Dismutase/metabolism , alpha7 Nicotinic Acetylcholine Receptor
7.
Article in Chinese | WPRIM | ID: wpr-928186

ABSTRACT

Mitochondrion, as the main energy-supply organelle, is the key target region that determines neuronal survival and death during ischemia. When an ischemic stroke occurs, timely removal of damaged mitochondria is very important for improving mitochondrial function and repairing nerve damage. This study investigated the effect of ligustilide(LIG), an active ingredient of Chinese medicine, on mitochondrial function and mitophagy based on the oxygen and glucose deprivation/reperfusion(OGD/R)-induced injury model in HT22 cells. By OGD/R-induced injury model was induced in vitro, HT22 cells were pre-treated with LIG for 3 h, and the cell viability was detected by the CCK-8 assay. Immunofluorescence and flow cytometry were used to detect indicators related to mitochondrial function, such as mitochondrial membrane potential, calcium overload, and reactive oxygen species(ROS). Western blot was used to detect the expression of dynamin-related protein 1(Drp1, mitochondrial fission protein) and cleaved caspase-3(apoptotic protein). Immunofluorescence was used to observe the co-localization of the translocase of outer mitochondrial membrane 20(TOMM20, mitochondrial marker) and lysosome-associated membrane protein 2(LAMP2, autophagy marker). The results showed that LIG increased the cell viability of HT22 cells as compared with the conditions in the model group. Furthermore, LIG also inhibited the ROS release, calcium overload, and the decrease in mitochondrial membrane potential in HT22 cells after OGD/R-induced injury, facilitated Drp1 expression, and promoted the co-localization of TOMM20 and LAMP2. The findings indicate that LIG can improve the mitochondrial function after OGD/R-induced injury and promote mitophagy. When mitophagy inhibitor mdivi-1 was administered, the expression of apoptotic protein increased, suggesting that the neuroprotective effect of LIG may be related to the promotion of mitophagy.


Subject(s)
4-Butyrolactone/analogs & derivatives , Apoptosis , Calcium/pharmacology , Glucose/metabolism , Humans , Mitochondrial Proteins , Mitophagy , Reactive Oxygen Species/metabolism , Reperfusion Injury/genetics
8.
Article in Chinese | WPRIM | ID: wpr-927892

ABSTRACT

Objective: To investigate the effects of Zhongfeng capsule on the autophagy-related proteins expression in rats with cerebral ischemia/reperfusion injury (CI/ RI), and to explore its neural protection mechanisms of the decoction. Methods: Rat middle cerebral artery ischemia/reperfusion injury model (ischemia for 2 h, reperfusion for 24 h) was prepared by the improved line plug method. Sixty male SD rats were randomly divided into sham operation group, model group, butylphthalide group(0.054 g/kg), Zhongfeng capsule high-dose groups (1.08 g/kg), Zhongfeng capsule middle-dose groups (0.54 g/kg), Zhongfeng capsule low-dose groups (0.27 g/kg), with 10 rats in each group. Rats were treated with Zhongfeng capsule by gavage once a day for 10 days. The rats were sacrificed and the brain tissue was obtained after the experiment in each group. Score neurological deficit was evaluated after 24 h of the last intervention in rat of each group. The pathological changes of brain tissue were observed by HE staining. The serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were determined by ELISA. The expressions of key genes and proteins of PI3K/Akt/Beclin1 signaling pathway in brain tissue were detected by qRT-PCR and Western blot respectively. Results: Compared with the sham operation group, the body weight and protein expressions of p-PI3k and p-Akt in brain tissue of rats were decreased significantly in the model group, while the brain index, neurological deficit score, gene and protein expressions of Beclin1 and LC3 were increased markedly in the model group(P<0.05 or P<0.01). In the model group, nerve cells of brain tissue were loosely packed, interstitial edema, triangular in shape, nuclear pyknosis and dark-blue staining were observed. Compared with the model group, the body weight of rats was increased obviously, the neurological deficit score was decreased significantly and the pathological injury of brain tissue was alleviated evidently in high-dose of Zhongfeng capsule group (P<0.05). The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P<0.05 or P<0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P<0.05 or P<0.01). Conclusion: Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.


Subject(s)
Animals , Autophagy-Related Proteins/pharmacology , Beclin-1/metabolism , Body Weight , Brain , Brain Ischemia/metabolism , Male , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy
9.
Acta Physiologica Sinica ; (6): 320-332, 2022.
Article in Chinese | WPRIM | ID: wpr-927608

ABSTRACT

Renal ischemia-reperfusion injury (IRI) is histologically characterized by tubular cell death. Diverse pathways of regulated cell death (RCD) have been reported to contribute to renal IRI in recent studies. In this review, we discuss the signaling pathways, regulators and crosstalk of RCD, including necroptosis, ferroptosis and pyroptosis, and their role in renal IRI in order to pave the way for new therapeutic opportunities.


Subject(s)
Apoptosis , Ferroptosis , Humans , Kidney/metabolism , Necroptosis , Regulated Cell Death , Reperfusion Injury/drug therapy
10.
Acta Physiologica Sinica ; (6): 39-46, 2022.
Article in Chinese | WPRIM | ID: wpr-927579

ABSTRACT

Acute kidney injury (AKI) is a common clinical syndrome and an independent risk factor of chronic kidney disease and end-stage renal failure. At present, the treatments of AKI are still very limited and the morbidity and mortality of AKI are rising. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs (circRNAs), are RNAs that are transcribed from the genome, but not translated into proteins. It has been widely reported that ncRNA is involved in AKI caused by ischemia reperfusion injury (IRI), drugs and sepsis through different molecular biological mechanisms, such as apoptosis and oxidative stress response. Therefore, ncRNAs are expected to become a new target for clinical prevention and treatment of AKI and a new biomarker for early warning of the occurrence and prognosis of AKI. Here, the role and mechanism of ncRNA in AKI and the research progress of ncRNA as biomarkers are reviewed.


Subject(s)
Acute Kidney Injury/metabolism , Humans , MicroRNAs/metabolism , RNA, Circular , RNA, Long Noncoding/genetics , RNA, Untranslated/genetics , Reperfusion Injury/genetics
11.
Acta Physiologica Sinica ; (6): 28-38, 2022.
Article in Chinese | WPRIM | ID: wpr-927578

ABSTRACT

Acute kidney injury (AKI) is a common critical clinical disease characterized by a sharp decline of renal function. Ischemia-reperfusion (IR) is one of the main causes of AKI. The mortality of AKI remains high due to the lack of early diagnosis and cause specific treatment. IR rapidly initiates innate immune responses, activates complement and innate immune cells, releasing a large number of injury-related molecules such as high mobility group box-1 (HMGB1), inflammatory mediators such as caspase-3, and then recruits immune inflammatory cells including M1 macrophages (Mϕ) to the microenvironment of injury, causing apoptosis and necrosis of renal tubular epithelial cells (TECs). Dead cells and associated inflammation further activate the adaptive immune system, which not only aggravates tissue damage, but also initiates M2 Mϕ participated inflammatory clearance, tissue repair and regeneration. Mϕ, professional phagocytes, and TECs, semi-professional phagocytes, can phagocytose around damaged cells including apoptotic Mϕ and TECs, which are key innate immune cells to regulate the outcome of injury, repair or fibrosis. In recent years, it has been found that erythropoietin (EPO) not only binds to the homodimeric receptor (EPOR)2 to induce erythropoiesis, but also binds to the heterodimeric receptor EPOR/βcR, also known as innate repair receptor, which plays renoprotective roles. Properdin is the only positive regulator in the complement activation of alternative pathway. It also can effectively identify and bind to early apoptotic T cells and facilitate phagocytic clearing by Mϕ through a non-complement activation-dependent mechanism. Our previous studies have shown that Mϕ and TECs associated with EPO and its receptors and properdin are involved in IR injury and repair, but the underlying mechanism needs to be further explored. As an important carrier of cell-to-cell signal transmission, exosomes participate in the occurrence and development of a variety of renal diseases. The role of exosomes involved in the interaction between Mϕ and TECs in IR-induced AKI is not fully defined. Based on the available results in the role of Mϕ and TECs in renal IR-induced AKI, this review discussed the role of Mϕ polarization and interaction with TECs in renal IR injury, as well as the participation of EPO and its receptors, properdin and exosomes.


Subject(s)
Acute Kidney Injury/metabolism , Animals , Epithelial Cells/metabolism , Humans , Ischemia/metabolism , Kidney , Macrophages/physiology , Mice , Mice, Inbred C57BL , Reperfusion , Reperfusion Injury
12.
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
13.
Arq. bras. cardiol ; 117(2): 290-297, ago. 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1339163

ABSTRACT

Resumo Fundamento: O núcleo do trato solitário (NTS) é uma área do cérebro que desempenha um papel fundamental na regulação renal e cardiovascular através dos impulsos dos barorreceptores. Objetivos: O objetivo deste estudo foi avaliar o efeito da Naringina (NAR) e trimetazidina (TMZ), isoladamente e combinadas, na atividade elétrica do NTS e na sensibilidade barorreflexa (SBR) na lesão de isquemia e reperfusão (I/R) renal. Métodos: Foram utilizados quarenta ratos machos Sprague-Dawley (200-250 g), alocados em 5 grupos com 8 ratos cada. Grupos: 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; e 5) TMZ5 + NAR100. A veia femoral esquerda foi canulada para infundir a solução salina ou droga e avaliar a SBR. A I/R foi induzida por oclusão dos pedículos renais por 45 min, seguida de reperfusão de 4 horas. O eletroencefalograma local do NTS foi registrado antes, durante a isquemia e durante a reperfusão. A fenilefrina foi injetada por via intravenosa para avaliar a SBR ao final do tempo de reperfusão. Os dados foram analisados por ANOVA de duas vias com medidas repetidas seguida pelo teste post hoc de Tukey. Um valor de p<0,05 foi considerado como significativo. Resultados: As ondas elétricas do NTS não se alteraram durante o tempo de isquemia, mas diminuíram significativamente durante todos os tempos de reperfusão. A atividade elétrica do NTS e a SBR foram reduzidas drasticamente em ratos com lesão I/R; no entanto, a administração de NAR e TMZ, isoladamente e combinadas, melhorou significativamente essas alterações em ratos com lesão I/R. Conclusões: Os resultados mostraram que a lesão de I/R leva à redução da atividade elétrica da SBR e do NTS, e pode haver uma ligação entre a I/R e a diminuição da SBR. Além disso, a NAR e a TMZ são agentes promissores para tratar complicações de I/R.


Abstract Background: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses. Objectives: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury. Methods: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant. Results: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury. Conclusions: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.


Subject(s)
Animals , Male , Rats , Trimetazidine/pharmacology , Reperfusion Injury/prevention & control , Reperfusion Injury/drug therapy , Rats, Sprague-Dawley , Solitary Nucleus , Baroreflex , Flavanones , Kidney
15.
Rev. bras. cir. cardiovasc ; 36(4): 515-521, July-Aug. 2021. tab, graf
Article in English | LILACS | ID: biblio-1347148

ABSTRACT

Abstract Objectives: Ischemia-reperfusion injury is an important cause of multiple organ failure in cardiovascular surgery. Our aim is to investigate the effect of the probiotic Saccharomyces boulardii on oxidative stress, inflammatory response, and lung injury in an experimental model of aortic clamping. Methods: Twenty-one Wistar rats were randomized into three groups (n=7). Control group animals received saline gavage for a week before undergoing median laparotomy. In other groups, supraceliac aorta was clamped for 45 minutes to induce ischemia followed by reperfusion for 60 minutes. In the ischemia-reperfusion group, saline gavage was given preoperatively for one week. Ischemia-reperfusion+probiotic group rats received probiotic gavage for seven days before aortic clamping. The levels of oxidative stress markers and pro-inflammatory cytokines were determined in both serum and lung tissue samples. Ileum and lung tissues were harvested for histological examination. Results: Ischemia-reperfusion caused severe oxidative damage and inflammation evident by significant increases in malondialdehyde and cytokine levels (tumor necrosis factor alpha and interleukin-1 beta) and decreased glutathione levels in both serum and lung tissues. There was severe histological tissue damage to the lung and ileum in the ischemia-reperfusion group. Probiotic pretreatment before aortic clamping caused significant suppression of increases in serum and lung tissue malondialdehyde and tumor necrosis factor alpha levels. Histological damage scores in tissue samples decreased in the ischemia-reperfusion+probiotic group (P<0,005). Conclusions: Oral supplementation of probiotic S. boulardii before supraceliac aortic ischemia-reperfusion in rats alleviates lung injury by reducing oxidative stress, intestinal cellular damage, and modulation of inflammatory processes.


Subject(s)
Animals , Rats , Reperfusion Injury/prevention & control , Probiotics/therapeutic use , Lung Injury , Saccharomyces boulardii , Aorta , Cytokines , Rats, Wistar , Oxidative Stress , Lung
16.
Braz. j. med. biol. res ; 54(4): e10498, 2021. graf
Article in English | LILACS | ID: biblio-1153543

ABSTRACT

It is known that neuronal apoptosis contributes to pathology of cerebral ischemia injury. Zonisamide (ZNS) has shown anti-apoptosis effects in recent studies. The present study investigated whether the anti-apoptotic effect can account for the neuroprotective action of ZNS on cerebral ischemia. Neuronal cells were maintained under oxygen-glucose deprivation conditions to simulate cerebral ischemia and treated with ZNS simultaneously. The apoptosis of the cells and expression of apoptosis-related proteins were investigated by flow cytometry and western blot analysis, respectively. A cerebral ischemia mouse model was created via middle cerebral artery occlusion, and the mice were treated with ZNS. Neurological deficit scores and infarct volumes of the cerebral ischemia mice were measured. The apoptosis status of the neuronal cells was evaluated by TUNEL staining. In vitro, the ZNS treatment inhibited both the apoptosis of the neuronal cells and apoptosis-related protein expression (caspase-3, caspase-8, and calpain-1) induced by the oxygen-glucose deprivation. The anti-apoptosis effect of ZNS could occur through the blocking of reactive oxygen species. Moreover, ZNS treatment significantly ameliorated neurological deficits and reduced infarct volumes in the cerebral ischemia mice model. In this study, ZNS exerted neuroprotective effects by inhibition of apoptosis in neuronal cells in cerebral ischemia. Therefore, ZNS might be a promising therapy for cerebral ischemia.


Subject(s)
Animals , Rats , Reperfusion Injury , Brain Ischemia/drug therapy , Neuroprotective Agents/pharmacology , Apoptosis , Infarction, Middle Cerebral Artery/drug therapy , Zonisamide/pharmacology
17.
Braz. j. med. biol. res ; 54(10): e11028, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285653

ABSTRACT

Engeletin is a natural derivative of Smilax glabra rhizomilax that exhibits anti-inflammatory activity and suppresses lipid peroxidation. In the present study, we sought to elucidate the mechanistic basis for the neuroprotective and pro-angiogenic activity of engeltin in a human umbilical vein endothelial cells (HUVECs) oxygen-glucose deprivation and reoxygenation (OGD/R) model system and a middle cerebral artery occlusion (MCAO) rat model of cerebral ischemia and reperfusion injury. These analyses revealed that engeletin (10, 20, or 40 mg/kg) was able to reduce the infarct volume, increase cerebral blood flow, improve neurological function, and bolster the expression of vascular endothelial growth factor (VEGF), vasohibin-2 (Vash-2), angiopoietin-1 (Ang-1), phosphorylated human angiopoietin receptor tyrosine kinase 2 (p-Tie2), and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in MCAO rats. Similarly, engeletin (100, 200, or 400 nM) markedly enhanced the migration, tube formation, and VEGF expression of HUVECs in an OGD/R model system, while the VEGF receptor (R) inhibitor axitinib reversed the observed changes in HUVEC tube formation activity and Vash-2, VEGF, and CD31 expression. These data suggested that engeletin exhibited significant neuroprotective effects against cerebral ischemia and reperfusion injury in rats, and improved cerebrovascular angiogenesis by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways.


Subject(s)
Animals , Rats , Reperfusion Injury/prevention & control , Brain Ischemia/prevention & control , Infarction, Middle Cerebral Artery , Endothelial Cells , Flavonols , Angiopoietin-1 , Vascular Endothelial Growth Factors , Vascular Endothelial Growth Factor A , Glycosides
18.
Acta cir. bras ; 36(3): e360305, 2021. tab, graf
Article in English | LILACS | ID: biblio-1248535

ABSTRACT

ABSTRACT Purpose To evaluate the effect of creatine supplementation in the diet of rats subjected to ischemia and reperfusion of hind limbs. Methods Eighteen male Wistar rats were randomized to receive dietary creatine supplementation (G1) or no supplementation (G2), before being subjected to 4 h of ischemia followed by 4 h of reperfusion. In addition, 10 rats (G3) underwent the same surgical procedure, without ischemia, but with supplementation. After reperfusion, kidney and musculature were evaluated for histological damage and serum levels of alanine aminotransferase, urea and creatinine were obtained. Results The urea dosage showed significant differences between the groups (averages G1 = 155.1; G2 = 211.27; G3 = 160.42). Histological analysis found significant differences between G1 and G2 (but not between G1 and G3) in renal myoglobin cylinders and vacuolar degeneration variables and in hypereosinophilia and karyopyknosis variables in muscle fibers. There were no significant differences in the other variables studied. Conclusions Creatine supplementation was related to fewer histological lesions, as well as lower levels of plasma urea, which may suggest a protective effect against lesions caused by ischemia and reperfusion of posterior paws muscles in Wistar rats.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/prevention & control , Creatine , Reperfusion , Rats, Wistar , Muscle, Skeletal , Dietary Supplements , Diet , Ischemia , Kidney
19.
Acta cir. bras ; 36(1): e360101, 2021. tab, graf
Article in English | LILACS | ID: biblio-1152694

ABSTRACT

ABSTRACT Purpose: The aim of this study is to compare the hepatic protective effect of both remote and local postconditioning (POS). Methods: Twenty-eight Wistar rats were assigned into four groups: sham group(SHAM), ischemia-reperfusion group (IR), local ischemic POS group (lPOS) and remote ischemic POS group (rPOS). Animals were subjected to liver ischemia for 30 min. Local ischemic POS group consisted of four cycles of 5 min liver ischemia, followed by 5 min reperfusion (40 min). Remote ischemic POS group consisted of four cycles of 5 min hind limb ischemia, followed by 5 min hind limb perfusion after the main liver ischemia period. After 190 minutes median and left liver lobes were harvested for biochemical and histopathology analysis. Results: All the conditioning techniques were able to increase the level of bothglutathione reductase and peroxidase, showing higher values in the rPOS group when compared to the lPOS. Also, thiobarbituric acid reactive substances were higher in all intervention groups when compared to SHAM, but rPOS had the lower rates of increase, showing the best result. The histopathology analysis showed that all groups had worst injury levels than SHAM, but rPOS had lower degrees of damage when compared to the lPOS, although it was not statistically significant. Conclusion: Remote postconditioning is a promising technique to reduce liver ischemia-reperfusion injury, once it increased antioxidants substances and reduced the damage.


Subject(s)
Animals , Rats , Reperfusion Injury/prevention & control , Ischemic Preconditioning , Ischemic Postconditioning , Rats, Wistar
20.
Acta cir. bras ; 36(1): e360104, 2021. tab, graf
Article in English | LILACS | ID: biblio-1152690

ABSTRACT

ABSTRACT Purpose: To evaluate the protective effect of dexmedetomidine on gastric injury induced by ischemia reperfusion (I/R) in rats. Methods: A total of 18 male albino Wistar rats were divided groups as: gastric ischemia reperfusion (GIR), gastric ischemia reperfusion and 50 μg/kg dexmedetomidine (DGIR) and sham operation (HG) group. After the third hour of reperfusion, the biochemical and histopathological examinations were performed on the removed stomach tissue. Results: Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were found to be significantly higher in GIR compared to HG (p < 0.05). A statistically significant decrease was observed at the DGIR compared to the GIR for oxidants levels. Total glutathione (tGSH) and superoxide dismutase (SOD) levels were statistically significantly decreased at the GIR, and antioxidants levels were found to be significantly higher in the DGIR (p < 0.05) There was no significant difference between HG and DGIR in terms of SOD (p = 0.097). The DGIRs' epitheliums, glands and vascular structures were close to normal histological formation. Conclusions: Dexmedetomidine is found to prevent oxidative damage on the stomach by increasing the antioxidant effect. These results indicate that dexmedetomidine may be useful in the treatment of ischemia-reperfusion-related gastric damage.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/prevention & control , Reperfusion Injury/drug therapy , Dexmedetomidine/pharmacology , Stomach , Superoxide Dismutase , Rats, Wistar , Malondialdehyde , Antioxidants/pharmacology
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