Dexmedetomidine alleviates non-ventilation associated lung injury via modulating immunology phenotypes of macrophages

Shen, Qiying; Xu, Gaowei; Liu, Jing; Wang, Lixia; Zhou, Yixin; Yu, Yonghao; Lv, Changming; Liu, Xuesheng

doi:10.1016/j.lfs.2020.118249

Cited by 12 publications

(6 citation statements)

References 25 publications

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“…Of the 1218 potential articles in the initial search, 20 RCTs 24–43 met the inclusion criteria. The screening and selection process is demonstrated in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Of the 1218 potential articles in the initial search, 20 RCTs 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 met the inclusion criteria. The screening and selection process is demonstrated in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Seven trials 27 , 31 , 32 , 34 , 37 , 38 , 39 evaluated the effect dexmedetomidine had on oxygenation at 30 min after OLV. As shown in Figure S2 , significant increases were observed of both PaO 2 and oxygen index in the dexmedetomidine group [PaO 2 : MD, 8.55, 95%CI (0.79, 16.30), p < 0.00001; OI: MD, 61.90, 95%CI (43.78, 80.01)], p < 0.00001)].…”

Section: Resultsmentioning

confidence: 99%

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Dexmedetomidine attenuates one‐lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta‐analysis

Bai

Zhang

Zhao

et al. 2021

Clin Exp Pharma Physio

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One‐lung ventilation (OLV), a common ventilation technique, is associated with perioperative lung injury, tightly connected with inflammatory responses. Dexmedetomidine has shown positive anti‐inflammatory effects in lung tissues in pre‐clinical models. This study investigated the efficacy of dexmedetomidine for suppressing inflammatory responses in patients requiring OLV. We searched PubMed, MEDLINE, Embase, Scopus, Ovid, and Cochrane Library for randomized controlled trials focusing on dexmedetomidine’s anti‐inflammatory effects on patients requiring OLV without any limitation on the year of publication or languages. 20 clinical trials were assessed with 870 patients in the dexmedetomidine group and 844 in the control group. Our meta‐analysis investigated the anti‐inflammatory property of dexmedetomidine perioperatively [T1 (30‐min OLV), T2 (90‐min OLV), T3 (end of surgery) and T4 (postoperative day 1)], demonstrating that dexmedetomidine’s intraoperative administration resulted in a significant reduction in serum concentration of interleukin‐6, tumor necrosis factor‐α and other inflammatory cytokines perioperatively. By calculating specific I2 index, significant heterogeneity was observed on all occasions, with I2 index ranging from 95% to 99%. For IL‐6 changes, sensitivity analysis showed that the exclusion of a single study led to a significant decrease of heterogeneity (96%–0%; p < 0.00001). Besides, pulmonary oxygenation was ameliorated in the dexmedetomidine group comparing with the control group. In conclusion, perioperative administration of dexmedetomidine can attenuate OLV induced inflammation, ameliorate pulmonary oxygenation, and may be conducive to a decreased occurrence of postoperative complications and better prognosis. However, the results should be prudently interpreted due to the evidence of heterogeneity and the limited number of studies.

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“…Of the 1218 potential articles in the initial search, 20 RCTs 24–43 met the inclusion criteria. The screening and selection process is demonstrated in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Dexmedetomidine attenuates one‐lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta‐analysis

Bai

Zhang

Zhao

et al. 2021

Clin Exp Pharma Physio

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“…Currently, dexmedetomidine is one of the most widely used anaesthetic agents in the perioperative period and in the ICU. Dexmedetomidine has been widely reported to reduce ventilator-induced lung injury by activating the ERK1/2 pathway [7] and to reduce non-ventilator-related lung injury by modulating the immune phenotype of macrophages [22] ; it can also improve endotoxin-induced acute lung injury in vivo by maintaining mitochondrial dynamic homeostasis through the HIF-1a/HO-1 signalling pathway [8] ; it has also been related demonstrated its effectiveness in chronic obstructive pulmonary disease [23] . In the present study, dexmedetomidine was shown to attenuate airway resistance in an OVA-induced asthma model, and its protective effect on the lung was again con rmed by sectioning and staining of lung tissue.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TLR4/NF-κ Signaling Pathway to Alleviate Airway hyperresponsiveness in OVA Mice

Zhi¹,

Duan²,

Wang³

et al. 2021

Preprint

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Background: Asthma is a disease that affects health worldwide. It is characterised by inflammation and airway hyperreactivity. Because airway hyperreactivity can occur in other diseases, perioperative airway hyperreactivity is more insidious and widespread than in asthma and has serious implications that need to be addressed urgently. The use of dexmedetomidine in acute asthma and lung protection has been reported, but the exact mechanism is unclear. Objective: To investigate the effectiveness and mechanisms associated with dexmedetomidine in airway hyperresponsiveness.Methods: Forty BALB/c female mice were randomly divided into five groups: group K (blank group), group A (asthma group), group HD (asthma + dexmedetomidine treatment group), group TH (asthma + yohimbine group) and group HT (asthma + dexmedetomidine + yohimbine group), and the airway resistance of group K, group A and group HD were analysed by invasive airway resistance assay, ELISA assay, immunohistochemistry and q-PCR, respectively. Airway resistance; IL-4 and IgE levels in serum and BLAF; and IL-4, IL-13, Muc5AC, NFκB, TLR2, TLR4 and TSLP1 protein levels in lung tissues of the 5 groups were analysed by invasive airway resistance assay, ELISA, immunohistochemistry and qPCR. RESULTS: Compared with group A, there were statistical differences in airway resistance (P < 0.05); LIL-4 and IgE (P < 0.05) in serum and BLAF; and Muc5AC, TLR4 and NFκB protein contents (P < 0.05) in lung tissues in the HD group. Conclusion: 1. Dexmedetomidine can attenuate airway hyperresponsiveness in the OVA asthma model; 2. Dexmedetomidine reduced the production of IL-4 and IgE by down-regulating the TLR4/NF-κB signaling pathway, thereby reducing the lung inflammatory response and airway hyperresponsiveness in the OVA-induced asthma model.

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“…Subsequently, the sections were stained with hematoxylin and eosin (H&E), and light microscopy was used to examine the sections. Finally, the lung injury scores were determined using a semiquantitative method as described previously (Shen et al, 2020). Lung tissue sections (5 μm) were procedurally dewaxed, hydrated, and incubated in 3% H 2 O 2 for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Abscisic acid inhibited reactive oxygen species‐mediated endoplasmic reticulum stress by regulating the PPAR‐γ signaling pathway in ARDS mice

Wang

Zou

Xiao

et al. 2021

Phytotherapy Research

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Acute respiratory distress syndrome (ARDS) is a life‐threatening form of a respiratory disorder, and there are few effective therapies. Abscisic acid (ABA) has been proven to be effective in influenza and asthma. Herein, we explored the protective effect of ABA on the resolution of ARDS and the underlying mechanism. Mice were challenged with lipopolysaccharide (LPS) to establish an ARDS model. We found that ABA reduced pulmonary injury, with concomitant suppression of endoplasmic reticulum (ER) stress and reduction of reactive oxygen species (ROS) production. Furthermore, after the elimination of ROS by the specific inhibitor N‐acetyl‐L‐cysteine (NAC), ABA did not further inhibit airway inflammation or ER stress in ARDS mice. In addition, ABA inhibited ROS production through nuclear factor erythroid 2–related factor 2 (Nrf2) activation in parallel with elevated levels of peroxisome proliferator activated receptor γ (PPAR‐γ). Furthermore, the addition of a PPAR‐γ antagonist abrogated the suppressive action of ABA on inflammation as well as on ER stress and oxidative stress, while NAC restored the protective effect of ABA in ARDS mice treated with a PPAR‐γ antagonist. Collectively, ABA protects against LPS‐induced lung injury through PPAR‐γ signaling, and this effect may be associated with its inhibitory effect on ROS‐mediated ER stress.

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Dexmedetomidine alleviates non-ventilation associated lung injury via modulating immunology phenotypes of macrophages

Cited by 12 publications

References 25 publications

Dexmedetomidine attenuates one‐lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta‐analysis

Dexmedetomidine attenuates one‐lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta‐analysis

Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TLR4/NF-κ Signaling Pathway to Alleviate Airway hyperresponsiveness in OVA Mice

Abscisic acid inhibited reactive oxygen species‐mediated endoplasmic reticulum stress by regulating the PPAR‐γ signaling pathway in ARDS mice

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