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Objective:To evaluate the effects of GSK484 on ventilator-induced lung injury (VILI) and neutrophil extracelluar traps (NETs) in mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 5-6 weeks, weighing 15-20 g, were divided into 4 groups ( n=12 each) by a random number table method: spontaneous breathing group (group S), spontaneous breathing+ GSK484 intervention group (group SG), VILI group (group V), and VILI + GSK484 intervention group (group VG). The animals kept spontaneous breathing for 4 h after tracheal intubation in S and SG groups. The animals were mechanically ventilated for 4 h (tidal volume 30 ml/kg, respiratory rate 75 breaths/min, inspiratory/expiratory ratio 1∶2, positive end-expiratory pressure 0 mmHg, fraction of inspired oxygen 21%) in V and VG groups. At 3 days before developing the VILI model, GSK484 4 mg/kg was intraperitoneally injected once a day in SG and VG groups, while the equal volume of normal saline was given instead in S and V groups. Blood samples were collected from the abdominal aorta for blood gas analysis at 4 h of spontaneous breathing or mechanical ventilation, and PaO 2 was recorded. The mice were then sacrificed and bronchoalveolar lavage fluid (BALF) was collected and lung tissues were obtained for microscopic examination of the pathological changes (with a light microscope after HE staining) which were scored and for determination of wet to dry weight ratio (W/D ratio), concentrations of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) in BALF (by enzyme-linked immunosorbent assay), expression of peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), high mobility group box 1 (HMGB1) and citrullinated-histone 3 (Cit-H3) in lung tissues (by Western blot). Results:Compared with S and SG groups, the lung injury score and W/D ratio were significantly increased, PaO 2 was decreased, concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were increased, and the expression of PAD4, NE, HMGB1 and Cit-H3 in lung tissues was up-regulated in V and VG groups ( P<0.05). Compared with group V, the lung injury score and W/D ratio were significantly decreased, PaO 2 was increased, the concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were decreased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was down-regulated in group VG ( P<0.05). Conclusions:GSK484 can alleviate VILI in mice, and the mechanism is associated with inhibition of PAD4, reduction of the production of NETs and attenuation of inflammatory responses in lung tissues.
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Objective:To evaluate the role of heat shock transcription factor 1 (HSF1) in the endogenous protective mechanism underlying mechanical ventilator-induced lung injury (VILI) in mice and the relationship with high mobility group box 1 (HMGB1).Methods:Forty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) by the random number table method: control group (group C), VILI group (group VILI), negative control siRNA + VILI group (group NV) and HSF1 siRNA + VILI group (group siRNA). At 48 h before mechanical ventilation, negative control siRNA 5 nmol and HSF1 siRNA 5 nmol were intratracheally injected in NV and siRNA groups respectively, and the solution was diluted to 50 μl with the sterile phosphate buffer in both groups. Group C kept spontaneous breathing for 4 h, and the rest animals were mechanically ventilated (tidal volume 35 ml/kg, respiratory rate 75 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%) for 4 h. Blood samples from the femoral artery were collected for arterial blood gas analysis immediately after endotracheal intubation and at 4 h of ventilation, and PaO 2 was recorded. Then the mice were sacrificed under deep anesthesia to collect lung tissues and bronchoalveolar lavage fluid (BALF). The concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and HMGB1 in BALF were determined by enzyme-linked immunosorbent assay. The pathological results were observed by hematoxylin-eosin staining, and lung injury was assessed and scored. The wet/dry (W/D) weight ratio of lung tissues was calculated. The expression of HMGB1 and HSF1 mRNA in lung tissues (by quantitative real-time polymerase chain reaction) and expression of HMGB1 and HSF1 protein in lung tissues (by Western blot) were determined. Results:Compared with group C, PaO 2 was significantly decreased at 4 h of ventilation, the concentrations of TNF-α, IL-1β and HMGB1 in BALF, W/D ratio and lung injury score were increased, and the expression of HMGB1 protein and mRNA in lung tissues was up-regulated in group VILI, group NV and group siRNA ( P<0.05 or 0.01). Compared with group VILI and group NV, PaO 2 was significantly decreased at 4 h of ventilation, the concentrations of TNF-α, IL-1β and HMGB1 in BALF, W/D ratio and lung injury score were increased, and the expression of HMGB1 protein and mRNA in lung tissues was up-regulated, and the expression of HSF1 protein and mRNA was down-regulated in group siRNA ( P<0.05 or 0.01). There was no significant difference in the parameters mentioned above between group VILI and group NV ( P>0.05). Conclusions:HSF1 is involved in the endogenous protective mechanism underlying VILI in mice, which may be related to the down-regulation of HMGB1 expression and attenuation of inflammatory responses in lung tissues.
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Objective:To evaluate the effect of irisin on the alveolar macrophage polarization in a rat model of ventilator-induced lung injury (VILI).Methods:Thirty SPF healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), VILI group (group V) and irisin group (group I). The rats were mechanically ventilation (tidal volume 20 ml/kg, respiratory rate 80 times/min, inhaled oxygen concentration 21%, inspiratory/expiratory ratio 1∶2, positive end-expiratory pressure 0) for 4 h to develop VILI model.Group C kept spontaneous breathing for 4 h. Irisin 1 μg/kg was injected via the tail vein at 30 min before tracheal intubation in group I, while the equal volume of normal saline was given instead in the other groups.The rats were sacrificed at 4 h of mechanical ventilation, the lung tissues were removed for examination of pathological changes which were scored and for determination of wet to dry weight ratio (W/D ratio), and bronchoalveolar lavage fluid (BALF) was collected for determination of concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and IL-10 (by enzyme-linked immunosorbent assay), expression of inducible nitric oxide synthase (iNOS), argininase 1 (Arg-1), and phosphorylated nuclear factor kappa B (p-NF-κB) p65 and p-NF-κB p50 in alveolar macrophages (by Western blot), and percentage of M1 and M2 alveolar macrophages and M1/M2 ratio (by flow cytometry). Results:Compared with group C, the W/D ratio, lung injury score, and concentrations of IL-6, TNF-α and IL-10 in BALF were significantly increased, the expression of iNOS, Arg-1, p-NF-κB p65 and p-NF-κB p50 was up-regulated, and the percentage of M1 and M2 alveolar macrophages and M1/M2 ratio were increased in group V and group I ( P<0.05). Compared with group V, the W/D ratio, lung injury score, and concentrations of IL-6 and TNF-α in BALF were significantly decreased, the expression of iNOS and p-NF-κB p65 was down-regulated, the percentage of M1 alveolar macrophages and M1/M2 ratio were decreased ( P<0.05), and no significant change was found in levels of IL-10 and Arg-1 in BALF, percentage of M2 alveolar macrophages and expression of p-NF-κB p50 in group I ( P>0.05). Conclusions:The mechanism by which irisin reduces VILI may be related to inhibition of NF-κB signaling pathway activation and reduction of alveolar macrophage polarization to M1 phenotype in rats.
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Objective:To evaluate the role of cathepsin B (CTSB) in mechanical ventilator-induced lung injury (VILI) in rats and the relationship with NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome.Methods:Thirty-six SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 220-300 g, were divided into 3 groups ( n=12 each) by the random number table method: control group (group C), VILI group (group V) and VILI + CA074-me group (group Me). CA074-me 5 mg/kg was intraperitoneally injected in group Me, while the equal volume of normal saline was given instead in group C and group V. Group C kept spontaneous breathing for 4 h, and the animals were mechanically ventilated (tidal volume 20 ml/kg, respiratory rate 80 breaths/min, fraction of inspired oxygen 21%, PEEP 0 cmH 2O). Blood samples from femoral artery were collected for arterial blood gas analysis before tracheal intubation and after spontaneous breathing or ventilation, and PaO 2 was recorded.Rats were sacrificed, and bronchoalveolar lavage fluid (BALF) was collected and lung tissues were collected for determination of the wet/dry lung weight ratio (W/D ratio), serum interleukin-1beta (IL-1β) and IL-18 concentrations in BALF (by enzyme-linked immunosorbent assay), expression of CTSB, NLRP3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) and caspase-1 mRNA in lung tissues (quantitative real-time polymerase chain reaction), and expression of CTSB, NLRP3, ASC and caspase-1 in lung tissues (by Western blot) and for microscopic examination of the pathological changes (using HE staining). Lung injury was assessed and scored. Results:Compared with group C, PaO 2 was significantly decreased after the end of ventilation, the lung injury score, W/D ratio and concentrations of IL-1β and IL-18 in serum and BALF were increased, and the expression of CTSB, NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was up-regulated in group V and group Me ( P<0.01). Compared with group V, PaO 2 was significantly increased after the end of ventilation, the lung injury score, W/D ratio and concentrations of IL-1β and IL-18 in serum and BALF were decreased, and the expression of CTSB, NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was down-regulated in group Me ( P<0.01). Conclusions:CTSB is involved in VILI in the rats, and the mechanism may be related to activation of NLRP3 inflammasomes.
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Objective:To compare the efficacy of different concentrations of ropivacaine for interscalene brachial plexus block in patients undergoing arthroscopic shoulder surgery under general anesthesia.Methods:Ninety American Society of Anesthesiologists physical statusⅠor Ⅱ patients (NYHA classⅠorⅡ) of both sexes, aged 18-64 yr, with body mass index of 18.0-26.9 kg/m 2, undergoing elective arthroscopic shoulder surgery were selected, and were divided into 3 groups ( n=30 each) using a random number table method: 0.25% ropivacaine group (group A), 0.375% ropivacaine group (group B) and 0.5% ropivacaine group (group C). Interscalene brachial plexus block was performed with 0.25%, 0.375% and 0.5% ropivacaine 20 ml in A, B and C groups, respectively.Before operation (T 0) and at 30 min (T 1), 4 h (T 2), 6 h (T 3), 8 h (T 4), 10 h (T 5) and 12 h (T 6) after administration, the diaphragmatic mobility was measured and recorded using M-mode ultrasound and forced expiratory volume in the first second (FEV 1) and forced vital capacity (FVC) were measured using portable spirometer.The occurrence of phrenic paralysis was recorded at T 1-6.The duration of sensory and motor block was recorded.When visual analogue scale score>3 within 24 h after operation, flurbiprofen axetil 50 mg was injected intravenously for analgesia and the consumption was recorded.The adverse reactions such as cardiovascular events, local anesthetic intoxication, Horner syndrome, pneumothorax, and nausea and vomiting within 24 h after administration were recorded. Results:Compared with group A, the diaphragmatic mobility was significantly decreased during quiet breathing at T 1-3 and was decreased during deep breathing at T 2-5, and the diaphragmatic paralysis rate was increased during quiet and deep breathing at T 2-3 in group B, diaphragmatic mobility was decreased during quiet and deep breathing at T 1-6, diaphragmatic paralysis rate was increased during quiet and deep breathing at T 1-4, FEV 1% and FVC% were decreased at T 1 and FVC% was decreased at T 2 in group C, and the duration of sensory and motor block was prolonged in B and C groups ( P<0.05 or 0.01). Compared with group B, the diaphragmatic mobility was significantly decreased during quiet breathing at T 4-6 and was decreased during deep breathing at T 1-6, the diaphragmatic paralysis rate during quiet breathing was increased at T 2-4 ( P<0.05) was increased during deep breathing at T 3-4, and FEV 1 % and FVC % at T 1 were decreased in group C ( P<0.05). There was no significant difference in the postoperative requirement for flurbiprofen axetil and the incidence of adverse reactions within 24 h after administration among the 3 groups ( P>0.05). Conclusion:0.25% ropivacaine 20ml provides better efficacy when used for interscalene brachial plexus block in the patients undergoing arthroscopic shoulder surgery.
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Objective:To investigate the effect of irisin on pyroptosis in rats with ventilator-induced lung injury.Methods:Thirty-six healthy clean-grade male Sprague-Dawley rats, weighing 200-250 g, aged 6-8 weeks, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), ventilator-induced lung injury group (group V) and ventilator-induced lung injury plus irisin group (group V+ I). In group V+ I, irisin 1 μg/kg was injected via the tail vein before mechanical ventilation.The animals were mechanically ventilated (tidal volume of 40 ml/kg, respiratory rate 60 breaths/min, inspiratory/expiratory ratio 1∶2, positive end expiratory pressure 0 and inspired oxygen fraction ratio 21%.Blood samples were then taken from the femoral artery for blood gas analysis, and PaO 2 was recorded.Bronchoalveolar lavage fluid (BALF) was collected, the total protein concentrations in BALF were measured, and the concentrations of BALF and serum interleukin-1β (IL-1β) and IL-18 were measure by enzyme-linked immunosorbent assay.The lung tissues were obtained for determination of the pathological changes after HE staining which were scored, wet to dry weight (W/D) ratio, expression of pyroptosis-related proteins N-terminal gasdermin D (GSDMD-N) and caspase-1 protein and mRNA (by Western blot or using real-time polymerase chain reaction). Results:Compared with group C, the lung injury score and W/D ratio were significantly increased, PaO 2 and OI were decreased, the total protein concentrations in BALF, concentrations of IL-1β and IL-18 in BALF and serum were increased, and the expression of caspase-1 and GSDMD-N protein and mRNA was up-regulated in group V ( P<0.01). Compared with group V, the lung injury score and W/D ratio were significantly decreased, PaO 2 and OI were increased, the total protein concentrations in BALF, concentrations of serum IL-1β and IL-18 in BALF and serum were decreased, and the expression of caspase-1 and GSDMD-N protein and mRNA was down-regulated in group V+ I ( P<0.01). Conclusion:The mechanism by which irisin reduces ventilator-induced lung injury is probably related to inhibiting pyroptosis in rats.
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Objective:To evaluate the effect of irisin on ventilator-induced lung injury (VILI) in rats and the relationship with expression of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes.Methods:Thirty-six SPF-grade healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 220-300 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), group VILI and irisin group (group I). All the groups underwent tracheotomy and intubation, group C kept spontaneous breathing for 4 h, and the animals were mechanically ventilated for 4 h in VILI and I groups.Irisin 1 μg/kg was injected via the tail vein at 30 min before tracheal intubation in group I, and the equal volume of normal saline mixture (normal saline∶phosphate buffer solution containing 5% trehalose=1∶9) were given in the other 2 groups via the tail vein.The rats were mechanically ventilated with the tidal volume of 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, inspired oxygen fraction ratio 21% and positive end-expiratory pressure 0.Blood samples from left femoral artery were collected before tracheal intubation and at the end of mechanical ventilation for detection of PaO 2.The animals were sacrificed and the lung tissue samples and bronchoalveolar lavage fluid (BALF) were then collected for examination of the pathological changes (under the light microscope), and for determination of wet to dry weight (W/D) ratio and the concentrations of total protein in BALF and interleukin-1β (IL-1β) and IL-18 in BALF and serum (by enzyme-linked immunosorbent assay), level of reactive oxygen species (ROS) in alveolar macrophages in BALF (by DCFH-DA) and the expression of NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 protein and mRNA in lung tissues (by Western blot and by quantitative reverse transcription polymerase chain reaction). The pathological changes of the lung were scored. Results:Compared with group C, PaO 2 was significantly decreased at the end of mechanical ventilation, lung injury score and W/D ratio were increased, concentration of total protein and ROS level in alveolar macrophages in BALF and concentrations of BALF, IL-1β and IL-18 in serum were increased, and the expression of NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was up-regulated in group VILI and group I ( P<0.01). Compared with group VILI, PaO 2 was significantly increased at the end of mechanical ventilation, lung injury score and W/D ratio were decreased, concentration of total protein and ROS level in alveolar macrophages in BALF and concentrations of BALF, IL-1β and IL-18 in serum were decreased, and the expression of NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was down-regulated in group I ( P<0.05). Conclusion:Irisin can reduce VILI, and the mechanism is related to inhibiting activation of NLRP3 inflammasome and reducing inflammatory response in rats.
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Objective:To evaluate the effect of rapamycin on the activity of NOD-like receptor C4 (NLRC4) inflammasomes in the rats with ventilator-induced lung injury (VILI).Methods:Thirty-six healthy clean-grade male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), VILI group and rapamycin group (group RAPA). In group RAPA, rapamycin 4 mg·kg -1·d -1 was intraperitoneally injected once a day for 3 consecutive days before establishing the model, while the equal volume of normal saline was given instead in group C and group VILI.The patients were mechanically ventilated for 4 h (tidal volume 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, fraction of inspired oxygen 21%) in VILI and RAPA groups.Blood samples were collected from the femoral artery after the end of ventilation for blood gas analysis and for determination of serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) concentrations (by enzyme-linked immunosorbent assay), and PaO 2 was recorded.The bronchoalveolar lavage fluid (BALF) was collected for determination of the neutrophil count and IL-1β and IL-18 concentrations by enzyme-linked immunosorbent assay.The lung tissues were obtained for examination of the pathological changes (under the light microscope) after HE staining which were scored and for determination of wet to dry weight (W/D) ratio, and expression of mammalian target of rapamycin (mTOR), NLRC4 and caspase-1 (by Western blot) and expression of NLRC4 mRNA (by real-time polymerase chain reaction). Results:Compared with group C, the W/D ratio, lung injury score, neutrophil counts in BALF, and concentrations of IL-1β and IL-18 in serum and BALF were significantly increased, PaO 2 was decreased, and the expression of mTOR, NLRC4, caspase-1 and NLRC4 mRNA was up-regulated in group VILI and group RAPA ( P<0.01). Compared with group VILI, the W/D ratio, lung injury score, neutrophil counts in BALF, and concentrations of IL-1β and IL-18 in serum and BALF were significantly decreased, PaO 2 was increased, and the expression of mTOR, NLRC4, caspase-1 and NLRC4 mRNA was down-regulated in group RAPA ( P<0.05). Conclusion:The mechanism by which rapamycin alleviates VILI may be related to inhibiting activation of mTOR signaling pathway and inhibiting the activity of NLRC4 inflammasomes in rats.
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Objective:To evaluate the obesity factor on ventilator-induced lung injury (VILI) in rats.Methods:Forty-five clean-grade male Sprague-Dawley rats, aged 6-8 weeks, were divided into 3 groups ( n = 15 each)according to the body weight: normal weight control group (group C), normal weight VILI group (group CV) and obese VILI group (group FV). The body weight was 233-267 g in C and CV groups and 288-332 g in FV group.In group C, the tidal volume (V T) was 10 ml/kg.In CV and FV groups, the rats were ventilated for 4 h with the V T set at 40 ml/kg, respiratory rate 40 breaths/min, inspiratory/expiratory ratio 1∶2, PEEP 0 mmHg, and fraction of inspired oxygen 21% to establish the VILI model.The arterial blood samples were collected immediately before tracheal intubation and at 4 h of mechanical ventilation for blood gas analysis and PaO 2 recording.The remaining blood samples were used for plasma collection.The rats were sacrificed after blood collection at 4 h of ventilation, and the bilateral lung tissues were isolated to collect the bronchoalveolar lavage fluid (BALF). The concentrations of leptin in plasma and tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) in plasma and BALF were detected by enzyme-linked immunosorbent assay.The wet/dry weight (W/D) ratio of lung tissues was measured.The pathological changes of lung tissues were observed after HE staining, and the lung injury score was evaluated.The expression of NF-κB p65 in lung tissues was detected by Western blot. Results:Compared with group C and group CV, the plasma leptin concentration was significantly increased in group FV( P<0.01). Compared with group C, the concentrations of TNF-α, IL-6 and IL-1β in plasma and BALF were significantly increased, PaO 2 was decreased, the lung injury score and W/D ratio of lung tissues were increased, and NF-κB p65 expression was up-regulated at 4 h of ventilation in CV and FV groups ( P<0.01). Compared with group CV, the concentrations of TNF-α, IL-6 and IL-1β in plasma and BALF were significantly decreased, PaO 2 was increased, the lung injury score and W/D ratio of lung tissues were decreased, and NF-κB p65 expression was down-regulated at 4 h of ventilation in group FV ( P<0.05). Conclusion:Obesity factor can reduce VILI in rats, and the mechanism may be related to the increase in plasma leptin levels.
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Objective:To evaluate the role of protein kinase C-delta (PKC-δ) in ventilator-induced lung injury (VILI) and the relationship with NLR family CARD domain-containing protein 4 (NLRC4) in rats.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), VILI group (group V) and VILI plus KAI 9803 group (group VK). In V and VK groups, tracheal tubes were placed for mechanical ventilation after tracheotomy, ventilator settings were adjusted with a tidal volume of 40 ml/kg, respiratory rate of 60 breaths/min, and inspiratory/expiratory ratio of 1∶2, and air was inhaled.Group C received no mechanical ventilation after tracheal intubation.Immediately after completion of intubation, PKC-δ specific inhibitor KAI 9803 200 μg/kg was intratracheally injected in group VK, and the equal volume of phosphate buffer saline was given instead in the other two groups.Blood samples were taken from the femoral artery at 4 h of mechanical ventilation to record PaO 2.The chest was opened at the end of mechanical ventilation, lung tissues were removed, and the left lung tissues were lavaged to collect bronchoalveolar lavage fluid (BALF). The pathological changes of lung tissues were examined with a light microscope and scored.Enzyme-linked immunosorbent assay was used to detect the concentrations of interleukin-1beta (IL-1β) and IL-18 in BALF, Western blot was used to detect the expression of NLRC4, caspase-1 and PKC-δ in the right lower lobe of the lung, and the expression of NLRC4 mRNA in the right lower lobe of the lung was determined by real-time polymerase chain reaction, and the wet/dry weight ratio (W/D ratio) of the right middle lobe of the lung was calculated. Results:Compared with group C, the pathological score and W/D ratio were significantly increased, PaO 2 was decreased, the concentrations of IL-1β and IL-18 in BALF were increased, and the expression of NLRC4, caspase-1 and NLRC4 mRNA was up-regulated in V and VK groups, and the expression of PKC-δ was significantly up-regulated ( P<0.01), and a large amount of edema fluid was seen in the alveolar space, with inflammatory cell infiltration in group V ( P<0.01). Compared with group V, the pathological score and W/D ratio were significantly decreased, PaO 2 was increased, the concentrations of IL-1β and IL-18 in BALF were decreased, the expression of NLRC4, caspase-1, PKC-δ and NLRC4 mRNA was down-regulated ( P<0.05), and fluid exudation in the alveolar space and the degree of inflammatory cell infiltration were significantly attenuated in group VK. Conclusion:PKC-δ is involved in VILI, which is related to inhibiting NLRC4 expression in rats.
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Objective@#To evaluate the effect of penehyclidine hydrochloride on the expression of airway mucin 5AC (MUC5AC) during ventilator-induced lung injury (VILI) and the relationship with Toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway in rats.@*Methods@#Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 3 groups (n=12 each) using a random number table method: sham operation group (group S), VILI group (group VILI), and penehyclidine hydrochloride group (group P). The rats were tracheotomized in group S. The rats were tracheotomized, connected to a small animal ventilator and mechanically ventilated for 4 h with the tidal volume of 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, and inspired oxygen fraction ratio 21% in VILI and P groups.At 30 min before mechanical ventilation, penehyclidine hydrochloride 2 mg/kg was injected via the tail vein in group P, and the equal volume of normal saline was given instead in S and VILI groups.At 4 h of mechanical ventilation, the arterial blood samples were taken for measurement of PaO2.The rats were then sacrificed, and broncho-alveolar lavage fluid (BALF) was collected for determination of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) concentrations by enzyme-linked immunosorbent assay.The lung specimens were collected for calculation of the wet/dry weight ratio (W/D ratio), for examination of pathological changes which were scored after haematoxylin and eosin staining (under a light microscope), and for determination of the expression of MUC5AC (by immunohistochemistry), expression of TLR4, MyD88, p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kappa B (NF-κB) in lung tissues (by Western blot), and expression of MUC5AC mRNA in lung tissues (by real-time polymerase chain reaction).@*Results@#Compared with group S, PaO2 was significantly decreased, the W/D ratio and lung injury score were increased, the expression of MUC5AC protein and mRNA was up-regulated, the concentrations of IL-1β, IL-6 and TNF-α in BALF were increased, and the expression of TLR4, p38MAPK, MyD88 and NF-κB was up-regulated in VILI and P groups (P<0.01). Compared with group VILI, PaO2 was significantly increased, the W/D ratio and lung injury score were decreased, the expression of MUC5AC protein and mRNA was down-regulated, the concentrations of IL-1β, IL-6 and TNF-α in BALF were decreased, and the expression of TLR4, p38MAPK, MyD88 and NF-κB was down-regulated in group P (P<0.05).@*Conclusion@#Penehyclidine hydrochloride can decrease the expression of airway MUC5AC during VILI, and the mechanism may be related to inhibiting activation of TLR4/MyD88 signaling pathway in rats.
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Objective@#To compare the effect of total intravenous anesthesia with propofol and combined intravenous-inhalational anesthesia with sevoflurane on postoperative sleep quality in elderly female patients.@*Methods@#One hundred and twenty patients, aged 65-80 yr, with body mass index of 18.5-25.0 kg/m2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for elective gynecological laparoscopic operation, were divided into 2 groups (n=60 each) by a random number table method: total intravenous anesthesia with propofol group (group P) and combined intravenous-inhalational anesthesia with sevoflurane group (group S). Anesthesia was induced with intravenous etomidate 0.2-0.3mg/kg, sufentanil 0.2-0.4 μg/kg and cisatracurium 0.10-0.15 mg/kg.Anesthesia was maintained as follows: propofol was given by target-controlled infusion with the target plasma concentration set at 2-4 μg/ml in group P, 1.2-2.3% sevoflurane was inhaled in group S, and sufentanil 0.2-0.3 μg/kg and cisatracurium 0.04-0.06 mg/kg were intermittently injected in two groups.The patients were followed up at 7-8 a. m.on the day of hospitalization, the day of operation and 1, 3, 7 and 30 days after operation.The Pittsburgh Sleep Quality Index (PSQI) was recorded, PSQI > 7 points was considered as sleep disorders, and the occurrence of sleep disorders was recorded.The morning urine was collected at the time points mentioned above, and the concentrations of melatonin sulfate and free cortisol were determined by enzyme-linked immunosorbent assay.@*Results@#Compared with group S, the PSQI was significantly decreased on 3 and 7 days after operation, the incidence of sleep disorder was decreased on 7 days after operation, the concentrations of melatonin sulfate in urine were increased (P<0.05), and no significant change was found in free cortisol in urine in group P (P>0.05).@*Conclusion@#The effect of total intravenous anesthesia with propofol on postoperative sleep quality is less than that of combined intravenous-inhalational anesthesia with sevoflurane in elderly female patients.
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Objective To evaluate the effect of penehyclidine hydrochloride on the expression of airway mucin 5AC(MUC5AC)during ventilator-induced lung injury(VILI)and the relationship with Toll-like receptor 4/myeloid differentiation factor 88(TLR4/MyD88)signaling pathway in rats.Methods Thir-ty-six clean-grade healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-250 g,were divided into 3 groups(n＝12 each)using a random number table method: sham operation group(group S),VILI group(group VILI),and penehyclidine hydrochloride group(group P).The rats were tracheotomized in group S.The rats were tracheotomized,connected to a small animal ventilator and mechanically ventilated for 4 h with the tidal volume of 20 ml/kg,respiratory rate 80 breaths/min,inspiratory/expiratory ratio 1 ∶1,and inspired oxygen fraction ratio 21％in VILI and P groups.At 30 min before mechanical ventilation,penehyclidine hydrochloride 2 mg/kg was injected via the tail vein in group P,and the equal volume of nor-mal saline was given instead in S and VILI groups.At 4 h of mechanical ventilation,the arterial blood sam-ples were taken for measurement of PaO2.The rats were then sacrificed,and broncho-alveolar lavage fluid(BALF)was collected for determination of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)concentrations by enzyme-linked immunosorbent assay.The lung specimens were collected for calculation of the wet/dry weight ratio(W/D ratio),for examination of pathological changes which were scored after haematoxylin and eosin staining(under a light microscope),and for determination of the ex-pression of MUC5AC(by immunohistochemistry),expression of TLR4,MyD88,p38 mitogen-activated protein kinase(p38MAPK)and nuclear factor-kappa B(NF-κB)in lung tissues(by Western blot),and expression of MUC5AC mRNA in lung tissues(by real-time polymerase chain reaction).Results Com-pared with group S,PaO2 was significantly decreased,the W/D ratio and lung injury score were increased,the expression of MUC5AC protein and mRNA was up-regulated,the concentrations of IL-1β,IL-6 and TNF-α in BALF were increased,and the expression of TLR4,p38MAPK,MyD88 and NF-κB was up-reg-ulated in VILI and P groups(P＜0.01).Compared with group VILI,PaO2 was significantly increased,the W/D ratio and lung injury score were decreased,the expression of MUC5AC protein and mRNA was down-regulated,the concentrations of IL-1β,IL-6 and TNF-α in BALF were decreased,and the expression of TLR4,p38MAPK,MyD88 and NF-κB was down-regulated in group P(P＜0.05).Conclusion Penehy-clidine hydrochloride can decrease the expression of airway MUC5AC during VILI,and the mechanism may be related to inhibiting activation of TLR4/MyD88 signaling pathway in rats.
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Objective To compare the effect of total intravenous anesthesia with propofol and com-bined intravenous-inhalational anesthesia with sevoflurane on postoperative sleep quality in elderly female patients.Methods One hundred and twenty patients,aged 65-80 yr,with body mass index of 18.5-25.0 kg/m2,of American Society of Anesthesiologists physical status Ⅰ-Ⅲ,scheduled for elective gyne-cological laparoscopic operation,were divided into 2 groups(n＝60 each)by a random number table meth-od: total intravenous anesthesia with propofol group(group P)and combined intravenous-inhalational anes-thesia with sevoflurane group(group S).Anesthesia was induced with intravenous etomidate 0.2-0.3 mg/kg,sufentanil 0.2-0.4 μg/kg and cisatracurium 0.10-0.15 mg/kg.Anesthesia was maintained as fol-lows: propofol was given by target-controlled infusion with the target plasma concentration set at 2-4 μg/ml in group P,1.2-2.3％sevoflurane was inhaled in group S,and sufentanil 0.2-0.3 μg/kg and cisatracuri-um 0.04-0.06 mg/kg were intermittently injected in two groups.The patients were followed up at 7-8 a.m.on the day of hospitalization,the day of operation and 1,3,7 and 30 days after operation.The Pittsburgh Sleep Quality Index(PSQI)was recorded,PSQI> 7 points was considered as sleep disorders,and the oc-currence of sleep disorders was recorded.The morning urine was collected at the time points mentioned a-bove,and the concentrations of melatonin sulfate and free cortisol were determined by enzyme-linked immu-nosorbent assay.Results Compared with group S,the PSQI was significantly decreased on 3 and 7 days after operation,the incidence of sleep disorder was decreased on 7 days after operation,the concentrations of melatonin sulfate in urine were increased(P＜0.05),and no significant change was found in free cortisol in urine in group P(P>0.05).Conclusion The effect of total intravenous anesthesia with propofol on postoperative sleep quality is less than that of combined intravenous-inhalational anesthesia with sevoflurane in elderly female patients.
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Objective To evaluate the effect of electroacupuncture (EA) preconditioning on inositol-requiring kinase 1 (IRE1)-X-box binding protein 1 (XBP1) signaling pathway in endoplasmic reticulum in the cortex in a rat model of cerebral ischemia-reperfusion (I/R).Methods One hundred and eight pathogen-free healthy male Sprague-Dawley rats,aged 8-12 weeks,weighing 200-250 g,were assigned into 3 groups (n =36 each) using a random number table:sham operation group (group S),group I/R and EA preconditioning group (group EA).Focal cerebral I/R was induced by occlusion of right middle cerebral arteries for 2 h followed by reperfusion in rats anesthetized with chloral hydrate.In group EA,Baihui acupoints were stimulated with an electric stimulator for 30 min once a day for 5 consecutive days starting from 5 days before ischemia,and the model was established at 24 h after the last preconditioning.Rats were sacrificed after neurological deficit was scored at 6,12 and 24 h of reperfusion,brains were removed,and the ischemic area in cerebral cortex was isolated for examination of the cell ultrastructure (with an electronic microscope) and for determination of the expression of IRE1 and XBP1 (by Western blot).Results Compared with group S,the neurological deficit scores were significantly increased,and the expression of IRE1 and XBP1 in the ischemic area was up-regulated at each time point in I/R and EA groups (P＜0.01).Compared with group I/R,the neurological deficit scores were significantly decreased,and the expression of IRE1 and XBP1 was up-regulated at each time point in group EA (P＜0.05).The cell damage in the ischemic area in cerebral cortex was significantly attenuated in group EA when compared with group I/R.Conclusion The mechanism by which EA preconditioning attenuates cerebral I/R injury is related to activating IRE1-XBP 1 signaling pathway and relieving endoplasmic reticulum stress in rats.
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Objective To investigate the effect of acupuncture on cholinergic anti-inflammatory pathway in the hippocampus of aged rats during global cerebral ischemia-reperfusion ( I∕R ) . Methods Ninety-six clean-grade healthy male Sprague-Dawley rats, aged 17-22 months, weighing 440-580 g, were divided into 3 groups ( n=32 each) using a random number table method: sham operation group ( group S), global cerebral I∕R group (group I∕R) and acupuncture group (group AP). Global cerebral I∕R was induced by 4-vessel occlusion method described by Pulsinelli in group I∕R and group AP. Baihui and Feng-chi were stimulated for 14 consecutive days before ischemia in group AP. Four rats were sacrificed at 1, 3, 5 and 7 days of reperfusion, and brains were removed for determination of neuronal apoptosis by TUNEL. Four rats were sacrificed at 1, 3, 5 and 7 days of reperfusion, and brains were removed for determination of the expression of α7 nicotinic acetylcholine receptor (α7nAChR), choline acetyltransferase (ChAT), tumor necrosis factor-α ( TNF-α) and interleukin-1β ( IL-1β) in the hippocampal CA1 region by Western blot. The apoptosis rate was calculated. Results Compared with group S, the apoptosis rate of hippocam-pal neurons was significantly increased, and the expression of α7nAChR, ChAT, TNF-α and IL-1β was up-regulated at each time point of reperfusion in I∕R and AP groups ( P<0. 05) . Compared with group I∕R, the apoptosis rate of hippocampal neurons was significantly decreased, the expression of α7nAChR and ChAT was up-regulated, and the expression of TNF-α and IL-1β was down-regulated at each time point ofreperfusion in group AP (P<0. 05). Conclusion The mechanism by which acupuncture mitigates global cerebral I∕R injury may be related to activating cholinergic anti-inflammatory pathway in the hippocampus of aged rats.
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Objective To evaluate the efficacy of oxycodone combined with thoracic paravertebral block ( TPVB) for postoperative analgesia in patients undergoing minimally invasive direct coronary artery bypass grafting ( MIDCABG) . Methods Thirty-two American Society of Anesthesiologists physical statusⅡorⅢpatients of both sexes, aged 60-75 yr, weighing 50-85 kg, scheduled for elective MIDCABG un-der general anesthesia, were divided into 2 groups ( n=16 each) using a random number table method:morphine plus TPVB group ( group MT) and oxycodone plus TPVB group ( group OT) . Paravertebral cathe-ter was placed at T4,5 before induction of anesthesia to perform left thoracic paravertebral puncture, patients were tracheally intubated, and 0. 375％ ropivacaine 15 ml was injected followed by continuous infusion of 0. 375％ ropivacaine 5 ml∕h until 0. 5 h before the end of surgery. Both groups received patient-controlled analgesia ( PCA) after surgery. The PCA solution contained 1 mg∕ml morphine 60 ml in group MT or 1 mg∕ml oxycodone 60 ml in group OT, and the PCA pump was set up to deliver a 1 mg bolus dose with a 10-min lockout interval and background infusion at 1 ml∕h after a loading dose of 2 mg, with the maximum dose of 20 mg every 4 h. Pethidine 50 mg was intravenously injected as a rescue analgesic to maintain visual ana-log scale≤4. The intraoperative consumption of fentanyl, consumption of analgesics for PCA within 48 h after surgery, ratio of total to effective pressing times of PCA, consumption of analgesics for rescue analge-sia, requirement for rescue analgesia, score of satisfactory analgesia, extubation time, duration of inten-sive care unit stay and length of hospital stay were recorded. The development of nausea and vomiting, pru-ritus, respiratory depression, atelectasis and somnolence was recorded within 72 h after surgery. Results Compared with group MT, the intraoperative consumption of fentanyl, consumption of analgesics for PCA, consumption of analgesics for rescue analgesia, requirement for rescue analgesia and ratio of total to effec-tive pressing times of PCA were significantly decreased, the score of satisfactory analgesia was increased, the extubation time and duration of intensive care unit stay were shortened, and the incidence of nausea and vomiting, pruritus, respiratory depression and somnolence was decreased in group OT (P<0. 05). Con-clusion Oxycodone combined with TPVB provides safe and effective efficacy for postoperative analgesia in patients undergoing MIDCABG.
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Objective To evaluate the effect of PUN282987 on global cerebral ischemia-reperfusion (I/R) injury in aged rats.Methods One hundred and twenty pathogen-free healthy male SpragueDawley rats,aged 18-22 months,weighing 450-600 g,were divided into 3 groups (n=40 each) using a random number table:sham operation group (group S),global cerebral I/R group (group I/R) and α7 nicotinic acetylcholine receptor (α7nAChR) agonist PNU282987 group (group PUN).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 0.4 ml/100g,and global cerebral I/R was produced by 4-vessel occlusion technique in I/R and PUN groups.PUN282987 2.4 mg/kg was injected intraperitoneally before ischemia in group PUN.At 1,5,12 and 24 h of reperfusion,10 rats were randomly selected in each group and then sacrificed,and the brains were removed for detection of the neuronal apoptosis and for determination of the expression of α7nAChR,choline acetyltransferase (ChAT),tumor necrosis factor-α (TNF-α) and intedeukin-1β (IL-1β) in the hippocampal CA1 region.Apoptosis rate was calculated.Results Compared with group S,the apoptosis rate was significantly increased,and the expression of α7nAChR,ChAT,TNF-α and IL-1β was up-regulated at each time point in I/R and PUN groups (P＜0.05).Compared with group I/R,the apoptosis rate was significantly decreased,the expression of α7nAChR and ChAT was up-regulated,and the expression of TNF-α and IL-1β was down-regulated at each time point in group PUN (P＜0.05).Conclusion PUN282987 can reduce global cerebral I/R injury in aged rats.
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Objective To evaluate the effect of mild hypothermia on the activity of hippocampal pro tein kinase R-like endoplasmic reticulum kinase (PERK) in a mouse model of cerebral ischemia-reperfusion (I/R).Methods One hundred and twenty male C56BL6 mice,weighing 20-30 g,aged 7 weeks,were randomly divided into 3 groups (n=40 each) using a random number table:sham operation group (group S),I/R group,and mild hypothermia group (group H).Cerebral I/R was induced by occlusion of bilateral common carotid arteries for 15 min followed by reperfusion in anesthetized mice.In group H,surface cooling was performed immediately after reperfusion,and the rectal temperature was maintained at 32-34 ℃ for 3 h.In I/R and S groups,the rectal temperature was maintained at 36.8-37.2 ℃.At 6,12,24 and 72 h of reperfusion,10 mice were sacrificed in each group,and the hippocampi were removed for determination of the number of apoptotic neurons in hippocampal CA1 region (by TUNEL),and phosphorylated PERK (p-PERK) expression (by Western blot).Results Compared with group S,the number of apoptotic neurons was significantly increased,and the expression of p-PERK was up-regulated at each time point in I/R and H groups (P＜0.05).Compared with group I/R,the number of apoptotic neurons was significantly decreased,and the expression of p-PERK was downregulated at each time point in group H (P＜0.05).Conclusion Mild hypothermia can reduce endoplasmic reticulum stress through inhibiting hippocampal PERK activity,thus attenuating cerebral injury in a mouse model of cerebral I/R.
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Objective To evaluate the efficacy of thoracic paravertebral block for preemptive analgesia in the patients undergoing minimally invasive direct coronary artery bypass grafting (MIDCAB).Methods Sixty patients of both sexes,aged 54-75 yr,weighing 55-82 kg,of American Society of Anesthesiologists physical Ⅱ or Ⅲ,with New York Heart Association Ⅰ-Ⅲ,scheduled for elective MIDCAB,were randomly divided into 2 groups (n =30 each) by using a random number table:control group (group C) and thoracic paravertebral block group (group P).Thoracic paravertebral block was performed under the guidance of a nerve stimulator in group P.A paravertebral catheter was placed at T4,5 interspace,a test dose of 0.5％ ropivacacine 5 ml was injected through the catheter,and 5 min later a bolus dose of 0.5％ ropivacacine 15 ml was injected.Anesthesia was induced with intravenous etomidate,midazolam,fentanyl and vecuronium.All the patients were intubated with a double-lumen endobronchial tube and mechanically ventilated,and end-tidal pressure of carbon dioxide was maintained at 30-40 mmHg.Anesthesia was maintained with intravenous injection of fentanyl and vecuronium,intravenous infusion of propofol,and inhalation of sevoflurane.Bispectral index value was maintained at 40-60.When systolic blood pressure ＞ 160 mmHg,fentanyl 0.1 mg was injected intravenously.Both groups started to receive patient-controlled intravenous analgesia (PCIA) after extubation until 48 h after operation.PCIA solution contained morphine in 100 ml of normal saline.The PCIA pump was set up with a 2 mg bolus dose,a 10 min lockout interval and background infusion at a rate of 0.5 mg/h.Visual analogue scale was maintained ≤ 4.When visual analogue scale＞4,morphine 4 mg was injected intravenously as rescue analgesic.The consumption of intraoperative fentanyl was recorded.The consumption of morphine and requirement for rescue analgesics were recorded within 24 and 48 h after operation.The adverse reactions such as somnolence,nausea and vomiting,respiratory depression,pruritus,and atelectasis were recorded within 48 h after operation.The extubation time after operation,length of time in intensive care unit,and recovery time after operation were recorded.At 24 and 48 h after operation,pulmonary function was detected,the forced vital capacity (FVC) expressed as a percentage of the predicted value (FVC％),and forced expiratory volume in 1 second (FEV1)expressed as a percentage of the predicted value (FEV1 ％) were recorded,and the ratio of FEV1/FVC was calculated.Blood gas analysis was performed,and arterial oxygen partial pressure and partial pressure of arterial carbon dioxide were recorded at 24 and 48 h after operation.Results Compared with group C,the intraoperative consumption of fentanyl and consumption of morphine within 24 and 48 h after operation were significantly reduced,the extubation time and length of time in intensive care unit were shortened,FVC％ and FEV1％ were increased at 24 and 48 h after operation,the partial pressure of arterial carbon dioxide and incidence of somnolence were decreased (P＜0.05),and no significant change was found in the FEV1 / FVC,arterial oxygen partial pressure,requirement for rescue analgesics and recovery time after operation in group P (P＞0.05).Conclusion Thoracic paravertebral block analgesia can provide good preempive analgesia in the patients undergoing MIDCAB.