出 处:《西北药学杂志》2023年第2期118-122,共5页Northwest Pharmaceutical Journal
基 金:2018年度河南省医学科技攻关计划项目(编号:2018010050)。
摘 要:目的 探讨七氟醚对急性肺损伤(acute lung injury, ALI)大鼠肺组织形态学、氧合指数、肺组织氧化应激和炎症介质的影响。方法 将40只SD大鼠按体质量随机数字表法分为对照组,ALI组,低、高剂量七氟醚组,除对照组外,各组经气管滴注脂多糖(lipopolysaccharide, LPS)5 mg·kg^(-1)制备ALI大鼠模型,对照组给予等体积生理盐水,低、高剂量七氟醚组于造模前30 min分别吸入体积分数为1.2%、2.4%的七氟醚,LPS滴注完成后12 h进行肺湿/干质量比(wet/dry weight ratio, W/D)、氧合指数检测,HE染色观察肺组织病理形态学变化,酶联免疫法检测肺组织乳酸脱氢酶(lactate dehydrogenase, LDH)、超氧化物岐化酶(superoxide dismutase, SOD)、丙二醛(malondialdehyde, MDA)、髓过氧化物酶(myeloperoxidase, MPO)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,L^(-1)β)和Toll样受体4(Toll-like receptor 4,TLR4)水平。结果 ALI组大鼠W/D和肺损伤评分明显高于对照组(P<0.05),氧合指数明显低于对照组(P<0.05);低、高剂量七氟醚组大鼠W/D和肺损伤评分明显低于ALI组(P<0.05),氧合指数明显高于ALI组(P<0.05)。对照组肺组织结构清晰且间质无扩张、出血和炎症浸润,肺泡壁无增厚现象,肺泡间隙清晰;ALI组肺间质、肺泡腔存在炎症细胞浸润,有肺泡塌陷、出血和肺泡间隔增厚现象;七氟醚组肺损伤情况较ALI组得到明显改善。ALI组大鼠MPO、LDH、MDA、TNF-α、IL-6、IL^(-1)β和TLR4水平明显高于对照组(P<0.05),SOD水平低于对照组(P<0.05);七氟醚组大鼠MPO、LDH、MDA、TNF-α、IL-6、IL^(-1)β和TLR4水平明显低于ALI组(P<0.05),SOD水平明显高于ALI组(P<0.05)。结论 七氟醚预干预可以改善ALI大鼠肺损伤病理形态学变化,提高氧合指数,还可降低肺组织氧化应激和炎症反应,可能与调节TLR4的表达有关。Objective To explore the effects of sevoflurane on lung tissue morphology, oxygenation index, oxidative stress and inflammatory mediators in lung tissues of rats with acute lung injury(ALI).Methods According to random number table method, 40 SD rats were divided into control group, ALI group, low-dose and high-dose sevoflurane groups. Except for the control group, the other groups were given intratracheal instillation of lipopolysaccharide(LPS, 5 mg·kg^(-1)) to prepare ALI rat models, while the control group were given the same volume of normal saline. At 30 minutes before modeling, low-dose and high-dose sevoflurane groups were given 1.2% and 2.4% sevoflurane for inhalation, respectively. 12 hours later after LPS instillation, lung wet/dry weight ratio(W/D) and oxygenation indexes were detected. The pathological morphology changes of lung tissues were observed by HE staining. The levels of lactate dehydrogenase(LDH), superoxide dismutase(SOD), malondialdehyde(MDA), myeloperoxidase(MPO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), interleukin-1β(IL^(-1)β) and Toll-like receptor 4(TLR4) in lung tissues were detected by enzyme-linked immunosorbent assay.Results The W/D and lung injury scores in ALI group were significantly higher than those in control group(P<0.05), while the oxygenation index was significantly lower than that in control group(P<0.05). The W/D and lung injury scores in low-dose and high-dose sevoflurane groups were significantly lower than those in ALI group(P<0.05), while the oxygenation index was significantly higher than that in ALI group(P<0.05). In control group, the structure of lung tissues was clear, there was no interstitial expansion, hemorrhage, inflammation infiltration or thickening of alveolar walls, and alveolar gap was clear. In ALI group, there was inflammatory cells infiltration in lung interstitium and alveolar cavity, alveolar collapse, hemorrhage and thickening of alveolar septum. Compared with ALI group, the lung injury was significantly improved in sevoflurane g
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