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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 ventilation with different positive end-expiratory pressures (PEEPs) on intracranial pressure in the patients undergoing gynecological laparoscopic surgery.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 25-55 yr,with body mass index of 18-27 kg/m2,scheduled for elective gynecological endoscopic surgery,were divided into 3 groups (n=20 each) using a random number table method:routine ventilation group (group A),4 cmH2O PEEP group (group B) and 8 cmH2O PEEP group (group C).The patients were mechanically ventilated with PEEP 4 or 8 cmH2O at 5 min of head-down tilt after start of pneumoperitoneum in group B and group C.The patients were mechanically ventilated in volume-controlled mode,with tidal volume 7 ml/kg,inspired oxygen concentration 50％ and inspiratory/expiratory ratio 1 ∶ 2.Blood samples were collected from the radial artery for measurement of PaCO2 and PaO2 at 5 min after tracheal intubation (T0),5,15 and 30 min of head-down tilt (T1-3),and 5 min of the supine position after the end of pneumoperitoneum (T4).The peak airway pressure (Ppeak) was recorded,dynamic pulmonary compliance (Cdyn)was calculated,and optic nerve sheath diameter was measured using an ultrasonic apparatus at T0-4.Cognitive function was assessed at 1 day before surgery and 7 days after surgery using Mini-Mental State Examination.Results Compared with group A,Ppeak was significantly increased at T1-4,and PaO2 was increased at T2 in group B,and Ppeak and PaO2 were increased at T1-4,and Cdyn was increased at T1,2 in group C (P＜0.05).Compared with group B,Ppeak was significantly increased at T4,and Cdyn was increased at T2 in group C (P＜0.05).There was no significant difference in optic nerve sheath diameter or Mini-Mental State Examination score at each time point among three groups (P＞0.05).No patients developed cognitive dysfunction at 7 days after surgery in three groups.Conclusion Ventilation with different PEEPs causes no increase in intracranial pressure of the patients undergoing gynecological laparoscopic surgery.