Dexmedetomidine alleviates lipopolysaccharide-induced lung injury in Wistar rats

Yan, Xuetao; Cheng, Xiaoli; Zhou, Liwen; He, Xiang-Hu; Zheng, Wenzhong; Hu, Chen

doi:10.18632/oncotarget.17899

Cited by 14 publications

(11 citation statements)

References 29 publications

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“…Previous studies demonstrate that Dex exhibit potential in vitro and in vivo anti-inflammatory activity 20 , 21 , suggesting its potential in ameliorating inflammation induced by diabetes. Inflammatory cytokines play an important role in neuronal damage, especially in painful neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain

et al. 2019

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Purpose:To evaluate the effects of Dexmedetomidine (Dex) on spinal pathology and inflammatory factor in a rat model of Diabetic neuropathic pain (DNP).Methods:The rats were divided into 3 groups (eight in each group): normal group (N group), diabetic neuropathic pain model group (DNP group), and DNP model with dexmedetomidine (Dex group). The rat model of diabetes was established with intraperitoneal streptozotocin (STZ) injections. Nerve cell ultrastructure was evaluated with transmission electron microscopy (TEM). The mechanical withdrawal threshold (MWT) and motor nerve conduction velocity (MNCV) tests documented that DNP rat model was characterized by a decreased pain threshold and nerve conduction velocity.Results:Dex restored the phenotype of neurocytes, reduced the extent of demyelination and improved MWT and MNCV of DNP-treated rats (P=0.01, P=0.038, respectively). The expression of three pain-and inflammation-associated factors (P2X4, NLRP3, and IL-IP) was significantly upregulated at the protein level in DNP rats, and this change was reversed by Dex administration (P=0.0022, P=0.0092, P=0.0028, respectively).Conclusion:The P2X4/NLRP3 signaling pathway is implicated in the development and presence of DNP in vivo, and Dex protects from this disorder.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain

et al. 2019

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“…51 Furthermore, dexmedetomidine is reported to alleviate LPS-induced lung injury in Wistar rats via the Nrf2/Keap1 pathway. 52 Whether or not dexmedetomidine functions via the Nrf2/Keap1 pathway in LPS-induced neuronal damage should be further clarified in our future study. Rui et al reported that miR-410 had neuroprotective effects against sevoflurane-induced cognitive dysfunction in rats via activation of the PI3K/AKT pathway.…”

Section: Discussionmentioning

confidence: 91%

Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons

Zeng¹,

Zhang²,

Long³

et al. 2021

NDT

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Objective Dexmedetomidine, an α2-adrenergic receptor agonist, mitigates cognitive dysfunction in elderly patients after surgery with general anesthesia. However, the underlying mechanism by which dexmedetomidine reduces cognitive dysfunction remains to be fully elucidated. The aim of this study was to investigate the effects of dexmedetomidine on lipopolysaccharide (LPS)-induced neuronal dysfunction in cultured hippocampal neurons. Methods LPS, in the presence and absence of dexmedetomidine, was applied to cultured hippocampal neurons to mimic post-surgical inflammation. Neuronal morphology, including neurite outgrowth and synaptic transmission, was observed, and miniature excitatory postsynaptic currents were recorded by electrophysiological patch-clamp. Results LPS significantly impaired neurite outgrowth in hippocampal neurons in a concentration- and time-dependent manner, which was reversed by dexmedetomidine treatment. Electrophysiological patch-clamp results showed that LPS induced synaptic transmission dysfunction, which was restored after dexmedetomidine addition. Furthermore, Western blotting assays showed that LPS suppressed the AKT/GSK-3β/CRMP-2 signaling pathway and dexmedetomidine countered the inhibitory effect of LPS by re-activating this pathway. Conclusion In general, dexmedetomidine protected against the effects of LPS-induced hippocampal neuron damage, including neurite outgrowth and synaptic transmission. Overall, dexmedetomidine modulated the AKT/GSK-3β/CRMP-2 signaling pathway to alleviate LPS-induced neurological dysfunction.

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“…DEX has been shown to have a beneficial effect on acute lung injury [29]. Hu and colleagues observed that DEX can mitigate CLP-stimulated ALI, and potentially through the reduced the activation of NF-κB and MAPK [24].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Dexmedetomidine on Acute Lung Injury via the Upregulation of Tumour Necrosis Factor-α-Induced Protein-8-like 2 in Septic Mice

Kong

Qiu

et al. 2020

Inflammation

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The aim of the present study was to investigate whether TIPE2 participates in the protective actions of dexmedetomidine (DEX) in a mouse model of sepsis-induced acute lung injury (ALI). We administered TIPE2 adeno-associated virus (AAV-TIPE2) intratracheally into the lungs of mice. Control mice were infected with an adeno-associated virus expressing no transgene. Three weeks later, an animal model of caecal ligation-perforation (CLP)-induced sepsis was established. DEX was administered intravenously 30 min after CLP. Twenty-four hours after sepsis, lung injury was assayed by lung histology, the ratio of polymorphonuclear leukocytes (PMNs) to total cells in the bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activity, BALF protein content and the lung wet-to-dry (W/D) weight ratio. Proinflammatory factor levels in the BALF of mice were measured. The protein expression levels in lung tissues were analysed by Western blotting. The results showed that DEX treatment markedly mitigated sepsis-induced lung injury, which was characterized by the deterioration of histopathology, histologic scores, the W/D weight ratio and total protein levels in the BALF. Moreover, DEX markedly attenuated sepsis-induced lung inflammation, as evidenced by the decrease in the number of PMNs in the BALF, lung MPO activity and proinflammatory cytokines in the BALF. In addition, DEX dramatically prevented sepsis-induced pulmonary cell apoptosis in mice, as reflected by decreases in the number of TUNEL-positive cells, the protein expression of cleaved caspase-9 and cleaved caspase 3 and the Bax/Bcl-2 ratio. In addition, evaluation of protein expression showed that DEX blocked sepsis-activated JNK phosphorylation and NF-κB p65 nuclear translocation. Similar results were also observed in the TIPE2 overexpression group. Our study demonstrated that DEX inhibits acute inflammation and apoptosis in a murine model of sepsis-stimulated ALI via the upregulation of TIPE2 and the suppression of the activation of the NF-κB and JNK signalling pathways.KEY WORDS: acute lung injury; TIPE2; dexmedetomidine; apoptosis; inflammation.Qian Kong and Xiaojing Wu contributed equally to this work.

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Dexmedetomidine alleviates lipopolysaccharide-induced lung injury in Wistar rats

Cited by 14 publications

References 29 publications

Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain

Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain

Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons

Protective Effect of Dexmedetomidine on Acute Lung Injury via the Upregulation of Tumour Necrosis Factor-α-Induced Protein-8-like 2 in Septic Mice

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