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右美托咪定对慢性阻塞性肺疾病大鼠机械通气期间肺组织氧化应激及炎症反应的影响

Effects of dexmedetomidine on oxidative stress and inflammatory response in lungs during mechanical ventilation in COPD rats.

作者信息

Li Pengcheng, Han Jing, Zhang Dan, Cao Shu, Su Chunyu

机构信息

Department of Anesthesiology, The First Hospital of Qiqihar, Qiqihar, Heilongjiang 161000, P.R. China.

Department of Anesthesiology, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang 161000, P.R. China.

出版信息

Exp Ther Med. 2020 Feb;19(2):1219-1224. doi: 10.3892/etm.2019.8341. Epub 2019 Dec 17.

Abstract

Effects of dexmedetomidine (Dex) on oxidative stress and inflammatory response in lungs during mechanical ventilation in chronic obstructive pulmonary disease (COPD) rats were investigated. Eleven out of 38 SD rats were randomly selected as the blank control group, and the other 27 rats were subjected to modeling. After the modeling, 11 rats in the blank control group and 11 rats randomly selected from the model group received non-invasive test for lung function. Three rats from the blank control group and 3 rats from the model group were selected for hematoxylin and eosin (HE) staining to confirm successful modeling, and the other 24 rats were randomly divided into 3 groups, 8 rats in each group, including model control, Dex low-dose and Dex high-dose group. A COPD rat model was established by passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Each group underwent mechanical ventilation for 2 h. The Dex low-dose group and Dex high-dose group were intravenously administered at 1.0 µg/kg/h and 5.0 µg/kg/h of Dex, and the other two groups received intravenous drip of the same amount of normal saline. Blood gas analysis was performed to calculate carbon dioxide partial pressure (PaCO), oxygen partial pressure (PaO) and blood pH. HE staining was performed to analyze pulmonary pathological features of COPD rat model. Serum inflammatory factors interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were detected by ELISA, and the levels of antioxidant enzymes superoxide dismutase 2 (SOD2) and catalase were analyzed by western blot analysis. After 28 days of modeling, TV, PEF, FEV0.3 and FEV0.3/FVC decreased significantly in the COPD model group. HE staining showed that in the model group, the alveolar cells became larger, the alveolar wall became thinner, and some alveolar walls were even broken. The lung lobule showed obvious cell degeneration, necrosis and shedding, and the interstitial inflammatory cell infiltration, suggesting that the COPD rat model was successfully established. After 2 h of mechanical ventilation and Dex intravenous infusion, PaCO decreased, PaO increased, and blood pH value increased (p<0.05). Inflammatory factors IL-8 and TNF-α decreased (p<0.05). Oxidative stress index MDA also decreased (p<0.05), antioxidant enzymes SOD2 and catalase increased (p<0.05). Dexmedetomidine can improve the oxidative stress response during mechanical ventilation in rats with COPD, and can reduce the inflammation of lung tissue, thus protecting the lung tissue of COPD rats.

摘要

研究了右美托咪定(Dex)对慢性阻塞性肺疾病(COPD)大鼠机械通气期间肺组织氧化应激和炎症反应的影响。38只SD大鼠中随机选取11只为空白对照组,其余27只进行造模。造模后,空白对照组的11只大鼠和从模型组中随机选取的11只大鼠接受肺功能无创检测。从空白对照组和模型组分别选取3只大鼠进行苏木精-伊红(HE)染色以确认造模成功,其余24只大鼠随机分为3组,每组8只,包括模型对照组、Dex低剂量组和Dex高剂量组。通过被动吸烟和气管内滴注脂多糖建立COPD大鼠模型。每组进行2小时的机械通气。Dex低剂量组和Dex高剂量组分别以1.0μg/kg/h和5.0μg/kg/h的剂量静脉注射Dex,另外两组静脉滴注等量的生理盐水。进行血气分析以计算二氧化碳分压(PaCO)、氧分压(PaO)和血液pH值。进行HE染色以分析COPD大鼠模型的肺病理特征。通过酶联免疫吸附测定(ELISA)检测血清炎症因子白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)和丙二醛(MDA),并通过蛋白质免疫印迹分析检测抗氧化酶超氧化物歧化酶2(SOD2)和过氧化氢酶的水平。造模28天后,COPD模型组的潮气量(TV)、呼气峰流速(PEF)、第0.3秒用力呼气容积(FEV0.3)和FEV0.3/用力肺活量(FVC)显著降低。HE染色显示,模型组中肺泡细胞变大,肺泡壁变薄,部分肺泡壁甚至破裂。肺小叶呈现明显的细胞变性、坏死和脱落,以及间质炎症细胞浸润,表明成功建立了COPD大鼠模型。机械通气2小时并静脉输注Dex后,PaCO降低,PaO升高,血液pH值升高(p<0.05)。炎症因子IL-8和TNF-α降低(p<0.05)。氧化应激指标MDA也降低(p<0.05),抗氧化酶SOD2和过氧化氢酶升高(p<0.05)。右美托咪定可改善COPD大鼠机械通气期间的氧化应激反应,并可减轻肺组织炎症,从而保护COPD大鼠的肺组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ff4/6966231/47aee9e32473/etm-19-02-1219-g00.jpg

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