scholarly journals Effects of Aspirin on Myocardial Ischemia-Reperfusion Injury in Rats through STAT3 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Zhenjun Wu ◽  
Xuewen Li ◽  
Xiuyue Li ◽  
Lihua Yu
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Sham Operation ◽  
Expression Levels ◽  
Sham Operation Group ◽  
Stat3 Signaling Pathway ◽  
Operation Group ◽  
Myocardial Ischemia Reperfusion ◽  
Aspirin Group

Objective. To investigate the role and mechanism of aspirin in myocardial injury induced by myocardial ischemia-reperfusion in rats through STAT3 signaling pathway. Methods. Sixty rats were randomly divided into three groups: the sham operation group, MI/R group, and MI/R+aspirin group (aspirin group). The rats in the sham operation group did not ligate the LAD coronary artery, while the aspirin group ligated the LAD coronary artery, which caused the suture to be loosened after 30 minutes ischemia, and 60 mg/kg aspirin was injected into the tail vein 10 minutes before reperfusion. After three hours of reperfusion, the ultrasound system was used to collect hemodynamic parameters, including ejection fraction (EF%), shortening fraction (FS%), and left ventricular end-systolic pressure (LVESP%) and left ventricular end-diastolic pressure (LVEDP%). Finally, the rats were euthanized; then, blood samples were taken for biochemical examination, myocardial tissue was collected, and the left ventricle was used for subsequent experiments. The gene expression levels of Bax and Bcl-2 were detected by PCR. The protein expression levels of Bcl-2, Bax, p-JAK2, total JAK2, p-STAT3, and total STAT3 were detected by Western blot. Results. Compared with the sham operation group and the aspirin group, the area of myocardial infarction in the MI/R was significantly increased ( p < 0.05 ). In terms of hemodynamic parameters, LVEDP was significantly elevated in the MI/R group. The results of PCR showed that compared with the MI/R group, the mRNA expression of Bax in the aspirin group was significantly decreased, while that of Bcl-2 was significantly increased ( p < 0.05 ). Western blot analysis showed that compared with the MI/R group, aspirin pretreatment significantly increased the expression levels of p-STAT3 and p-JAK2 ( p < 0.05 ). Conclusion. The mechanism of aspirin preconditioning to protect the heart from MI/R injury appears to be related to JAK2/STAT3 and related to the activation of the signaling pathway.

scholarly journals Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2/STAT3 signaling pathway in mice during sevoflurane anesthesia

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Xiao-Juan Xie ◽  
Dong-Mei Fan ◽  
Kai Xi ◽  
Ya-Wei Chen ◽  
Peng-Wei Qi ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Protein Expression ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Inhalation Anesthesia ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Myocardial Ischemia Reperfusion

The study aims to explore the effects of miR-135b-5p on myocardial ischemia/reperfusion (I/R) injuries by regulating Janus protein tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by terminal dexynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay. MiR-135b-5p expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein B (Bax) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Target relationship between miR-135b-5p and JAK2 was confirmed by dual-luciferase reporter assay. The other five groups exhibited increased cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, mRNA expression of JAK2 and STAT3, and protein expression of p-STAT3 and p-JAK2 compared with the sham group, but showed decreased LVEF, LVFS, and Bcl-2 expression. Compared with the model and AG490 + Sevo groups, the Sevo, inhibitor + Sevo and inhibitor + AG490 + Sevo groups displayed reduced cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, but displayed elevated mRNA expression of JAK2 and STAT3, protein expression of p-STAT3 and p-JAK2, LVEF, LVFS and Bcl-2 expression. Compared with the Sevo and inhibitor + AG490 + Sevo groups, the AG490 + Sevo group showed decreased LVEF, LVFS, Bcl-2 expression, mRNA expressions of JAK2 and STAT3, and protein expressions of p-STAT3 and p-JAK2, but increased cardiomyocyte necrosis, apoptosis, and Bax expressions. MiR-135b-5p negatively targetted JAK2. Inhibition of miR-135b-5p can protect against myocardial I/R injury by activating JAK2/STAT3 signaling pathway through mediation of inhalation anesthesia with sevoflurane.

P0538HYPERIN PREVENTS ISCHEMIC/REPERFUSION AKI VIA STK40

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yan Xu ◽  
Yue Zhang
Keyword(s):  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Normal Group ◽  
Sham Operation ◽  
In Vitro Experiments ◽  
Rt Pcr ◽  
Sham Operation Group ◽  
Tnf Α ◽  
Operation Group

Abstract Background and Aims Ischemia-reperfusion injury (IRI) is the outcome of an inflammatory process and tubular cell death that is triggered by undergoing a transient reduction or cessation of blood flow and following by reperfusion. Unresolved IRI can contribute to chronic kidney disease even death. Our aims is to investigate the protective effect of hyperin on ischemia-reperfusion renal injury (IRI) and its possible mechanism. Method ① The transcriptome chip data of multiple IRI models were selected from the NCBI GEO DateSets database and a number of key proteins that could participate in IRI were screened out (the fold increase was greater than 2 fold and was statistically significant). Network and transcript binding motif analysis was performed to determine the best binding protein. ② C57BL / 6J mice were selected and randomly divided into normal group, sham operation group, IRI group (bilateral renal pedicle clamping for 45min), hyperin + IRI group (50mg / kg.d per day, 7 days before surgery ), DMSO + IRI group (7 days before the operation, the same amount of DMSO was administered to the stomach every day, and the operation was the same as AKI), with 6 rats in each group. Renal tissue and blood were collected 24 hours after operation for testing. ③ In vitro experiments, human proximal tubule epithelial cells (HK-2) were selected and divided into hypoxia 3, 6, 9, 12, 24, 36, and 48h for reoxygenation of 1, 3, and 6h respectively. Relevant indicators for RT-PCR detection were determined Optimal hypoxia time. The drug safe concentration was selected according to 0, 5, 10, 25, 50, 100, 200, 400 μg / ml hyperin pre-treatment for 12 hours, and the CCK8 reagent was added for 2 hours to measure the absorbance at 450 nm. The cells were randomly divided into normal group, hypoxia group, hypoxia + DMSO group, hypoxia + hyperin group, and related indexes were detected by RT-PCR and Western Blot. ④ Obtain the tertiary structure of the protein and the three-dimensional structure of the hyperin molecule from the RCSB Protein Data Bank website and the PubChem compound database, and use molecular docking technology to determine the proteins that can bind to hyperin using autodock software and analyze their binding ability. Results Bioinformatics analysis suggested that STK40 protein is one of the key factors of IRI and may be a target for preventing and treating diseases. In vivo experiments showed that compared with the normal group and the sham operation group, the levels of serum creatinine, blood urea nitrogen, and kim-1 in rats were significantly increased after AKI, and HE staining of pathological sections showed an increase in renal tubular injury scores. Significantly decreased (P&lt;0.05); RT-PCR results showed that kim-1, caspase-3, NF-κB, IL-6, TNF-α increased significantly after AKI, STK40, Bcl2 / BAX decreased, and the above after hyperin The indicators changed in opposite directions (P &lt;0.05). In vitro experiments: The best time for hypoxia is 24h hypoxia + 1h reoxygenation; compared with the control group, the drug concentration is &lt;100 μg / mL and the cell proliferation activity rate is&gt; 90%, so the hyperin concentration was selected as 50 μg / mL (P &lt; 0.05); RT-PCR results showed that Hif1-α, caspase-3, NF-κB, IL-6, TNF-α significantly increased, and STK40, Bcl2 / BAX decreased compared with the normal group. After administration of hyperin, the above indexes changed in opposite directions (P &lt;0.05). Conclusion In this study, using molecular docking technology and constructing IRI mice model, it was confirmed that hyperin can reduce IRI and exert a protective effect on IRI by inhibiting STK40 expression.

scholarly journals Dexmedetomidine Attenuates Myocardial Ischemia-Reperfusion Injury in Diabetes Mellitus by Inhibiting Endoplasmic Reticulum Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jinjie Li ◽  
Ying Zhao ◽  
Nan Zhou ◽  
Longyun Li ◽  
Kai Li
Keyword(s):  
Endoplasmic Reticulum ◽  
Myocardial Ischemia ◽  
Endoplasmic Reticulum Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Sham Operation ◽  
Sham Operation Group ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Objective. With the increasing incidence of diabetes mellitus (DM) combined with myocardial ischemia, how to reduce myocardial ischemia-reperfusion injury in DM patients has become a major problem faced by clinicians. We investigated the therapeutic effects of dexmedetomidine (DEX) on myocardial ischemia-reperfusion injury in DM rats and its effect on endoplasmic reticulum stress. Methods. SD rats with SPF grade were randomly divided into 6 groups: non-DM rats were divided into the sham operation group (NDM-S group), ischemia-reperfusion group (NDM-IR group), and dexmedetomidine group (NDM-DEX group); DM rats were divided into the diabetic sham operation group (DM-S group), diabetes-reperfusion group (DM-IR group), and diabetes-dexmedetomidine (DM-DEX) group, with 10 rats in each group. Then the effects of DEX on the changes of CK-MB and cTnT levels were examined. The effects of myocardial pathological damage and myocardial infarct size were detected. The apoptosis of cardiomyocytes was detected. The apoptosis of heart tissue cells was also tested through the expressions of cleaved caspase-3, Bcl-2, and Bax proteins. The expression of endoplasmic reticulum stress-related proteins GRP78, CHOP, ERO1α, ERO1β, and PDI was examined. The hypoxia/reoxygenation (H/R) injury cell model was established, the effects of DEX, DEX+ ERS agonist on cell apoptosis was also detected. Results. The myocardial damage of DM-IR was more severe than that of NDM-IR rats. DEX could reduce the expression of CK-MB and cTnT, reduce pathological damage, and reduce scar formation and improve fibrosis. DEX can reduce the expression of GRP78, CHOP, ERO1α, ERO1β, and PDI proteins in vivo and in vitro. And the effect of DEX on cell apoptosis could be blocked by ERS agonist. Conclusion. DEX attenuates myocardial ischemia-reperfusion injury in DM rats and H/R injury cell, which is associated with the reduction of ERS-induced cardiomyocyte apoptosis.

scholarly journals Luhong Formula Has a Cardioprotective Effect on Left Ventricular Remodeling in Pressure-Overloaded Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Qian Liu ◽  
Hui-Yan Qu ◽  
Hua Zhou ◽  
Jing-Feng Rong ◽  
Tian-Shu Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Caspase 3 ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Sham Operation ◽  
Model Group ◽  
Enos Expression ◽  
Sham Operation Group ◽  
Operation Group

Background. Luhong formula (LHF)—a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd—is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis. Methods. Forty-eight SD male rats were randomly assigned into six groups (n = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-β1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-β1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope. Results. LHF significantly lowered the rat’s HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-β1, caspase-3, VEGF, and VEGFR2 expression. Conclusion. LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-β1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.

scholarly journals The Protecting Effects and Mechanisms of Baicalin and Octreotide on Heart Injury in Rats with SAP

2007 ◽  
Vol 2007 ◽  
pp. 1-11 ◽  
Author(s):  
Zhang Xiping ◽  
Tian Hua ◽  
Chen Hanqing ◽  
Chen Li ◽  
Wang Zhiwei ◽  
...  
Keyword(s):  
Protein Expression ◽  
Caspase 3 ◽  
Treated Group ◽  
Myocardial Cell ◽  
Sham Operation ◽  
Model Group ◽  
Expression Levels ◽  
Sham Operation Group ◽  
Heart Injury ◽  
Operation Group

Purpose.To observe the protecting effects and mechanisms of Baicalin and Octreotide on heart injury in rats with severe acute pancreatitis (SAP).Methods.The SAP rat models were randomly divided into the model group, Baicalin-treated group, Octreotide treated group, and sham operation group. The contents of some inflammatory indexes in blood were determined. The rat mortality, pathological changes of heart, the changes ofNF-κB, P-Selectin, Bax, Bcl-2, and Caspase-3 protein expression levels as well as apoptotic index were observed in all groups, respectively, at 3 hours, 6 hours, and 12 hours after operation.Results.The survival rate of model group was less than treated groups at 12 hours, difference was significant. The contents of some inflammatory indexes of the treated groups were lower than those of the model group to various degrees at different time points. The pathological myocardial changes under light microscope were milder in treated groups than in model group. The changes ofNF-κB, P-Selectin, Bax, Bcl-2, and Caspase-3 protein expression levels in all groups were different. There was only a case of myocardial cell apoptosis in an Octreotide-treated group at 6 hours.Conclusion.Baicalin and Octreotide have protecting effects on heart injury of rats with SAP.

scholarly journals Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling

2018 ◽  
Vol 47 (3) ◽  
pp. 1193-1206 ◽  
Author(s):  
Yunyang Lu ◽  
Yingda Feng ◽  
Dan Liu ◽  
Zhiran Zhang ◽  
Kai Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardioprotective Effect ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Production Of Hydrogen ◽  
Myocardial Ischemia Reperfusion

Background/Aims: Myocardial ischemia/reperfusion (MI/R) injury is a leading factor responsible for damage in myocardial infarction, resulting in additional injury to cardiac tissues involved in oxidative stress, inflammation, and apoptosis. Thymoquinone (TQ), the main constituent of Nigella sativa L. seeds, has been reported to possess various biological activities. However, few reports regarding myocardial protection are available at present. Therefore, this study was conducted aiming to investigate the protective effect of TQ against MI/R injury and to clarify its potential mechanism. Methods: MI/R injury models of isolated rat hearts and neonatal rat cardiomyocytes were established. The Langendorff isolated perfused heart system, triphenyltetrazolium chloride staining, gene transfection, TransLaser scanning confocal microscopy, and western blotting were employed to evaluate the cardioprotection effect of TQ against MI/R injury. Results: Compared with the MI/R group, TQ treatment could remarkably improve left ventricular function, decrease myocardial infarct size and production of lactate dehydrogenase (LDH), and attenuate mitochondrial oxidative damage by elevating superoxide dismutase (SOD) activity and reducing production of hydrogen peroxide (H2O2) and malonaldehyde (MDA). Moreover, the cardioprotective effect of TQ was accompanied by up-regulated expression of SIRT1 and inhibition of p53 acetylation. Additionally, TQ treatment could also enhance mitochondrial function and reduce the number of apoptotic cardiomyocytes. Nonetheless, the cardioprotective effect of TQ could be mitigated by SIRT1 inhibitor sirtinol and SIRT1 siRNA, respectively, which was achieved through inhibition of the SIRT1 signaling pathway. Conclusions: The findings in this study demonstrate that TQ is efficient in attenuating MI/R injury through activation of the SIRT1 signaling pathway, which can thus reduce mitochondrial oxidative stress damage and cardiomyocyte apoptosis.

Yiqi Dingxuan Yin improves cerebral ischaemic injury in rats by inhibiting apoptosis and promoting angiogenesis

2021 ◽  
Author(s):  
Fei Liu ◽  
Liuyang Xie ◽  
Chunhua Liu ◽  
Guilian He ◽  
Chunyun Yuan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cerebral Ischaemia ◽  
Neurological Function ◽  
Neural Function ◽  
Sham Operation ◽  
Nerve Function ◽  
Model Group ◽  
Expression Levels ◽  
Sham Operation Group ◽  
Operation Group

Abstract Background Clinically, Yiqi Dingxuan Yin promotes nerve function recovery and improves nerve function defect symptoms; however, the underlying molecular pathways remain unknown. In this study, we established a rat model of cerebral ischaemia induced by middle cerebral artery occlusion (MCAO). The effects of Yiqi Dingxuan Yin on the neurological function and local neuron morphology were compared with those of butylphthalide, which is used to treat ischemic stroke, and the possible mechanisms of action were explored. Methods Of 97 healthy adult male Sprague‒Dawley rats, 20 were randomly assigned to the sham operation group. The remaining rats underwent MCAO. Model generation was successful in 60 rats, which were randomly divided into a model group, butylphthalide group, and Yiqi Dingxuan Yin group (n = 20/group) administered distilled water, butylphthalide capsule, and Yiqi Dingxuan Yin, respectively. Zea-Longa scores were used to assess the neurological function of the rats at 1, 3, 7, and 14 days. Haematoxylin and eosin staining of brain sections was used to observe morphological changes in the rat hippocampus. Apoptosis of nerve cells was detected using TUNEL staining. The expression levels of erythropoietin/erythropoietin receptor (EPO/EPOR), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor/tyrosine receptor kinase B (BDNF/TrkB) protein in the ischaemic brain tissue were detected using immunohistochemistry. Results The apoptosis rate, and EPO/EPOR, VEGF, and BDNF/TrkB expression levels were higher in the model group than in the sham operation group (P < 0.05). Among MCAO groups, the nerve function deficit score and cell apoptosis rate were lower (P < 0.05), whereas the EPO/EPOR, VEGF, and BDNF/TrkB protein expression levels were higher (P < 0.05) in both the butylphthalide and Yiqi Dingxuan Yin groups than in the model group. Conclusions Yiqi Dingxuan Yin can improve the neural function and morphology of neurons after cerebral ischaemia injury in rats, with a more significant effect at 14 days. This may be related to the upregulation of EPO/EPOR, VEGF, and BDNF/TrkB protein expression, which may promote angiogenesis to improve cerebral blood flow and oxygen supply, thereby protecting the form and function of neurons and promoting the restoration of impaired neural function.

Rhein Activates Janus Protein Tyrosine Kinase2/Signal Transducer and Transcription Activation Factor3 Reduces Mitochondrial Oxidative Damage Caused by Myocardial Ischemia/Reperfusion Injury

2021 ◽  
Vol 11 (1) ◽  
pp. 89-98
Author(s):  
Jianxian Xiong ◽  
Dongmin Yu ◽  
Wentong Li ◽  
Xiaowei Wang
Keyword(s):  
Myocardial Ischemia ◽  
Glutathione Peroxidase ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Cells ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Background: Rhein is a kind of lipophilic anthraquinone widely existing in herbal medicine. Here we aim to investigate whether Rhein can reduce the degree of myocardial ischemia/reperfusion injury and inhibit the development of oxidative stress, and elucidate the molecular mechanism of Rhein in protecting myocardial cells. Methods: The anti-oxidation and anti-apoptosis effects of Rhein were studied by using the primary myocardial cells of ischemia/reperfusion rat as the model of myocardial injury. Cell viability was detected by MTT, The level of LDH and CK-MB released by cardiomyocytes was measured by Colorimetric assay. The ROS was observed under microscope and the level of catalase and glutathione peroxidase were detected by enzymatic methods. The JAK2/STAT3 signaling pathway mediated by Rhein was observed by Western blot. Results: Compared with that of the SIR group, cell viability in the SIR and Rhein co-treatment groups increased significantly (P < 0.001), the release of LDH and CK-MB decreased, the positive rate of ROS in cardiomyocytes decreased, and the concentration of catalase and glutathione peroxidase increased significantly (P < 0.001). Besides, Rhein can activate JAK2/STAT3 signaling pathway. JAK2 siRNA can inhibit the JAK2/STAT3 signaling mediated by Rhein. The addition of Rhein can significantly increase the activity of mitochondrial superoxide dismutase (SOD) and reduce the MDA, which indicates that the oxidative damage of mitochondria induced by Rhein was significantly weakened. The mitochondrial functional changes induced by Rhein can be reversed by JAK2 siRNA. Conclusion: Our study shows that Rhein can reduce ROS in cardiomyocytes by JAK2/STAT3 signaling pathway activation, and effectively inhibit the apoptosis of cardiomyocytes, thus having a direct protective effect on cardiomyocytes under SIR.

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