Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits

Sun, Zhixiang; Zhao, Tianyun; Lv, Shaojun; Gao, Ying; Masters, Joe; Weng, Hao

doi:10.1186/s12967-018-1583-7

Cited by 55 publications

(46 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[8][9][10] Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative, anxiolytic, analgesic, and sympatholytic properties. 11,12 Our previous studies showed that DEX use was associated with improved outcomes and reduced mortality in patients undergoing cardiac surgery. 13,14 In a rat myocardial I/R model, DEX administration prior to ischemia (pretreatment) reduced the myocardial infarct size by inhibiting inflammation via the α2-adrenergic receptor activation.…”

Section: Introductionmentioning

confidence: 99%

<p>Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling</p>

Yuan¹,

Meng²,

Ma³

et al. 2019

DDDT

View full text Add to dashboard Cite

Purpose Intracellular calcium ([Ca 2+ ]i) overload is a major cause of cell injury during myocardial ischemia/reperfusion (I/R). Dexmedetomidine (DEX) has been shown to exert anti-inﬂammatory and organ protective effects. This study aimed to investigate whether pretreatment with DEX could protect H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation (OGD/R) injury through regulating the Ca 2+ signaling. Methods H9c2 cardiomyocytes were subjected to OGD for 12 h, followed by 3 h of reoxygenation. DEX was administered 1 h prior to OGD/R. Cell viability, lactate dehydrogenase (LDH) release, level of [Ca 2+ ]i, cell apoptosis, and the expression of 12.6-kd FK506-binding protein/ryanodine receptor 2 (FKBP12.6/RyR2) and caspase-3 were assessed. Results Cells exposed to OGD/R had decreased cell viability, increased LDH release, elevated [Ca 2+ ]i level and apoptosis rate, down-regulated expression of FKBP12.6, and up-regulated expression of phosphorylated-Ser2814-RyR2 and cleaved caspase-3. Pretreatment with DEX significantly blocked the above-mentioned changes, alleviating the OGD/R-induced injury in H9c2 cells. Moreover, knockdown of FKBP12.6 by small interfering RNA abolished the protective effects of DEX. Conclusion This study indicates that DEX pretreatment protects the cardiomyocytes against OGD/R-induced injury by inhibiting [Ca 2+ ]i overload and cell apoptosis via regulating the FKBP12.6/RyR2 signaling. DEX may be used for preventing cardiac I/R injury in the clinical settings.

show abstract

Section: Introductionmentioning

confidence: 99%

<p>Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling</p>

Yuan¹,

Meng²,

Ma³

et al. 2019

DDDT

View full text Add to dashboard Cite

show abstract

“…Neuromotor function of rats is an important criterion for observing SCI and its recovery . Sensory and functional recovery is the most important and direct observation index for SCI treatment . BBB scores and inclined plate tests were used to assess the severity of SCI.…”

Section: Resultsmentioning

confidence: 99%

“…31 Sensory and functional recovery is the most important and direct observation index for SCI treatment. 8 BBB scores and inclined plate tests were used to assess the severity of SCI. The results showed that compared with the SCI group, the BBB score and inclined plate test score of the SCI-RHL group increased significantly F I G U R E 2 RHL improved antioxidant activity in spinal cord tissues after SCI.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis, also known as programmed cell death, is an intrinsic natural physiological process that maintains the stability of various tissues in the human body by eliminating metabolites of dead cells . The mechanism of apoptosis in nerve cells is very complicated . It is suggested that various posttraumatic stimulation signals can induce apoptosis through different pathways …”

Section: Introductionmentioning

confidence: 99%

“…7 The mechanism of apoptosis in nerve cells is very complicated. 8 It is suggested that various posttraumatic stimulation signals can induce apoptosis through different pathways. 1,6 Mitogen-activated protein kinase (MAPK) is a kind of serine/threonine protein kinase that is important signal transducer of cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

Hao

Wang

Daiping

et al. 2019

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

The current study aims to investigate the effect of rhein lysinate (RHL) on neuromotor function in rats with spinal cord injury (SCI) and to explore the underlying mechanism. A total of 63 adult male SD rats were randomly divided into the sham group, SCI group and RHL group (SCI‐RHL group), with 21 rats in each group. Basso Beattie Bresnahan (BBB) scoring and the inclined plate test were used to evaluate the changes in motor function after SCI. Then, superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and malondialdehyde (MDA) contents were quantified. Caspase‐3‐positive cells in spinal cord tissue were detected by immunohistochemical (IHC) staining, and protein expression was detected by Western blots. Here, our data showed that compared with the SCI group, the BBB score and inclined plate test score of the SCI‐RHL group were significantly higher than those of the SCI group 7 days after the RHL intervention. After 7 days of RHL treatment, the activities of SOD and GSH‐Px in the spinal cord increased significantly. At the same time, RHL reduced the MDA content in spinal cord tissue of SCI rats. Moreover, cleaved‐caspase‐3‐positive cells and apoptotic cells were significantly lower in the SCI‐RHL group than in the SCI group. More importantly, p38 mitogen‐activated protein kinase (p38 MAPK) was significantly decreased in the SCI‐RHL group compared with the SCI group. In summary, RHL can inhibit the activation of the p38 MAPK pathway after SCI, thereby reducing the apoptosis of spinal cord neurons and improving the neuromotor function of SCI rats.

show abstract

Dexmedetomidine protects against lung injury induced by limb ischemia‐reperfusion via the TLR4/MyD88/NF‐κB pathway

Xue

Chen

Tang

et al. 2019

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

Dexmedetomidine (DEX) can protect the lung from ischemia-reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. The aims of this study were to determine whether DEX attenuates lung injury following lower extremity I/R and to investigate the related toll-like receptor 4 (TLR4) signaling pathway. Twenty-eight SD rats were divided into four groups (n = 7): Sham, I/R, I/R + DEX (25 μg/kg prior to ischemia), and I/R + DEX + Atip (250 μg/kg atipamezole before DEX treatment). Lower extremity I/R was induced by left femoral artery clamping for 3 hours and followed by 2 hours reperfusion. Quantitative alveolar damage and the wet/dry (W/D) ratio were calculated. Interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)α in the bronchoalveolar lavage fluid (BALF) and serum and myeloperoxidase (MPO) in the lung were measured. The TLR4 and MyD88 mRNA expression levels were measured by RT-PCR, nuclear factor (NF)-κB, and phosphorylated NF-κB by western blot, respectively. Quantitative alveolar damage, W/D ratio, MPO, BALF and serum IL-1, IL-6, and TNF-α, and TLR4, MyD88, NF-κB, and p-NF-κB expression significantly increased in the I/R group relative to the Sham group. DEX preconditioning significantly reduced lung edema, and histological injury relative to the I/R group. Serum and BALF IL-1, IL-6, and TNF-α levels, MPO activity and TLR4, MyD88, NF-κB, and p-NF-κB expression were also significantly reduced in the I/R + DEX group compared with the I/R group. Atipamezole partially reversed all the aforementioned effects. DEX preconditioning protects the lungs against lower extremity I/R injury via α2-adrenoceptor-dependent and α2-adrenoceptor-independent mechanisms. It also suppresses the TLR4 pathway and reduces inflammation. K E Y W O R D S acute lung injury, dexmedetomidine, limb ischemia/reperfusion injury, toll-like receptor 4

show abstract

Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits

Cited by 55 publications

References 37 publications

<p>Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling</p>

<p>Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling</p>

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

Dexmedetomidine protects against lung injury induced by limb ischemia‐reperfusion via the TLR4/MyD88/NF‐κB pathway

Contact Info

Product

Resources

About