Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury: An in vivo and in vitro study

Chen, Lingyang; Cao, Jianbin; Cao, Donghang; Wang, Mingcang; Hai-fei, Xiang; Yang, Yanqing; Ying, Tingting; Cong, Haitao

doi:10.1016/j.lfs.2019.116553

Cited by 46 publications

(31 citation statements)

References 43 publications

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“…A previous study suggested that SIRT1 is involved in biological processes such as apoptosis, stress resistance and energy balance in ischemic injury in the heart and cardiometabolic diseases [15]. Through the involvement of SIRT1, Dex attenuates cerebral I/R by weakening oxidative stress, apoptosis and inflammation [16]. mTOR is a serine/threonine kinase that modulates a number of processes related to cellular growth, including metabolism and differentiation [17].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine postconditioning suppresses myocardial ischemia/reperfusion injury by activating the SIRT1/mTOR axis

Zhang

Wang

et al. 2020

Bioscience Reports

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Myocardial ischemia/reperfusion (MI/R) triggers a complicated chain of inflammatory reactions. Dexmedetomidine (Dex) has been reported to be important in myocardial disorders. We evaluated the role of Dex in MI/R injury via the silent information regulator factor 2-related enzyme 1 (SIRT1)/mammalian target of rapamycin (mTOR) signaling pathway. First, Dex was immediately injected into rat models of MI/R injury during reperfusion. After Evans Blue-triphenyl tetrazolium chloride (TTC) and Hematoxylin–Eosin (H-E) staining, MI/R injury was observed. The extracted serum and myocardial tissues were used to detect oxidative stress and the inflammatory response. Western blot analysis was performed to evaluate MI/R autophagy and the levels of proteins associated with the SIRT1/mTOR axis. The effects of the combination of Dex and SIRT1 inhibitor EX527 on MI/R injury and autophagy were evaluated. Finally, the mechanism of Dex was tested, and autophagy levels and the levels of proteins associated with the SIRT1/mTOR signaling pathway were assessed in MI/R rats. The results of the present study suggested that Dex relieved MI/R injury, reduced cardiomyocyte apoptosis, oxidative stress and inflammatory reactions, up-regulated the SIRT1/mTOR axis and decreased overautophagy in MI/R rats. SIRT1 inhibitor EX527 attenuated the protective effects of Dex. Our study demonstrated that Dex alleviated MI/R injury by activating the SIRT1/mTOR axis. This investigation may offer new insight into the treatment of MI/R injury.

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Section: Introductionmentioning

confidence: 99%

Dexmedetomidine postconditioning suppresses myocardial ischemia/reperfusion injury by activating the SIRT1/mTOR axis

Zhang

Wang

et al. 2020

Bioscience Reports

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“…A large number of studies have confirmed that the main mechanism of reperfusion injury is oxidative stress injury caused by excessive production of free radicals and direct cell injury caused by intracellular calcium overload, along with some other potential causes, such as inflammation, microvascular injury, and endothelial dysfunction. Among these factors, oxidative stress and apoptosis play important roles in I/R injury of AMI . In the early stage of I/R injury of MI, we analysed and identified hundreds of differentially expressed lncRNAs based on previous microarray analysis .…”

Section: Discussionmentioning

confidence: 99%

“…Among these factors, oxidative stress and apoptosis play important roles in I/R injury of AMI. 5,7,21 In the early stage of I/R injury of MI, we analysed and identified hundreds of differentially expressed lncRNAs based on previous microarray analysis. 15 The highly expressed and highly conserved lncRNA Gpr19 attracted our attention.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the LncRNA Gpr19 attenuates ischemia‐reperfusion injury after acute myocardial infarction by inhibiting apoptosis and oxidative stress via the miR‐324‐5p/Mtfr1 axis

et al. 2019

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Reperfusion therapy after acute myocardial infarction (AMI) can effectively restore the blood supply and nutritional support of ischemic myocardium and save the dying myocardium. However, myocardial ischaemia‐reperfusion (I/R) injury has become a new threat to reperfusion therapy for AMI. Many long‐chain noncoding RNAs (lncRNAs) are dysregulated by I/R damage. Of these dysregulated lncRNAs, Gpr19 was selected as a potential gene of interest based on its high expression change. We aimed to explore the functional role and molecular mechanism of Gpr19 in I/R injury of AMI. C57BL/6 mice underwent I/R injury as in vivo models. Neonatal rat ventricular cardiomyocytes (NRCMs) exposed to an oxygen glucose deprivation/recovery (OGD/R) system were used as an in vitro model. A TUNEL assay, western blot, and oxidative stress analysis were conducted in this study to determine apoptosis and oxidative stress levels. Our results indicated that inhibition of Gpr19 improves cardiac function and reduces apoptosis and myocardial fibrosis scar formation in vivo. Suppression of Gpr19 attenuates oxidative stress and apoptosis in NRCMs exposed to OGD/R. We further demonstrated that inhibition of Gpr19 decreases oxidative stress and apoptosis in OGD/R‐induced NRCMs by regulating miR‐324‐5p and mitochondrial fission regulator 1 (Mtfr1). We elucidated the functional role and potential molecular mechanism of Gpr19 in I/R injury of AMI, provided a theoretical basis for the importance of Gpr9 in I/R injury, and provided a new perspective for the clinical treatment of I/R injury of AMI.

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“…Despite their protective and regenerative potential, overwhelming hyperglycemia and neuroinflammation have been implicated in the pathogenesis of stroke. Rodent studies have also revealed the crosstalk among tPA, hyperglycemia, and neuroinflammation in cerebral ischemic brain injury, and the existing therapeutic benefits by means of targeting hyperglycemia and neuroinflammation [6][7][8][9][10]. These phenomena underscore the importance of exploring the underlying mechanisms of stroke-accompanied hyperglycemia and neuroinflammation, as well as highlighting their therapeutic potential towards combating stroke disease and related complications.…”

Section: Introductionmentioning

confidence: 96%

Effects of β-Adrenergic Blockade on Metabolic and Inflammatory Responses in a Rat Model of Ischemic Stroke

Lin

Wang

Chang

et al. 2020

Cells

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Ischemic stroke provokes an inflammatory response concurrent with both sympathetic nervous system activation and hyperglycemia. Currently, their crosstalk and consequences in stroke outcomes are of clinical attraction. We have provided experimental evidence showing the suppressive effects of the nonselective β-adrenoreceptor antagonist propranolol on hyperglycemia, inflammation, and brain injury in a rat model experiencing cerebral ischemia. Pretreatment with propranolol protected against postischemic brain infarction, edema, and apoptosis. The neuroprotection caused by propranolol was accompanied by a reduction in fasting glucose, fasting insulin, glucose tolerance impairment, plasma C-reactive protein, plasma free fatty acids, plasma corticosterone, brain oxidative stress, and brain inflammation. Pretreatment with insulin alleviated—while glucose augmented—postischemic brain injury and inflammation. Additionally, the impairment of insulin signaling in the gastrocnemius muscles was noted in rats with cerebral ischemia, with propranolol improving the impairment by reducing oxidative stress and tumor necrosis factor-α signaling. The anti-inflammatory effects of propranolol were further demonstrated in isoproterenol-stimulated BV2 and RAW264.7 cells through its ability to decrease cytokine production. Despite their potential benefits, stroke-associated hyperglycemia and inflammation are commonly linked with harmful consequences. Our findings provide new insight into the anti-inflammatory, neuroprotective, and hypoglycemic mechanisms of propranolol in combating neurodegenerative diseases, such as stroke.

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Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury: An in vivo and in vitro study

Cited by 46 publications

References 43 publications

Dexmedetomidine postconditioning suppresses myocardial ischemia/reperfusion injury by activating the SIRT1/mTOR axis

Dexmedetomidine postconditioning suppresses myocardial ischemia/reperfusion injury by activating the SIRT1/mTOR axis

Inhibition of the LncRNA Gpr19 attenuates ischemia‐reperfusion injury after acute myocardial infarction by inhibiting apoptosis and oxidative stress via the miR‐324‐5p/Mtfr1 axis

Effects of β-Adrenergic Blockade on Metabolic and Inflammatory Responses in a Rat Model of Ischemic Stroke

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