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Objective:To observe the effect of ventilator-induced lung injury (VILI) on blood-brain barrier permeability in rats.Methods:Forty-eight healthy clean male Sprague-Dawley (SD) rats were randomly divided into sham operation (Sham) group, low tidal volume (LVT) mechanical ventilation group (LVT group), normal tidal volume (NVT) mechanical ventilation group (NVT group) and high tidal volume (HVT) mechanical ventilation group (HVT group) with 12 rats in each group. After anesthesia, rats in the Sham group were intubated and kept spontaneous breathing. The rats in different tidal volume (VT) groups were mechanically ventilated by endotracheal intubation with VT of 6 mL/kg (LVT group), 10 mL/kg (NVT group), and 20 mL/kg (HVT group), respectively. The inspiration-expiration ratio of the three groups was 1∶1, the ventilation frequency was 40 times/min, and the ventilation time was 3 hours. At the end of the experiment, the bronchoalveolar lavage fluid (BALF) of rats was collected, and the levels of pro-inflammatory factors [tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6)] in BALF were detected by enzyme-linked immunosorbent assay (ELISA). The lung tissues of rats were collected, and the lung wet/dry weight (W/D) ratio was calculated. The pathological changes of lung tissues were observed under light microscopy after hematoxylin-eosin (HE) staining, and lung injury scores were performed. The brain tissue of rats was taken to measure the brain water content, and the Evans blue (EB) content of brain tissue was measured to reflect the permeability of the blood-brain barrier. The tight junction proteins in the brain tissues were detected by Western blotting.Results:After 3 hours of mechanical ventilation, with the increase of VT, the degree of lung injury in VILI rats gradually increased. When VT reached 20 mL/kg, lung tissue structure was significantly injured, alveolar wall edema, alveolar congestion, lung interstitial thickening, a large number of inflammatory cells infiltrated, and the lung injury score, lung W/D ratio, and the levels of TNF-α, IL-1β and IL-6 in BALF were significantly higher than those in the Sham group [lung injury score: 10.6±1.1 vs. 1.4±1.0, lung W/D ratio: 6.6±0.8 vs. 3.7±0.6, TNF-α(ng/L): 832.9±97.9 vs. 103.8±23.3, IL-1β (ng/L): 68.9±14.1 vs. 15.7±2.6, IL-6 (ng/L): 70.8±16.4 vs. 20.3±5.4, all P < 0.05]. Lung injury in rats was accompanied by aggravating brain injury. When VT reached 20 mL/kg, brain water content and EB content in brain tissue were significantly higher than those in the Sham group [brain water content: (85.4±3.6)% vs. (68.7±2.7)%, EB content in brain tissue (μg/g): 887±78 vs. 97±14, both P < 0.05], and the protein expressions of claudin-5, occluding and zonula occluden-1 (ZO-1) in the brain tissue were significantly lower than those in the Sham group [claudin-5 protein (claudin-5/β-actin): 0.67±0.12 vs. 1.45±0.19, occludin protein (occludin/β-actin): 0.48±0.11 vs. 0.99±0.21, ZO-1 protein (ZO-1/β-actin): 0.13±0.03 vs. 0.63±0.12, all P < 0.05]. Conclusion:VILI can induce brain edema and increase blood-brain barrier permeability in rats, which may be related to the down-regulation of tight junction protein expression in the brain tissue.
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Objective:To evaluate the relationship between silent information regulator 1 (SIRT1) and ferroptosis during curcumin-induced reduction of acute lung injury in a mouse model of sepsis.Methods:One hundred and fifty-two SPF-grade male C57BL/6J mice, aged 8 weeks, weighing 23-27 g, were divided into 4 groups ( n=38 each) using a random number table method: sham operation group (C group), sepsis group (S group), curcumin group (Cur group) and curcumin plus SIRT1 inhibitor EX527 group (CE group). Curcumin 200 mg/kg was administered by intragastric gavage every day in Cur group. Curcumin 200 mg/kg was administered by intragastric gavage every day and EX527 5 mg/kg was intraperitoneally injected in CE group. The equal volume of solvent dimethyl sulfoxide (DMSO) was given in C group and S group. Sepsis model was developed by cecal ligation and puncture (CLP) after 5 days of consecutive administration in anesthetized animals. Twenty mice in each group were randomly selected to observe the survival condition within 7 days after CLP. The bronchoalveolar lavage fluid (BALF) was collected at 24 h after developing the model to determine the concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and IL-18 (by enzyme-linked immunosorbent assay), and the lung tissues were obtained for microscopic examination of the pathological changes which were scored and for determination of wet-to-dry lung weight (W/D) ratio, contents of glutathione (GSH), malondialdehyde (MDA) and iron (by colorimetry), and expression of SIRT1, glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long chain family member 4 (ACSL4) (by Western blot). Results:Compared with C group, the 7-day survival rate after CLP was significantly decreased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were increased, the content of GSH in lung tissues was decreased, the contents of MDA and iron were increased, the expression of SIRT1 and GPX4 was down-regulated, and the expression of ACSL4 was up-regulated in S group ( P<0.05). Compared with S group, the 7-day survival rate after CLP was significantly increased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were decreased, the content of GSH was increased, the contents of MDA and iron were decreased, the expression of SIRT1 and GPX4 was up-regulated, and the expression of ACSL4 was down-regulated in Cur group ( P<0.05). Compared with Cur group, the 7-day survival rate after CLP was significantly decreased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were increased, the content of GSH was decreased, the contents of MDA and iron were increased, the expression of SIRT1 and GPX4 was down-regulated, and the expression of ACSL4 was up-regulated in CE group ( P<0.05). Conclusions:The mechanism by which curcumin attenuates acute lung injury may be related to activation of SIRT1 and further inhibition of ferroptosis in mice.
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Objective:To evaluate the effect of open-lung strategy (OLS) on postoperative delirium (POD) in elderly patients undergoing laparoscopic surgery.Methods:Seventy-four elderly patients of both sexes, aged 65-80 yr, with body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective laparoscopic radical rectal cancer or radical prostate cancer surgery under general anesthesia, were divided into 2 groups ( n=37 each) by the random number table method: OLS group and non-OLS (NOLS) group. Patients in OLS group received small tidal volume ventilation, recruitment maneuvers, and individualized positive end-expiratory pressure. Fixed positive end-expiratory pressure 5 cmH 2O was given in NOLS group. Cerebral regional oxygen saturation (rSO 2), pH value, PaO 2, PaCO 2 and PaO 2/FiO 2 were recorded before induction of anesthesia (T 0, baseline value), at 10 min after tracheal intubation (T 1), at 1 and 2 h after pneumoperitoneum (T 2, 3) and at 10 min after extubation (T 4). The levels of serum interleukin-6 (IL-6), IL-10 and calcium-binding protein (S100β) were measured by enzyme-linked immunosorbent assay before surgery, at the end of surgery, and at 1 day after surgery. The development of POD was assessed using the delirium assessment scale at 1-3 days after surgery. Results:Compared with NOLS group, the pH value was significantly decreased at T 3, PaCO 2 was increased, PaO 2, PaO 2/FiO 2 and rSO 2 were increased at T 2-4, serum IL-6 and S100β concentrations were decreased after surgery and at 1 day after surgery, the serum IL-10 concentration was increased, and the incidence of POD was decreased in OLS group ( P<0.05). Conclusions:OLS can increase rSO 2, reduce the systemic inflammatory response, and decrease the risk of POD in elderly patients undergoing laparoscopic surgery.
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Objective:To evaluate the role of monocyte chemoattractant protein-induced protein-1 (MCPIP-1) in acute lung injury in septic rats.Methods:Forty-eight healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 230-270 g, were divided into 6 groups ( n=8 each) using the random number table method: sham operation group (S group), different doses of ubiquitin-proteasome inhibitor groups (M 1 and M 2 groups), cecal ligation and perforation (CLP) group, and different doses of ubiquitin-proteasome inhibitor + CLP groups (M 1-CLP and M 2-CLP group). Sepsis was induced by CLP in anesthetized animals.Ubiquitin-proteasome inhibitor MG-132 5 and 10 mg/kg were intraperitoneally injected at 30 min before sham operation in M 1 and M 2 groups, respectively.MG-132 5 and 10 mg/kg were intraperitoneally injected at 30 min before CLP in M 1-CLP and M 2-CLP groups, respectively.The rats were sacrificed at 6 h after operation, bronchoalveolar lavage (BALF) was collected for determination of the concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 in BALF (by enzyme-linked immunosorbent assay) and lung tissues were obtained for microscopic examination of pathological changes which were scored and for determination of wet/dry lung weight ratio (W/D ratio) and expression of MCPIP-1 protein and mRNA (by Western blot and real-time polymerase chain reaction). Results:Compared with S group, the lung injury scores, W/D ratio, and concentrations of TNF-α, IL-1β and IL-6 in BALF were significantly increased in CLP group ( P<0.05), and no significant changes were found in the parameters mentioned above( P>0.05), and the expression of MCPIP-1 protein and mRNA in lung tissues was significantly up-regulated in M 1 and M 2 groups ( P<0.05), and no significant change was found in the expression of MCPIP-1 protein and mRNA in lung tissues in CLP group ( P>0.05). Compared with CLP group, the lung injury scores, W/D ratio, and concentrations of TNF-α, IL-1β and IL-6 in BALF were significantly decreased, and the expression of MCPIP-1 protein and mRNA in lung tissues was up-regulated in M 1-CLP and M 2-CLP groups ( P<0.05). Conclusions:MCPIP-1 exerts an endogenous protective mechanism during acute lung injury in septic rats.
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Objective:To evaluate the effect of trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) on reflux and micro-aspiration during induction of general anesthesia in the patients undergoing laparoscopic cholecystectomy.Methods:A total of 60 patients, regardless of gender, aged 18-60 yr, with body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective laparoscopic cholecystectomy, were divided into 2 groups ( n=30 each) using a random number table method: routine mask ventilation group (group C) and trans-nasal humidified rapid insufflation ventilatory exchange group (group H). Patients in group C were pre-oxygenated with a mask for 5 min, oxygen flow of 6 L/min and FiO 2 100%, after the induction of anesthesia, the pressure mask was used to artificially assist positive pressure ventilation for 2 min when the patient′s consciousness disappeared, and 2 min later endotracheal intubation was performed.Patients in group H were pre-oxygenated with THRIVE for 5 min, oxygen flow of 30 L/min and FiO 2 100%.The oxygen flow was increased to 50 L/min during anesthesia induction.After anesthesia induction, the oxygen flow was increased to 70 L/min when the patient′s consciousness disappeared, and chin lift and/or jaw thrust was used during apnoea to maintain an open airway, the patient′s mouth was kept closed during the whole process, and 2 min later endotracheal intubation was performed.Ultrasound was used to measure the cross-sectional area (CSA) of the gastric antrum and to monitor the occurrence of gastric insufflation, and the incidence of CSA greater than >3.4 cm 2 was recorded on admission to the operating room and immediately after tracheal intubation.Supraglottic and subglottic secretions were collected at the time of tracheal intubation using visual laryngoscopy after exposing the glottis, and the pepsin content was determined using enzyme-linked immunosorbent assay to assess reflux (content of pepsin in supraglottic secretion >216 ng/ml) and micro-aspiration (content of pepsinin subglottic secretion >200 ng/ml), and arterial blood gas analysis was simultaneously performed.The apnoea time was recorded, and P ETCO 2 at the first mechanical ventilation after tracheal intubation were recorded. Results:Compared with group C, PaO 2 was significantly increased and CSA was decreased immediately after tracheal intubation, and the incidence of CSA greater than >3.4 cm 2 immediately after tracheal intubation was decreased, and the incidence of gastric insufflation, reflux and micro-spiration was decreased, apnoea time was prolonged, and P ETCO 2 at first mechanical ventilation was increased in group H ( P<0.05). Conclusions:THRIVE applied during induction of general anesthesia can reduce the occurrence of reflux and micro-aspiration while ensuring oxygenation in the patients undergoing laparoscopic cholecystectomy.
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Objective:To evaluate the role of silent information regulator 1 (SIRT1) in electroacupuncture (EA)-induced reduction of central post-stroke pain (CPSP) and the relationship with nod-like receptor pyrin domain containing 3 (NLRP3) in rats.Methods:Fifty SPF healthy male Sprague-Dawley rats, aged 6 weeks, weighing 180-220 g, were divided into 5 groups ( n=10 each) using a random number table method: sham operation group (group Sham), CPSP group, CPSP+ sham EA group (group SEA), CPSP+ EA group (group EA) and CPSP+ EA+ SIRT1 inhibitor EX527 group (group EX527). Type Ⅳ collagenase was injected into the right ventral posterolateral nucleus to establish the model of CPSP in CPSP, SEA, EA and EX527 groups.At 24 h after the model was established successfully, 30 min EA (frequency 2/15 Hz) stimulation of Neiguan, Renzhong and Sanyinjiao was performed once a day for 5 consecutive days in EA group.EA was performed at the points 5 mm lateral to the acupoints of Neiguan, Renzhong and Sanyinjiao in group SEA, and the other procedures were similar to those previously described in group EA.SIRT1 inhibitor EX527 5 mg/kg was injected intraperitoneally at 30 min before EA stimulation in group EX527, and the other procedures were similar to those previously described in group EA.At 1 day before the establishment of model (T 0) and at 1, 3 and 5 days after the establishment of model (T 1-3), the thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured.The animals were then sacrificed and brain tissues were taken for determination of the expression of SIRT1, NLRP3 and interleukin (IL)-18 and IL-1β. Results:Compared with Sham group, the TWL was significantly shortened and the MWT was decreased at T 1-3, the expression of SIRT1 was down-regulated, and the expression of NLRP3, IL-18 and IL-1β was up-regulated in CPSP, SEA, EA and EX527 groups ( P<0.05). Compared with CPSP group, the TWL was significantly prolonged and the MWT was increased at T 1-3, the expression of SIRT1 was up-regulated, and the expression of NLRP3, IL-18 and IL-1β was down-regulated in EA group ( P<0.05), and no significant change was found in the parameters mentioned above in group SEA ( P>0.05). Compared with EA group, the TWL was significantly shortened and the MWT was decreased at T 1-3, the expression of SIRT1 was down-regulated, and the expression of NLRP3, IL-18 and IL-1β was up-regulated in EX527 group ( P<0.05). Conclusion:SIRT1 is involved in the process of EA-induced reduction of CPSP, which is related to inhibiting NLRP3 expression in rats.
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Objective:To evaluate the effect of dexmedetomidine on the activity of nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) inflammasome in ventilator-induced lung injury (VILI) in mice.Methods:Eighty-four male SPF C57BL/6J mice, weighing 25-30 g, aged 2-3 months, were divided into 3 groups ( n=28 each) using a random number table method: control group (C group), VILI group and dexmedetomidine group (D group). The mice were tracheostomized and spontaneous breathing was maintained in group C, while the other mice were tracheostomized and mechanically ventilated for 4 h in VILI and D groups.Dexmedetomidine was infused in a loading dose of 1.0μg/kg for 20 min before intubation followed by continuous infusion of 1.0 μg·kg -1·h -1 for 4 h in group D. Blood samples were taken from the femoral artery for blood gas analysis before intubation and at 1, 2 and 4 h of mechanical ventilation (T 1-4), and PaO 2 was recorded for detection of PaO 2.Eight mice were selected at T 4 and sacrificed, and the broncho-alveolar lavage fluid (BALF) was collected for determination of the concentration of total protein, interleukin-1β (IL-1β) and interleukin-18 (IL-18). The lung tissues were removed for microscopic examination of pathologic changes which were scored and for determination of the wet to dry weight (W/D) ratio, expression of IL-1β and IL-18 mRNA (by real-time polymerase chain reaction), and expression of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 (by Western blot). The other 20 mice in each group were observed for the 24-h survival rate. Results:Compared with group C, PaO 2 at T 3 and T 4 and 24-h survival rate were significantly decreased, and the lung injury score, W/D ratio, and concentrations of total protein, IL-1β, and IL-18 in BALF were increased, and the expression of NLRP3, ASC, caspase-1, IL-1β mRNA and IL-18 mRNA was up-regulated in VILI and D groups ( P<0.05). Compared with group VILI, the 24-h survival rate was significantly increased, the lung injury score, W/D ratio, and concentrations of total protein, IL-1β, and IL-18 in BALF were decreased, and the expression of NLRP3, ASC, caspase-1, IL-1β mRNA and IL-18 mRNA was down-regulated in group D ( P<0.05). Conclusion:The mechanism by which dexmedetomidine attenuates VILI may be related to inhibiting NLRP3 inflammasome activity in mice.
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Objective@#To evaluate the role of microRNA-125b (miR-125b) on ventilator-induced lung injury (VILI) in mice.@*Methods@#Forty healthy male C57BL/6 male mice, weighing 25-30 g, aged 2-3 months, were divided into 4 groups (n=10 each) using a random number table method: sham operation group (group Sham), group VILI, VILI plus miR-125b negative control group (group VILI+ NC), and VILI plus miR-125b overexpression group (group VILI+ miR-125b agomir). In VILI+ NC and VILI+ miR-125b agomir groups, miR-125b negative control and miR-125b agomir transfection complex 50 μl were intratracheally instilled, respectively, and 48 h later VILI model was established.The animals were mechanically ventilated for 4 h with high tidal volume (40 ml/kg) to induce VILI.Blood samples were obtained from the femoral artery at 4 h of mechanical ventilation for detection of PaO2, then animals were sacrificed, lungs were removed for determination of wet to dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope), and lung injury was scored.In VILI+ NC and VILI+ miR-125b agomir groups, bronchoalveolar lavage fluid (BALF) was collected to measure the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay.The cell apoptosis of lung tissues was measured using TUNEL, apoptosis index was calculated, the caspase-3 expression was detected by Western blot, and the miR-125b expression was detected by real-time polymerase chain reaction.@*Results@#Compared with Sham group, PaO2 was significantly decreased, and W/D ratio and lung injury score were increased in VILI, VILI+ NC and VILI+ miR-125b agomir groups, and the expression of miR-125b was down-regulated in VILI and VILI+ NC groups (P<0.05). Compared with VILI group, PaO2 was significantly increased, W/D ratio and lung injury score were decreased, the expression of miR-125b was up-regulated (P<0.05), the pathological changes of lung tissues were significantly attenuated in group VILI+ miR-125b agomir, and no significant change was found in the parameters mentioned above in group VILI+ NC (P<0.05). Compared with group VILI+ NC, the concentrations of TNF-α and IL-6 in BALF and apoptotic index were significantly decreased, and the expression of caspase-3 was down regulated in group VILI+ miR-125b agomir (P<0.05).@*Conclusion@#MiR-125b is involved in the endogenous protective mechanism of VILI in mice.
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Objective To evaluate the role of microRNA-125b (miR-125b) on ventilator-induced lung injury (VILI) in mice.Methods Forty healthy male C57BL/6 male mice,weighing 25-30 g,aged 2-3 months,were divided into 4 groups (n=10 each) using a random number table method:sham operation group (group Sham),group VILI,VILI plus miR-125b negative control group (group VILI+NC),and VILI plus miR-125b overexpression group (group VILI+miR-125b agomir).In VILI+NC and VILI+miR-125b agomir groups,miR-125b negative control and miR-125b agomir transfection complex 50 μl were intratracheally instilled,respectively,and 48 h later VILI model was established.The animals were mechanically ventilated for 4 h with high tidal volume (40 ml/kg) to induce VILI.Blood samples were obtained from the femoral artery at 4 h of mechanical ventilation for detection of PaO2,then animals were sacrificed,lungs were removed for determination of wet to dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope),and lung injury was scored.In VILI+NC and VILI+miR-125b agomir groups,bronchoalveolar lavage fluid (BALF) was collected to measure the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay.The cell apoptosis of lung tissues was measured using TUNEL,apoptosis index was calculated,the caspase-3expression was detected by Western blot,and the miR-125b expression was detected by real-time polymerase chain reaction.Results Compared with Sham group,PaO2 was significantly decreased,and W/D ratio and lung injury score were increased in VILI,VILI+NC and VILI+miR-125b agomir groups,and the expression of miR-125b was down-regulated in VILI and VILI+NC groups (P＜0.05).Compared with VILI group,PaO2 was significantly increased,W/D ratio and lung injury score were decreased,the expression of miR-125b was up-regulated (P＜0.05),the pathological changes of lung tissues were significantly attenuated in group VILI+miR-125b agomir,and no significant change was found in the parameters mentioned above in group VILI+NC (P＜0.05).Compared with group VILI+NC,the concentrations of TNF-α and IL-6 in BALF and apoptotic index were significantly decreased,and the expression of caspase-3 was down regulated in group VILI+miR-125b agomir (P＜0.05).Conclusion MiR-125b is involved in the endogenous protective mechanism of VILI in mice.
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Objective To evaluate the accuracy of variation of the end-tidal pressure of carbon dioxide (△PETCO2) in predicting the fluid responsiveness in patients undergoing resection of gastrointestinal tumor.Methods Forty-six patients of both sexes,aged 40-64 yr,with body mass index of 20-24 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective resection of gastrointestinal tumor with general anesthesia,were enrolled in the study.When the change in mean arterial pressure was less than 10％ within 5 min after anesthesia induction,250 ml Ringer's solution was rapidly infused over 10 min via the peripheral vein.Increase in cardiac index after volume expansion ≥ 15％ was considered to be a positive response.The receiver operating characteristic curve for △PETCO2 in determining fluid responsiveness was drawn.Results The results of receiver operating characteristic curve analysis showed that the area under the curve for △PETCO2 in determining fluid responsiveness (95％ confidence interval) was 0.826 (0.730-0.942,P＜0.05),the critical value 21.9％,sensitivity 76.5％,specificity 90.9％.Conclusion △PETCO2 can accurately predict the fluid responsiveness in patients undergoing resection of gastrointestinal tumor.
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Objective To assess the accuracy and feasibility of respirophasic variation in carotid artery blood flow peak velocity (△Vpeak-CA) as predictors of fluid responsiveness in laparoscopic surgery.Methods Fifty-five patients undergoing laparoscopic surgeries,29 males and 26 females,aged 45-75 years,ASA physical status Ⅰ-Ⅲ,with body mass index 20-24 kg/m2,were enrolled.When intra-abdominal pressure was steady at the level of 13-15 mm Hg,6％ hydroxyethylstarch (HES 130/0.4) 500 ml was infused at the speed of 7 ml/kg within 20 minutes.After volume expansion,subjects were classified as responders (group R,n =32) if cardiac index increased (△CI) was≥ 15％ and no responders (group NR,n =23) as △CI＜15％.The receiver operating characteristic curve (ROC) curve for △Vpeak-CA in determining the volume expansion responsiveness was plotted,and the diagnostic threshold was determined.The area under curve (AUC) and 95 ％ confidence interval (CI) was calculated.Cardiac index (CI),△Vpeak-CA and stroke volume variation (SW) were independently recorded at 5 minutes after induction (T1),5 minutes after intra-abdominal pressure were stable at the level of 13-15 mm Hg (T2) and 5 minutes after volume expansion (T3).Results △Vpeak-CA is highly negatively correlated with CI (r=-0.843,P＜0.001).The results of ROC curve analysis showed,△Vpeak-CA threshold discriminated between responders and non-responders with a sensitivity of 81.3％ and a specificity of 91.3％,and the AUC was 0.884 (95％ CI 0.793-0.975).Conclusion △Vpeak-CA seems to be a highly feasible and reliable predictor for fluid responsiveness in laparoscopic surgery patients.
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Objective To evaluate the effect of γ-aminobutyric acid (GABA) preconditioning on pathological stretch-induced damage to type Ⅱ alveolar epithelial cells by mechanical ventilation.Methods A549 cells cultured in vitro (0.2× 106/ml,2.5 ml/well) were randomly divided into 3 groups using a random number table:control group (group C),pathological stretch group (group P) and GABA preconditioning+pathological stretch group (group G).A549 cells were exposed to 20％ cyclic stretch at 0.3 Hz for 6 h in groups P and G;GABA 50 μmol/L was given 30 min before cyclic stretch in group G.After the end of pathological stretch,the cells were collected for determination of the cell viability by methyl thiazolyl tetrazolium assay and lactate dehydrogenase (LDH) release by colorimetricmethod;the expression of F-actin was observed with indirect immunofluorescence;the expression of Rho-associated kinase 1 (ROCK1) and GABAAR were determined by western blot.Results Compared with group C,the cell viability was significantly decreased,the amount of LDH released was increased,the expression of ROCK1 was significantly increased and the expression of GABAAR was significantly decreased in groups P and G (P＜0.05);Compared with group P,the cell viability was significantly increased,the amount of LDH released was decreased,F-actin was re constructed,the expression of ROCK1 was significantly decreased and the expression of GABAAR was significantly increased (P＜0.05) in group G.The reconstruction of F-actin in group P was better than that in group G and worse than that in group C.Conclusion GABA preconditioning can attenuate pathological stretch-induced damage to type Ⅱ alveolar epithelial cells probably through up regulating the expression of GABAA receptor.
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Objective To evaluate the changes in activation of γ?aminobutyric acid(GABA)sig?naling pathway during ventilator?induced brain injury in rats. Methods Thirty?six pathogen?free adult male Sprague?Dawley rats, weighing 280-320 g, were divided into 3 groups(n=12 each)using a random number table: low tidal volume group(LV group), ventilation with high tidal volume for 2 h group(HV1 group)and ventilation with high tidal volume for 6 h group(HV2group). The rats were mechanically ven?tilated for 2 h with the tidal volume set at 10 ml∕kg and the respiratory rate 40 breaths∕min in group LV. The rats were mechanically ventilated for 2 h with the tidal volume set at 40 ml∕kg and the respiratory rate 40 breaths∕min in group HV1. The rats were mechanically ventilated for 6 h with the tidal volume set at 40 ml∕kg and the respiratory rate 40 breaths∕min in group HV2. Blood samples were collected at the end of ven?tilation for determination of serum neuron?specific enolase(NSE)and S100β protein concentrations by en?zyme?linked immunosorbent assay. Six rats were then sacrificed and their brains were removed for determi?nation of interleukin?1β(IL?1β)and tumor necrosis factor?α(TNF?α)contents(by enzyme?linked im?munosorbent assay)and expression of glutamic acid decarboxylase(GAD)and GABAAreceptors(by Western blot). Morris water maze test was performed on 2nd day after the end of ventilation. Results Compared with group LV, the serum concentrations of NSE and S100β protein and contents of IL?1β and TNF?α were significantly increased, the expression of GAD and GABAAreceptors was up?regulated, the es?cape latency was prolonged, and the percentage of swimming distance at the original platform was decreased in HV1and HV2groups(P<0.05). Compared with group HV1, the serum concentrations of NSE and S100β protein and contents of IL?1β and TNF?α were significantly increased, the expression of GAD and GABAAreceptors was up?regulated, the escape latency was prolonged, and the percentage of swimming distance at the original platform was decreased in group HV2(P<0.05). Conclusion Activation of GABA signaling pathway is enhanced during ventilator?induced brain injury, which may be involved in the patho?physiological mechanism of ventilator?induced brain injury in rats.
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Objective To evaluate the effects of lung-protective ventilation on the cerebral oxygen metabolism and postoperative cognitive function in elderly patients requiring one-lung ventilation (OLV).Methods Sixty patients of both sexes,aged 65-80 yr,weighing 45-75 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective radical resection for esophageal cancer performed via video-assisted thoracoscope with general aneshesia,were divided into 2 groups (n =30 each)using a random number table:volume-controlled ventilation group (group VCV) and protective ventilation group (group PV).In group VCV,the tidal volume (VT) was set at 10 ml/kg during two-lung ventilation (TLV) and at 7 ml/kg during OLV.In group PV,the VT was set at 7 ml/kg during TLV and at 5 ml/kg during OLV with positive end-expiratory pressure of 5 cmH2O,and lung recruitment maneuver was performed every 45 min with inspiratory pressure at 15,20 and 25 cmH2O,PEEP 5 cmH2O,3 breaths per pressure,5 s/breath.Before induction of anesthesia (T1),at 10 min of TLV (T2),at 30 min of OLV (T3) and at 15 min after restoration of TLV (T4),blood samples were taken from the radial artery and jugular bulb for blood gas analysis,and pH value,arterial oxygen partial pressure (PaO2),arterial carbon dioxide partial pressure (PaCO2),arterial oxygen saturation (SaO2) and jugular venous oxygen saturation (SjvO2) were recorded.Oxygenation index (OI),intrapulmonary shunt (Qs/Qt),arteriovenous blood O2 content difference (Da-jvO2) and cerebral O2 extraction rate (CERO2) were calculated at the same time.Cognitive function was assessed using Mini-Mental State Examination at 7 days and 1 month after operation,and the development of postoperative cognitive dysfunction was recorded.Results PaO2,DajvO2,CERO2 and Qs/Qt were significantly higher and SjvO2 and OI were lower at T2-4 than at T1 in two groups (P＜0.05).PaO2,SjvO2 and OI were significantly lower and Qs/Qt and CERO2 were higher at T3 than at T2,and Da-jvO2 was higher at T3-4 than at T2 in two groups (P＜0.05).Compared with group VCV,PaO2,PaCO2,SjvO2 and OI were significantly increased and Qs/Qt,Da-jvO2 and CERO2 were decreased at T3,the Mini-Mental State Examination scores were increased on postoperative day 7,and the incidence of postoperative cognitive dysfunction was decreased in group PV (P＜O.05).Conclusion Lungprotective ventilation is helpful in improving postoperative brain function of elderly patients requiring OLV.
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Objective To evaluate the effect of lung protective ventilation strategy on inflammatory responses in brain tissues of elderly patients requiring one-lung ventilation (OLV) during radical resection for esophagus cancer.Methods Sixty patients of both sexes,aged 65-80 yr,weighing 45-75 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective radical resection for esophageal cancer,were divided into volume-controlled ventilation (VCV) group (n =30) and VCV plus protective ventilation strategy group (PV group,n =30) using a random number table.In group VCV,the tidal volume was set at 10 ml/kg during two-lung ventilation (TLV) and at 7 ml/kg during OLV with inspiratory/expiratory ratio 1:2.In group PV,the tidal volume was set at 7 ml/kg during TLV and at 5 ml/kg during OLV with inspiratory/expiratory ratio 1:2 and positive end-expiratory pressure 5 cmH2O,and lung recruitment maneuver was performed every 45 min.End-tidal pressure of carbon dioxide was maintained at 35-45 mmHg,and bispectral index value at 40-60 in both groups.Before induction of anesthesia (T1),at 10 min of TLV (T2),at 30 min of OLV (T3),at 15 min after restoration of TLV (T4) and at 24 h after operation (T5),jugular bulb venous blood samples were taken for determination of serum glial fibrillary acid protein,tumor necrosis factor-α and interleukin-6 concentrations by enzyme-linked immunosorbent assay.The cognitive function was assessed using Mini-Mental State Examination before operation (T0),at T5 and at 3 and 7 days after operation (T6,7).The occurrence of postoperative delirium was recorded.Results Compared with group VCV,the serum concentrations of tumor necrosis factor-α,interleukin-6 and glial fibrillary acid protein were significantly decreased at T3-5,Mini-Mental State Examination scores were increased at T6,7,and the incidence of postoperative delirium was decreased in group PV (P＜0.05).Conclusion The mechanism by which lung protective ventilation strategy decreases the development of postoperative cerebral dysfunction is related to reduction of inflammatory responses in brain tissues of elderly patients requiring OLV during radical resection for esophagus cancer.
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Objective To evaluate the effect of ulinastatin on γ-aminobutyric acid (GABA) signal pathway in mice with ventilator-induced lung injury (VILI).Methods Thirty-six male Wister mice were randomly divided into 3 groups using a random number table:control group (group C), ventilator-induced lung injury group (group VILI),and ventilator-induced lung injury+ ulinastatin group (group UTI),n =12 in each group.VILI was induced by 4 h mechanical ventilation with tidal volume 40 ml/kg in groups VILI and UTI.Ulinastatin 1×10 5 U/kg was injected intraperitoneally 1 h before ventilation in group UTI,while the equal volume of normal saline was given in groups C and VILI.The mice were then sacrificed,the left lung was lavaged,and broncho-alveolar lavage fluid (BALF)was collected for determination of concentrations of protein,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and intercellular adhesion molecule-1 (ICAM-1).The lung tissues were re-moved for determination of the wet to dry lung weight (W/D)ratio,the mRNA expression level of IL-1β,TNF-αand ICAM-1.The pathological changes of the lungs were determined under light micro-scope and the lung injury scores were also determined.Immunohistochemistry and Western blot were used to detected the protein expression level of GAD and GABAA R.Results The W/D ratio (6.7 ± 2.4 vs.8.5±2.3)and lung scores [(6.9±2.3)scores vs.(1 1.8±2.7)scores]were significantly de-creased in group UTI than those in group VILI.The concentrations of IL-1β[(56±1 1)ng/L vs.(77 ±1 5)ng/L],TNF-α[(105±29)ng/L vs.(1 58±37)ng/L]and ICAM-1 [(205±46)ng/L vs.(293 ±61)ng/L]in BALF in group UTI were significantly decreased than those in group VILI.The mRNA ex-pression levels of IL-1β(1.81±0.26 vs.2.58±0.34),TNF-α(1.61±0.15 vs.2.94±0.27)and ICAM-1 (1.74±0.27 vs.2.79±0.31)were significantly decreased in group UTI than those in group VILI.The protein expression levels of GAD (0.44±0.08 vs.0.18 ±0.04)and GABAA R (0.30 ±0.09 vs.0.15 ± 0.04)were significantly increased in group UTI than those in group VILI.Conclusion Ulinastatin can at-tenuate VILI probably through activating GABA signaling pathway.
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Objective To evaluate the effect of mechanical stretch preconditioning on pathological stretch-induced activation of γ-aminobutyric acid (GABA) signaling pathway in human type Ⅱ alveolar epithelial cells (AEC Ⅱ).Methods AEC Ⅱ cell line (A549 cells) culturedin vitro were divided into control group (group C), pathological stretch group (group P1) and mechanical stretch preconditioning group (group P2). In group C, A549 cells were cultured routinely. In group P1, A549 cells were exposed to 20% cyclic stretch for 6 hours. In group P2, A549 cells were exposed to 5% cyclic stretch for 60 minutes, and then exposed to 20% cyclic stretch for 6 hours. The cells were harvested for determination of the cell viability by methyl thiazolyl tetrazolium assay, lactate dehydrogeuase (LDH) release was determined by colorimetric method, the levels of interleukin (IL-1β and IL-6) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA), the mRNA expressions of IL-1β, IL-6 and TNF-α were determined by reverse transcription-polymerase chain reaction (RT-PCR), and the protein expressions of glutamic acid decarboxylase (GAD) and γ-aminobutyric acid A receptor (GABAAR) were determined by Western Blot.Results Compared with group C, the cell viability of group P1 was significantlydecreased (A value: 0.196± 0.071 vs. 0.886±0.107), the release rate of LDH was significantly increased [(12.3±2.4)% vs. (1.9±0.5)%]; the contents and mRNA expressions of IL-1β, IL-6 and TNF-α in cell culture medium were significantly increased [IL-1β (ng/L): 138.6±19.7 vs. 32.7±7.4, IL-6 (ng/L): 196.5±31.7 vs. 55.4±13.8, TNF-α (ng/L): 111.3±21.8 vs. 20.8±7.6; IL-1β mRNA (2-ΔΔCT): 2.79±0.44 vs. 0.83±0.12, IL-6 mRNA (2-ΔΔCT): 1.99±0.25 vs. 0.56±0.11, TNF-α mRNA (2-ΔΔCT): 2.54±0.37 vs. 0.72±0.09]; the protein expressions of GAD and GABAAR were significantly decreased [GAD (gray value): 0.38±0.12 vs. 1.75±0.45, GABAAR (gray value): 0.29±0.09 vs. 1.68±0.39; allP < 0.05]. Compared with group P1, the cell viability of group P2 was significantly increased (A value: 0.523±0.132 vs. 0.196±0.071),the release rate of LDH was significantly decreased [(6.9±1.7)% vs. (12.3±2.4)%]; the contents and mRNA expressions of IL-1β, IL-6 and TNF-α in cell culture medium were significantly decreased [IL-1β (ng/L): 79.2±11.6 vs. 138.6±19.7, IL-6 (ng/L): 89.6±15.6 vs. 196.5±31.7, TNF-α (ng/L): 55.9±11.4 vs. 111.3±21.8; IL-1β mRNA (2-ΔΔCT): 1.92±0.36 vs. 2.79±0.44, IL-6 mRNA (2-ΔΔCT): 1.09±0.18 vs. 1.99±0.25, TNF-α mRNA (2-ΔΔCT): 1.77±0.25 vs. 2.54±0.37]; the protein expressions of GAD and GABAAR were significantly increased [GAD (gray value): 1.26±0.33 vs. 0.38±0.12, GABAAR (gray value): 1.04±0.15 vs. 0.29±0.09; allP < 0.05]. Conclusion The mechanism by which mechanical stretch preconditioning attenuates pathological stretch-induced injury in human AECⅡ is related to the activation of GABA signaling pathway.
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Objective To evaluate the relationship between the shedding of syndecan-4(SDC-4) in lung tissues and ventilator-induced lung injury in rats. Methods Thirty pathogen-free healthy adult male Wistar rats, weighing 220-250 g, were divided into 3 groups(n=10 each)using a random number table:control group(group C), mechanical ventilation with traditional tidal volume(VT)group(group T-VT) and mechanical ventilation with high VTgroup(group H-VT). The animals were anesthetized with pento-barbital sodium and tracheostomized. The rats kept spontaneous breathing in group C. The rats were me-chanically ventilated for 4 h with the VTset at 6 ml∕kg in group T-VT and with the VTset at 40 ml∕kg in group H-VT. Blood samples were collected immediately after the end of ventilation for measurement of serum SDC-4 concentrations by enzyme-linked immunosorbent assay. The left lung was lavaged, and broncho-alveolar lavage fluid was collected for determination of interleukin-1beta(IL-1β), IL-18, tumor necrosis factor-alpha and SDC-4 concentrations by enzyme-linked immunosorbent assay. The lungs were removed for determination of the wet to dry weight ratio and expression of SDC-4 protein and mRNA in lung tissues(by Western blot and real-time polymerase chain reaction, respectively)and for examination of the pathological changes. The lung injury scores were recorded. Results Compared with group C, the wet to dry weight ratio, lung injury scores, concentrations of IL-1β, IL-18, tumor necrosis factor-alpha and SDC-4 in bron-cho-alveolar lavage fluid and concentrations of SDC-4 in serum were significantly increased, the expression of SDC-4 mRNA was up-regulated, and the expression of SDC-4 was down-regulated in group H-VT(P<005), and no significant change was found in the parameters mentioned above in group T-VT(P>005).Marked pathological changes of lung tissues were found in group H-VT. Conclusion A large shedding of SDC-4 in lung tissues may be involved in the pathophysiological mechanism of ventilatior-induced lung injury in rats.
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Objective To evaluate the accuracy of respirophasic variation in carotid artery blood flow peak velocity(ΔVpeak-CA)in predicting fluid responsiveness in the patients undergoing surgery in the prone position. Methods Forty-three American Society of Anesthesiologists physical status Ⅰ-Ⅲ pa-tients of both sexes, aged 45-75 yr, with body mass index of 20-25 kg∕m2, scheduled for elective posteri-or approach lumbar surgery, were enrolled in the study.After induction of anesthesia, hydroxyethyl starch 130∕0.4 sodium chloride injection 7 ml∕kg was intravenously infused over 20 min when the patients were in the prone position.Subjects were classified as responders if stroke volume index increased≥15% after vol-ume expansion.The receiver operating characteristic curve for ΔVpeak-CA in determining positive fluid re-sponsiveness was drawn. Results The results of receiver operating characteristic curve analysis showed that: the cut-off value of ΔVpeak-CA in predicting positive fluid responsiveness was 7.94%, sensitivity 81.8%, specificity 70.0%, and the area under the curve(95% confidence interval)was 0.818 (0.378-0.757). Conclusion Respirophasic ΔVpeak-CA can accurately predict fluid responsiveness in the patients undergoing surgery in the prone position.
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Objective To evaluate the effect of dexmedetomidine on the expression of gamma-aminobutyric acid(GABAA)receptors during ventilator-induced lung injury(VILI)in rats. Methods Thirty pathogen-free adult male Sprague-Dawley rats,weighing 280-320 g,were divided into 3 groups(n=10 each)using a random number table:control group(group C),group VILI and dexmedetomidine group(group Dex).The rats were mechanically ventilated for 4 h with the tidal volume of 40 ml/kg to establish VILI model. Dexmedetomidine 50 μg/kg was injected intraperitoneally after the rats were anesthetized in group Dex,while the equal volume of normal saline was given instead in C and VILI groups. The animals were sacrificed at 4 h of mechanical ventilation,the lungs were removed for examination of pathological changes which were scored,bronchoalveolar lavage fluid(BALF)was collected for determination of concentrations of total protein,interleukin-1 beta(IL-1β),IL-6 and tumor necrosis factor-alpha(TNF-α),and the lung specimens were obtained for determination of the wet/dry weight ratio(W/D ratio),alveolar fluid clearance(AFC)and expression of GABAA receptors,IL-1β,IL-6 and TNF-α mRNA in lung tissues. Results Compared with group C,the W/D ratio,pathological scores,expression of total protein,IL-1β,IL-6 and TNF-α in BALF and expression of IL-1β,IL-6 and TNF-α mRNA in lung tissues were significantly increased,and the GABAA receptor expression and AFC were decreased in VILI and Dex groups(P<0.05).Compared with group VILI,the W/D ratio,pathological scores,expression of total protein,IL-1β,IL-6 and TNF-α in BALF and expression of IL-1β,IL-6 and TNF-α mRNA in lung tissues were significantly decreased,and the GABAA receptor expression and AFC were increased in group Dex(P<0.05).Conclusion The mechanism by which dexmedetomidine reduces VILI is related to up-regulation of GABAA receptor expression in rats.