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Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TheTLR4/NF-κB Signaling Pathway to Alleviate Airway Hyperresponsiveness in OVA Mice

2022; RELX Group (Netherlands); Linguagem: Inglês

10.2139/ssrn.4049575

1556-5068

Qirui Duan, Juan Zhi, Dong Yang, Qianyu Wang, Xiyu Du,

Pediatric health and respiratory diseases

Background: Asthma is a heterogeneous disease that affects human health. Airway Hyper-Responsiveness(AHR) is a clinical presentation of abnormal tracheal and bronchial sensitivity causing airflow restriction and is the main basis for the diagnosis of asthma. Asthma patients are at high risk for perioperative tracheal and bronchospasm due to AHR, which can lead to hypoxaemia and haemodynamic instability, and in severe cases to life-threatening 'silent lung'. Therefore, it is important to reduce the incidence or intensity of AHR in the perioperative period.Inflammatory and immune responses are key to the development and progression of AHR.Hypothesis/purpose: Based on the immunomodulatory effect of dexmedetomidine(DEX), we hypothesized that Dexmedetomidine(DEX) attenuate the inflammatory by inhibiting the toll-like receptor 4(TLR4)/nuclear factor(NF-κB) signaling pathway could reduce the mechanical ventilation respiratory parameters of ovalbumin-induced allergic airway hyperresponsiveness.Study design: BABL/C mice were divided into control group and OVA group(Ovalbumin induced allergy). Selected OVA mice by treatment of dexmedetomidine 25 µg/kg for 5 days(OVA+DEX group) or dexmedetomidine 25 µg/kg + yohimbine 1 mg/kg for 5 days (OVA+DEX+Yohimbine). After treatment, bronchoalveolar lavage (BAL) and peripheral blood(ELISA) and lung tissue(H&E) were collected for analysis of inflammatory factors, and changes in lung tissue doing associated inflammatory mediators were verified by PCR. In vivo analysis of airway resistance parameters invasive pulmonary function monitoring.Results: Dexmedetomidine downregulated IL-4 and IgE levels by ELISA in BAL and peripheral blood; dexmedetomidine attenuated inflammatory response and mucus secretion by H&E and PAS staining of lung tissue; dexmedetomidine attenuated proximal airway resistance (Parameter Rn) and total respiratory resistance (Parameter Rrs) by invasive pulmonary function monitoring. Effects of dexmedetomidine on IL-4 and IGE are associated with TLR4/NFκB pathway by PCR.Conclusion: Dexmedetomidine reduces the hyperresponsiveness and the airway inflammatory profile, recovering the lung function. This mechanism of action may be related to the TLR4/NFκB signaling pathway