Propofol Attenuates Airway Inflammation In A Mast Cell-Dependent Mouse Model Of Allergic Asthma By Inhibiting The Toll-like Receptor4/Reactive Oxygen Species/Nuclear Factor κB Signaling Pathway

ObjectiveAsthma is a chronic respiratory allergic inflammatory disease.The main pathological features of asthma are airway hyperresponsiveness with reversible airflow obstruction,increased airway mucus secretion,and an airway chronic inflammatory response involving inflammatory cells such as eosinophils,mast cells,and T cells.Severe asthma attacks during anaesthesia can cause bronchial spasm,lead to difficulty in ventilation and serious hypoxemia which may threaten the lives of patients.Propofol is a widely used intravenous anesthetic in clinic and its anti-inflammatory effect has received extensive attention.In studies of organ inflammatory lesions caused by infection or ischemia-reperfusion,it has been found that the anti-inflammatory effect of propofol is related to the regulation of TLR4/NF-κB signaling pathways and the decrease of intracellular ROS and oxidative stress.However,the effect of propofol on mast cell-dependent asthma remains unclear.Studies have shown that activation of toll-like receptor 4(TLR4)and its aptamer myeloid differentiation factor 88(MyD88),expressed on the surface of mast cells,can increase intracellular ROS and activate NF-κB which then stimulates mast cell synthesis and secretes of Th2 cytokines and eventually aggravates allergic asthma inflammation.Combined with the above evidence,we hypothesis that TLR4/MyD88/ROS/NF-KB signaling pathway participates in airway inflammation in mast cell-dependent asthmatic mice.Propofol can inhibit asthma inflammatory responses by regulating TLR4/MyD88/ROS/NF-KB signaling pathways.Therefore,this study established a mast cell-dependent asthma model,using propofol intervention,and measured the expression of TLR4/MyD88/ROS/NF-κB signaling pathway to investigate the impact of propofol on this type of asthma and anti-inflammatory effects.MethodsModel establishment and harvest:Female BALB/c mice,6 to 8 weeks old,weighing 20 to 25 g,randomly divided into four groups using random number table method.a.Normal control group(PBS):using PBS both sensitization and challenge;b.Asthma group(OVA):using OVA both sensitization and challenge;c.Propofol treatment group(OVA+PPF):intraperitoneal injection of propofol 100 mg/kg 30 min before OVA challenge;d.Intralipid treatment group(OVA+LIP):intraperitoneal injection of intralipid 100 mg/kg 30 min before OVA challenge.Mice were given intraperitoneal injections of 50 ug OVA for sensitization on days 1,3,5,and 7 and they were challenged with OVA intranasally on days 22,25,and 28.The mice were anesthetized on the 29th day and the lungs were lavaged with ice PBS to collect the alveolar lavage fluid(BALF).Right lung tissues were cryopreservated for protein detection.Left lung was fixed in 10%neutral formalin for pathological lung staining.ResultsCompared with the normal control group,the number of eosinophils,neutrophils and lymphocytes in the BALF of asthmatic mice was significantly increased.The levels of IL-4,IL-5,IL-6,IL-13,and TNF-a secretion in BALF of the asthma group were significantly increased.HE staining of the bronchioles in the asthma group showed that the the infiltration of peribronchial and perivascular inflammatory cells were significantly increased and the inflammation score was significantly increased.The bronchiolar goblet cell hyperplasia,mucus secretion and the PAS score were significantly increased in the asthma group.Compared with the asthma group,the cell and cytokines of the propofol-treated group was significantly reduced.The inflammation scores and the PAS score of the propofol-treated group were significantly lower than those in the asthma group.Compared with the normal control group,the expression of TLR4 and MyD88 in the lung of asthmatic mice was significantly increased;the levels of H2O2 and MDA in the asthma group were significantly increased,SOD levels were significantly reduced;the expression of I-κBα,p-I-κBα and p-NF-κBp65 was significantly decreased in the asthma group.Compared with the asthma group,the expression of TLR4 and MyD88 in the propofol-treated group was significantly reduced;the H2O2 and MDA were significantly decreased while SOD levels were significantly increased;the expression of I-κBαincreased,while the expression of p-I-κBα and p-NF-κBp65 were decreased.Conclusions1.Propofol reduces airway inflammation in mast cell-dependent asthmatic mice2.TLR4/MyD88/ROS/NF-KB signaling pathway involves airway inflammatory response in the mast cell-dependent asthmatic mice.3.Propofol inhibiting TLR4/MyD88/ROS/NF-KB signaling pathway may be one mechanism of reducing airway inflammation response in mice with mast cell-dependent asthma.Objective Although capnographic monitoring can decrease the rate of hypoxemia in patients undergoing some endoscopic procedures with sedation,extrapolation of using capnography in endoscopic sedition still contains controversy.We conducted a metaanalysis aim to determine whether added applying capnography in adults undergoing gastrointestinal endoscopy with sedation improves patient safety.Methods Ovid MEDLINE,EMB ASE,and the Cochrane Library databases were searched through from 26 September 2017.Randomized controlled trials(RCTs)on adults comparing additional capnography monitoring vs.standard monitoring for incidence of hypoxemia and severe hypoxemia in endoscopic sedation were included.Pooled relative risks(RRs)and 95% confidence intervals(CIs)were calcxxlated using random and fixed-effects models.Results Five studies comprising 2227 patients were identified.Compared with standard monitoring,added capnography significantly reduced hypoxemia(RR 0.76;95% Cl 0.63-0.91;P=0.003,I~2=64%)and severe hypoxemia(RR 0.63;95% Cl 0.44—0.90;P=0.01,I~2=55%).In a subgroup of procedure time ≥30 min? the decrease in hypoxemia(RR 0.65;95% Cl 0.56-0.75;P<0.001;P=3%)and severe hypoxemia(RR 0.62;95% Cl 0.47-0.83;P=0.001,I~2=12%)was observed.Capnography detected more apnea(RR 17.02;95% Cl6.90—41.99;P<0.001;I~2=69%)but had no benefit to other sedation related adverse events.Conclusions Intervention based on additional capnography could improve safety of adults undergoing gastrointestinal endoscopy with sedation by reducing the incidence of hypoxemia and severe hypoxemia,especially for the patients with long procedure time.