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| 七氟醚减轻大鼠呼吸机相关性肺损伤 |
| Sevoflurane alleviated ventilator-induced lung injury in rats |
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| DOI：10.12089/jca.2022.06.014 |
| 中文关键词: 七氟醚 呼吸机相关性肺损伤 NF-E2相关因子2 NOD样受体热蛋白结构域相关蛋白3 氧化应激 炎症 大鼠 |
| 英文关键词: Sevoflurane Ventilator-induced lung injury NF-E2-related factor 2 NOD-like receptor pyrin domain containing 3 Oxidative stress Inflammation Rats |
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| 中文摘要: |
目的 探讨七氟醚对大鼠呼吸机相关性肺损伤（VILI）的影响并探讨其可能机制。
方法 健康SPF级雄性SD大鼠36只，6～8周龄，体重220～280 g。随机分为三组：对照组（C组）、VILI组（V组）和七氟醚组（S组），每组12只。大鼠给予1%戊巴比妥钠40 mg/kg麻醉后行气管切开插管术，C组自主呼吸4 h，V组和S组插管后机械通气4 h，S组机械通气期间吸入2%七氟醚4 h。通气参数：VT 20 ml/kg，RR 80次/分，I∶E 1∶1，FiO2 21%，PEEP 0 cmH2O。机械通气结束时采集股动脉血测定PaO2。处死大鼠，取肺组织和支气管肺泡灌洗液（BALF），计算肺组织湿/干重比值（W/D），采用ELISA法检测BALF中白细胞介素（IL）-1β、IL-18浓度，二氯荧光黄双乙酸盐法检测BALF中肺泡巨噬细胞活性氧（ROS）水平，Western blot法及qRT-PCR法检测肺组织NF-E2相关因子2（Nrf2）、NLRP3、凋亡相关斑点样蛋白（ASC）、caspase-1蛋白含量及其mRNA表达量，观察肺组织病理学改变并进行肺损伤评分。
结果 与C组比较，V组和S组机械通气结束时PaO2、肺组织Nrf2蛋白含量及其mRNA表达量明显降低（P<0.05），肺组织W/D、BALF中IL-1β、IL-18浓度、BALF中肺泡巨噬细胞ROS水平、肺组织NLRP3、ASC、caspase-1蛋白含量及其mRNA表达量、肺损伤评分明显升高（P<0.05）。与V组比较，S组机械通气结束时PaO2、肺组织Nrf2蛋白含量及其mRNA表达量明显升高（P<0.05），肺组织W/D、BALF中IL-1β、IL-18浓度、BALF中肺泡巨噬细胞ROS水平、肺组织NLRP3、ASC、caspase-1蛋白含量及其mRNA表达量、肺损伤评分明显降低（P<0.05）。
结论 七氟醚可能通过上调Nrf2和下调NLRP3炎性小体的表达，减轻肺组织氧化应激反应和炎症反应，减轻大鼠呼吸机相关性肺损伤。 |
| 英文摘要: |
Objective To evaluate the effects of sevoflurane on ventilator-induced lung injury (VILI) in rats and its possible mechanism.
Methods Thirty-six specific pathogen-free (SPF) healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 220-280 g, were randomly divided into three groups: control group (group C), VILI group (group V) and VILI combined with sevoflurane group (group S), 12 rats in each group. All rats in the three groups were anesthetized with 1% pentobarbital sodium 40 mg/kg and intubated with tracheotomy. Group C maintained spontaneous respiration for 4 hours, group V and group S were treated with mechanical ventilation for 4 hours, group S inhaled 2% sevoflurane for 4 hours during mechanical ventilation. Ventilation parameters were set up as the following: tidal volume 20 ml/kg, respiratory rate 80 breaths/minutes, inspiratory/expiratory ratio 1∶1, fraction of inspired oxygen 21%, positive end-expiratory pressure 0 cmH2O. Blood samples of femoral artery were collected immediately for the detection of PaO2 at the end of mechanical ventilation. The rats were sacrificed, then lung tissue samples and bronchoalveolar lavage fluid (BALF) were collected respectively, and wet/dry weight ratio (W/D) of lung tissue was calculated. The concentrations of interleukin (IL)-1β and IL-18 in BALF were determined by enzyme-linked immunosorbent assay (ELISA). The level of reactive oxygen species (ROS) in alveolar macrophages in BALF was detected by DCFH-DA. The expression of NF-E2-related factor 2 (Nrf2), NOD-like receptor pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 protein and mRNA in lung tissues were detected by Western blot and qRT-PCR. Lung histopathological changes were observed and lung injury scores were recorded.
Results Compared with group C, PaO2 at the end of mechanical ventilation and the expression of Nrf2 protein and mRNA in lung tissues in groups V and S were significantly decreased (P < 0.05), W/D of lung tissue, the concentrations of IL-1β and IL-18 in BALF, ROS level in alveolar macrophages in BALF, NLRP3, ASC, and caspase-1 protein expression and mRNA in lung tissues, and lung injury score in groups V and S were significantly increased (P < 0.05). Compared with group V, PaO2 at the end of mechanical ventilation and the expression of Nrf2 protein and mRNA in lung tissues in group S were significantly increased (P < 0.05), W/D of lung tissue, the concentrations of IL-1β and IL-18 in BALF, ROS level in alveolar macrophages in BALF, NLRP3, ASC, and caspase-1 protein expression and mRNA in lung tissues, and lung injury score in group S were significantly decreased (P < 0.05).
Conclusion Sevoflurane may alleviate VILI in rats by up-regulating Nrf2 and down-regulating NLRP3 inflammasome expression, reducing lung tissue oxidation and inflammatory response. |
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