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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 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 open-lung strategy (OLS) on cardiopulmonary function in frail elderly patients undergoing laparoscopic surgery.Methods:Eighty-four frail elderly patients aged 65-80 yr, with body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists physical status Ⅱor Ⅲ, with preoperative Fried frailty phenotype scale score ≥3, undergoing elective laparoscopic radical rectal cancer or radical prostate cancer surgery under general anesthesia, were divided into 2 groups ( n=42 each) by the random number table method: OLS group and non-OLS group (NOLS group). The patients underwent recruitment maneuvers and individualized positive end-expiratory pressure (PEEP) in OLS group, while patients received fixed PEEP (5 cmH 2O) in NOLS group.At 10 min after endotracheal intubation (T 0, baseline value), immediately after the peak of recruitment maneuvers (T 1), 30 min (T 2) and 1 h (T 3) after individualized PEEP setting and 10 min before the end of surgery (T 4), cardiac function indexes were measured by transoesophageal echocardiography, optic nerve sheath diameter was measured, and the arterial blood gas analysis indexes and pulmonary function indexes were recorded.The levels of serum cardiac troponin T, creatine kinase-MB and precursor of type B natriuretic peptide were determined by chemiluminescence before surgery and at 1 and 2 days after surgery.The postoperative pulmonary complications within 7 days after surgery and postoperative outcomes were also recorded. Results:Eighty-one patients were finally enrolled, with 41 in NOLS group and 40 in OLS group.Compared with NOLS group, the left ventricular end diastolic area, left ventricular ejection fraction, stroke volume, ratio of early mitral flow velocity to early mitral annulus velocity, mitral annular plane systolic excursion, left ventricular global longitudinal strain, right ventricular end diastolic area, right ventricular fractional area change, tricuspid annular plane systolic excusion and right ventricular global longitudinal strain were significantly decreased at T 1, 2 ( P<0.05), and no significant change was found in the indices mentioned above at the remaining time points ( P>0.05), PaO 2, oxygenation index, and lung compliance were increased at T 1-4, PaCO 2 and alveolar arterial partial pressure difference of oxygen were decreased, the total incidence of pulmonary complications was reduced within 7 days after operation, and the duration of postanesthesia care unit stay, time to first out-of-bed activity and postoperative length of hospital stay were shortened ( P<0.05), and no significant change was found in optic nerve sheath diameter and concentrations of serum cardiac troponin T, creatine kinase-MB, and precursor of type B natriuretic peptide at each time point in OLS group ( P>0.05). Conclusions:OLS can improve lung function in frail elderly patients, which is helpful for patient prognosis without causing negative cardiac effects, and can be safely used for intraoperative airway management in frail elderly patients without obvious cardiac dysfunction.