Dexmedetomidine protects mice against myocardium ischaemic/reperfusion injury by activating an AMPK/PI3K/Akt/eNOS pathway

Sun, Yanjun; Jiang, Chuan; Jiang, Jun; Qiu, Lisheng

doi:10.1111/1440-1681.12791

Cited by 53 publications

(47 citation statements)

References 36 publications

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“…It attenuates sympathetic tone, with reduction of the neuroendocrine and hemodynamic responses to anesthesia and surgery; decrease opioid and anesthetic requirements; and causes sedation without risk of respiratory depression. Many reports have noted other possible applications including use as a protective agent against ischemia/ reperfusion (I/R) injury in various organs [10,11], including heart [12], kidney [13], brain [14], lung [15], liver [16], and even retina [17]. Only three studies have addressed the roles of miRNAs in mechanisms of organ protection [14,18,19].…”

Section: Rongbi Liangmentioning

confidence: 99%

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Yang

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Circulating miRNAs could serve as biomarkers for diagnosis or prognosis of heart diseases and cerebrovascular diseases. Dexmedetomidine has protective effects in various organs. The effects of dexmedetomidine on circulating miRNAs remain unknown. Here, we investigated differentially expressed miRNA and to predict the target genes of the miRNA in patients receiving dexmedetomidine. Methods: The expression levels of circulating miRNAs of 3 patients were determined through high through-put miRNA sequencing technology. Target genes of the identified differentially expressed miRNAs were predicted using TargetScan 7.1 and miRDB v.5. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional annotation and pathway enrichment analysis of target genes respectively. Results: Twelve differentially expressed miRNAs were identified. Five miRNAs were upregulated (hsa-miR-4508, hsa-miR-novel-chr8_87373, hsa-miR-30a-3p, hsa-miR-novel-chr16_26099, hsa-miR-4306) and seven miRNAs (hsa-miR-744-5p, hsa-miR-320a, hsa-miR-novel-chr9_90035, hsa-miR-101-3p, hsa-miR-150-5p, hsa-miR-342-3p, and hsa-miR-140-3p) were downregulated after administration of dexmedetomidine in the subjects. The target genes and pathways related to the differentially expressed miRNAs were predicted and analyzed. Conclusion: The differentially expressed miRNAs may be involved in the mechanisms of action of dexmedetomidine. Specific miRNAs, such as hsa-miR-101-3p, hsa-miR-150-5p and hsa-miR-140-3p, are new potential targets for further functional studies of dexmedetomidine.

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Section: Rongbi Liangmentioning

confidence: 99%

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Yang

Chen

et al. 2018

Cell Physiol Biochem

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“…9,10,15 This protection was conferred through multiple signalling molecules and pathways, including NF-κB, ERK1/2, Nrf2, JAK2/STAT3 and p38/NO, all of which are directly or indirectly regulated by α 2 -AR. However, a high concentration (50 nM) of Dex conversely promoted DDP-induced toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…9,10 Protection by Dex appears to be primarily dependant on α 2 -adrenergic activation, as blocking the α 2 -AR abolishes these protective effects. Dex is popular not only for its synergistic anaesthetic effect with other anaesthetics, but also for the strong protection against tissue injury and function impairment it provides.…”

Section: Introductionmentioning

confidence: 99%

“…Dex is popular not only for its synergistic anaesthetic effect with other anaesthetics, but also for the strong protection against tissue injury and function impairment it provides. 9,10 Protection by Dex appears to be primarily dependant on α 2 -adrenergic activation, as blocking the α 2 -AR abolishes these protective effects. 11 α 2 -AR is a G i -type G proteincoupled receptor that reduces intracellular cyclic AMP (cAMP) levels.…”

Section: Introductionmentioning

confidence: 99%

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Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

Yang

Chen

Yan

et al. 2019

J of Cellular Biochemistry

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With the extensive use of dexmedetomidine (Dex) in the surgical resection of tumours for its potent sedative and analgesic properties, its effects on various properties of tumours have received increased attention. The study described herein aimed to investigate the effects of Dex on glioma cells in the presence or absence of cisplatin (DDP). Glioma U251 and U87MG cells were treated with different doses (1‐50 nM) of Dex for 12 hours, then recultured in a Dex‐free medium. In addition, Dex was added to U251 and U87MG cells 12 hours before or simultaneously with a 12‐hour DDP treatment. Treatment with Dex increased the viability of both cell lines; this effect continued for at least 24 hours after Dex was removed. A cell invasion assay indicated that Dex inhibited cell invasion at 50 nM, but not at 10 nM. Western blot analysis showed that Dex increased the expression of phosphorylated extracellular‐signal‐regulated kinase 1/2, phosphoitide 3‐kinase and p‐AKT, but decreased ROCK protein levels at a dose of 50 nM. Intracellular Ca 2+ concentration was decreased by Dex in a dose‐dependent manner. DDP toxicity was attenuated by 10 nM Dex added either before or with DDP treatment. However, pretreatment with 50 nM Dex instead enhanced the toxicity of DDP. Single‐dose treatment with Dex did not significantly change glioma volume in nude mice, but changed the expression of Ki67 and matrix metalloproteinase‐3 in the tumour. In conclusion, this study provides evidence of the regulatory effects of Dex on proliferation, invasion and chemosensitivity of glioma cells, and outlines potential mechanisms for these effects.

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“…NO generated by catalysis of eNOS can relax the blood vessels, reduce the cardiac preload and afterload which lead to myocardial protection (19). It can also directly enhance the dilatation effect of ventricular muscle, maintain cardiac output through the left ventricle Frank-Starling regulation mechanism and be beneficial for the heart pump function under physiological and pathological states (20).…”

Section: Discussionmentioning

confidence: 99%

Analysis on mechanism of ATP-sensitive K+ channel opener natakalim improving congestive heart failure after myocardial infarction

Feng

2016

Experimental and Therapeutic Medicine

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The action mechanism of natakalim, a novel ATP-sensitive potassium channel opener, was studied in ameliorating the congestive heart failure (CHF) after myocardial infarction. A total of 25 healthy Wistar male rats (age, 10 weeks; average weight, 300 g) were selected, and the CHF models after acute myocardial infarction (AMI) were prepared by ligation of left anterior descending branch. They were randomly divided into the sham operation group, the model group and the groups of 1, 3 and 9 mg/kg/day natakalims. Each group had 5 mice that were sacrificed after 8 weeks. We compared left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), left ventricular mass index, myocardial cell cross-sectional area, myocardial collagen content, plasma endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) levels. Compared with the sham operation, the LVEDD and NT-proBNP in the model group and each natakalim group were elevated. LVEF decreased significantly, while the left ventricular mass index, myocardial cell cross-sectional area, myocardial collagen content, plasma ET-1 and eNOS levels increased. Natakalim intervention improved the above changes and the improvement effect of 3 mg/kg/day group was the highest. The mechanism of natakalim against the endothelin system can be explained by the fact that inhibiting ET-1 synthesis can reduce the ET-1 levels in circulation leading to the release of NO and PGI2. Inhibition of the vasoconstriction effect of ET-1 can improve the hemodynamics of high-load status and ameliorate the cardiac systolic and diastolic functions. In conclusion, natakalim can improve the ventricular remodeling of CHF after AMI, and 3 mg/kg/day was the most effective dose.

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Dexmedetomidine protects mice against myocardium ischaemic/reperfusion injury by activating an AMPK/PI3K/Akt/eNOS pathway

Cited by 53 publications

References 36 publications

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

Analysis on mechanism of ATP-sensitive K+ channel opener natakalim improving congestive heart failure after myocardial infarction

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