Dexmedetomidine ameliorates LPS induced acute lung injury via GSK-3β/STAT3-NF-κB signaling pathway in rats

Zhang, Huayun; Sha, Jichen; Feng, Xiujing; Hu, Xueyuan; Chen, Yongping; Li, Bei; Fan, Honggang

doi:10.1016/j.intimp.2019.105717

Cited by 58 publications

(47 citation statements)

References 51 publications

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“…These conclusions were similar in our study, in which the first time of diagnosis of PPCs was 4 (2 to 5) days in DEX group and 3 (2 to 5) days in control group. We assumed that DEX infusion could alleviate the lung injury during the infusion time by reducing inflammation and stress, as well as protecting the immune function 35 . But the effects of DEX on clinical outcomes, such as PPCs, would gradually emerge after DEX termination.…”

Section: Discussionmentioning

confidence: 99%

“…Various studies had showed that DEX could suppress systemic inflammatory processes by downregulation the signaling pathway of HMGB1-TLR4-MyD88-MARK-NF-κB and inflammatory mediators of IL-1, IL-4, IL-6, IL-8 and TNF-α, etc. 35,39 by activating α 2 adrenergic receptors and stimulating the vagus nerve via a vagal and α 7 nicotinic acetylcholine receptor-dependent mechanism 40 . Fourth, DEX had been demonstrated to have lung protective effects by reducing dead space ventilation, increasing dynamic compliance 13 , so this point also might be one of the reasons why DEX could decrease PPCs in our study.…”

Section: Discussionmentioning

confidence: 99%

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Dexmedetomidine for prevention of postoperative pulmonary complications in patients after oral and maxillofacial surgery with fibular free flap reconstruction:a prospective, double-blind, randomized, placebo-controlled trial

Liu

Zhu²,

Zhou

et al. 2020

Preprint

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Background: Postoperative pulmonary complications (PPCs) are common and significant problems for oral and maxillofacial surgery patients. Dexmedetomidine (DEX), an α2-adrenoreceptor agonist, has been proven having lung protection effects. However, since now, there has not been final conclusion about whether DEX can reduce the incidence of PPCs. We hypothesize that, in oral and maxillofacial surgery with fibular free flap reconstruction patients, DEX may decrease the incidence of PPCs.Methods: This was a prospective, double-blind, randomized, placebo-controlled, single-centered trial with two parallel arms. A total of 160 patients at intermediate-to-high risk of PPCs undergoing oral and maxillofacial surgery with fibular free flap reconstruction and tracheotomy were enrolled and randomized to receive continuous infusion of either DEX or placebo (normal saline). 0.4 ug/kg of DEX was given over 10mins as an initial dose followed by a maintaining dose of 0.4 ug/kg/h till the second day morning after surgery. At the same time, the normal saline was administered a similar quantity. The primary outcome was the incidence of PPCs according to Clavien-Dindo score within 7 days after surgery. Results: The two groups had similar characteristics at baseline. 18(22.5%) of 80 patients administered DEX, and 32(40.0%) of 80 patient administered placebo experienced PPCs within the first 7 days after surgery (relative risk [RR] 0.563,95% confidence interval [CI] 0.346-0.916; P=0.017). In the first 7 days after surgery, the DEX group had a lower incidence of PPCs and a better postoperative survival probability (Log-rank test, P=0.019), and was less prone to occur PPCs (Cox regression, P=0.025, HR=0.516). When the total dose of DEX was more than 328μg, the patients were unlikely to have PPCs (ROC curve, AUC=0.614, P=0.009).Conclusions: For patients undergoing oral and maxillofacial surgery with fibular free flap reconstruction and tracheotomy who were at intermediate or high risk of developing PPCs, continuous infusion of DEX could decrease the occurrence of PPCs during the first 7 days after surgery and shorten the length of hospital stay after surgery, but did not increase the prevalence of bradycardia or hypotension. Trial registration: Chinese Clinical Trial Registry, www.chictr.org.cn, number: ChiCTR1800016153; Registered on May 15, 2018.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine for prevention of postoperative pulmonary complications in patients after oral and maxillofacial surgery with fibular free flap reconstruction:a prospective, double-blind, randomized, placebo-controlled trial

Liu

Zhu²,

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Various studies had showed that DEX could suppress systemic inflammatory processes by downregulation the signaling pathway of HMGB1-TLR4-MyD88-MARK-NF-κB and inflammatory mediators of IL-1, IL-4, IL-6, IL-8 and TNF-α, etc. 30,31 by activating α 2 adrenergic receptors and stimulating the vagus nerve via a vagal and α 7 nicotinic acetylcholine receptordependent mechanism 32 . Fourth, DEX had been demonstrated to have lung protective effects by reducing dead space ventilation, increasing dynamic compliance 12 , so this point also might be one of the reasons why DEX could decrease PPCs in our study.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine for prevention of postoperative pulmonary complications in patients after oral and maxillofacial surgery with fibular free flap reconstruction: a prospective, double-blind, randomized, placebo-controlled trial

Liu

Zhu²,

Zhou

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Postoperative pulmonary complications (PPCs) are common and significant problems for oral and maxillofacial surgery patients. Dexmedetomidine (DEX), an α2-adrenoreceptor agonist, has been proven having lung protection effects. However, since now, there has not been final conclusion about whether DEX can reduce the incidence of PPCs. We hypothesize that, in oral and maxillofacial surgery with fibular free flap reconstruction patients, DEX may decrease the incidence of PPCs.Methods: This was a prospective, double-blind, randomized, placebo-controlled, single-centered trial with two parallel arms. A total of 160 patients at intermediate-to-high risk of PPCs undergoing oral and maxillofacial surgery with fibular free flap reconstruction and tracheotomy were enrolled and randomized to receive continuous infusion of either DEX or placebo (normal saline). 0.4ug/kg dose of DEX was given over 10mins as an initial dose followed by a maintaining dose of 0.4ug/kg/h till the second day morning after surgery. At the same time, the normal saline was administered a similar quantity. The primary outcome was the incidence of PPCs according to Clavien-Dindo score within 7 days after surgery.Results: The two groups had similar characteristics at baseline. 18(22.5%) of 80 patients administered DEX, and 32(40.0%) of 80 patient administered placebo experienced PPCs within the first 7 days after surgery (relative ratio [RR] 0.563,95% confidence interval [CI] 0.346-0.916; P=0.017). In the first 7 days after surgery, the DEX group had a lower incidence of PPCs and a better postoperative survival probability (Log-rank test, P=0.019), and was less prone to occur PPCs (Cox regression, P=0.025, HR=0.516). When the total dose of DEX was more than 328μg, the patients were unlikely to have PPCs (ROC curve, AUC=0.614, P=0.009).Conclusions: Continuous infusion of DEX marks a huge decrease in the appearance of PPCs within the first 7days after surgery, for patients undergoing oral and maxillofacial surgery with fibular free flap reconstruction and tracheotomy.Trial registration: Chinese Clinical Trial Registry, www.chictr.org.cn, number: ChiCTR1800016153; Registered on May 15, 2018.

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“…A good anti-in ammatory effect of DEX has been discovered on important organs in mice with spinal cord injury, myocardial ischemia-reperfusion and sepsis, etc. [7]. Moreover, DEX can improve ARDS, reduce pathomorphological changes, inhibit oxidative stress damage, in ammatory response and apoptosis in lung epithelial cells by inhibiting TLR-4/NF-κB pathway [8].…”

Section: Introductionmentioning

confidence: 99%

miR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14

Ding

Gao

et al. 2020

Preprint

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Background: To investigate the mechanism of miR-128-3p and MAPK14 on the protective effect of dexmedetomidine on acute lung injury in septic mice.Methods: SPF C57BL/6 mice were divided into 8 groups. The pathological changes and wet/dry weight ratio (W/D), PaO2, PaCO2, MDA, SOD and MPO levels in lung tissue and the serum levels of inflammation factors were observed. Dual luciferase reporter assay was used to verify the targeting relationship between miR-128-3p and MAPK14. qPCR and WB were used to detect the expression of miR-128-3p and MAPK14.Results: Compared with the Normal group, other groups had lower MDA, MPO, inflammatory factors levels and the expression level of MAPK14, while the content of SOD and the expression level of miR-128-3p was significantly decreased. DEX treatment and up-regulation of miR-128-3p could significantly decrease the contents of MDA, MPO, inflammatory factor levels and significantly increase the SOD content in model mice, however, MAPK14 over-expression had opposite effects. miR-128-3p up-regulation enhanced the changes of above indicators caused by DEX treatment and MAPK14 over-expression could block the protective effect of DEX on acute lung injury in septic mice. miR-128-3p up-regulation reversed the effects of MAPK14 over-expression in model mice.Conclusion: miR-128-3p can further enhance the protective effect of dexmedetomidine on acute lung injury in septic mice by targeting and inhibiting MAPK14 expression.

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Dexmedetomidine ameliorates LPS induced acute lung injury via GSK-3β/STAT3-NF-κB signaling pathway in rats

Cited by 58 publications

References 51 publications

Dexmedetomidine for prevention of postoperative pulmonary complications in patients after oral and maxillofacial surgery with fibular free flap reconstruction:a prospective, double-blind, randomized, placebo-controlled trial

Dexmedetomidine for prevention of postoperative pulmonary complications in patients after oral and maxillofacial surgery with fibular free flap reconstruction:a prospective, double-blind, randomized, placebo-controlled trial

Dexmedetomidine for prevention of postoperative pulmonary complications in patients after oral and maxillofacial surgery with fibular free flap reconstruction: a prospective, double-blind, randomized, placebo-controlled trial

miR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14

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