摘要
目的 探讨盐酸戊乙奎醚对油酸致急性呼吸窘迫综合征(ARDS)大鼠的抗炎作用.方法 按随机数字表法将30只成年雄性SD大鼠均分为对照组、模型组及治疗组.各组大鼠均经股静脉置管,对照组注入生理盐水1.1 mL/kg;模型组注射0.1 mL/kg油酸后随即注入生理盐水1.0 mL/kg;治疗组注入0.1 mL/kg油酸后随即注入1.0 mL/kg盐酸戊乙奎醚.制模后3 h,对各组大鼠进行血气分析,计算氧合指数(PaO2/FiO2),用酶联免疫吸附试验(ELISA)测定血清白细胞介素(IL-1、IL-6)含量;处死大鼠取肺组织,计算肺湿/干重(W/D)比值,镜下观察肺组织形态学改变;用比色法测定超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量;免疫组化法检测肺组织肿瘤坏死因子-α(TNF-α)表达.Pearson相关分析肺W/D比值与各指标的相关性.结果 与对照组比较,模型组大鼠PaO2/FiO2明显下降,肺W/D比值明显升高,血清IL-1、IL-6水平及肺组织MDA含量显著升高,肺组织SOD活性明显下降;光镜下可见肺泡腔内大量渗出液、中性粒细胞和红细胞,肺泡间隔明显增宽、水肿;电镜下可见Ⅱ型肺泡上皮细胞板层小体变性、局部破坏及排空现象明显;免疫组化显示,肺组织TNF-α阳性表达明显增多.与模型组比较,治疗组PaO2/FiO2明显改善〔mmHg(1 mmHg=0.133 kPa):204.42±31.61比113.91±47.78,P〈0.05〕,肺W/D比值明显降低(5.80±0.44比6.82±0.59,P〈0.01),血清IL-1、IL-6水平及肺组织MDA含量明显下降〔IL-1(μg/L):18.38±0.28比20.04±0.39,IL-6(μg/L):12.64±0.67比14.28±1.33,MDA(nmol/mg):3.95±0.28比5.17±0.29,均P〈0.05〕,肺组织SOD活性明显升高(U/mg:48.75±2.41比45.09±1.69,P〈0.01),组织形态学及病理学改变明显减轻,肺组织中TNF-α阳性表达明显减少〔阳性细胞率:(25.80±3.44)%比(38.82±3.59)%,P〈0.01〕.结论 盐酸戊乙奎醚通过降低肺W/D比值,抑制氧化应激和炎症反应来有效改善油酸致ARDS大鼠的氧合、肺损伤及肺水肿程度.
Objective To investigate the anti-inflammatory effect of penehyclidine hydrochloride on oleic acid-induced acute respiratory distress syndrome (ARDS) in rats.Methods According to randomize number table method, 30 adult male Sprague-Dawley (SD) rats were divided into control group, model group and treatment group. Catheters were placed in femoral vein in each group. The control group was injected with 1.1 mL/kg physiological saline; the model group was injected with 0.1 mL/kg oleic acid and then injected with 1.0 mL/kg normal saline to establish ARDS model; the treatment group was injected with 0.1 mL/kg oleic acid and then injected with 1.0 mL/kg penehyclidine hydrochloride. At 3 hours after the model was established, blood gas analysis was carried out in each group, oxygenation index (PaO2/FiO2) was calculated, and the levels of serum interleukins (IL-1, IL-6) were measured by enzyme linked immunosorbent assay (ELISA). Rats were sacrificed to harvest lung tissue, and the lung wet/dry ratio (W/D) was calculated; the morphological changes of lung tissue was observed under microscope; the superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by colorimetry; the expression of tumor necrosis factor-α(TNF-α) in lung tissue was detected by immunohistochemical method. The correlations between lung W/D ratio and various indicators were analyzed using Pearson correlation test.Results Compared with the control group, PaO2/FiO2 in model group was significantly decreased, lung W/D ratio was significantly increased, serum IL-1, IL-6 levels and lung tissue MDA content were significantly increased, lung tissue SOD activity was significantly decreased; the alveolar space was filled with exudate, neutrophils and red blood cells, and there were obvious edema and broadening in pulmonary interstitial and alveolar under light microscope; the type Ⅱ alveolar epithelial cells were partly destroyed, accompanied by lamellar body degeneration and emptying phenomenon under electron microscope; and immunohistochemistry showed that the positive expression of TNF-α in lung tissue was significantly increased. Compared with the model group, PaO2/FiO2 in the treatment group was significantly improved [mmHg (1 mmHg = 0.133 kPa): 204.42±31.61 vs. 113.91±47.78,P 〈 0.05], the lung W/D ratio was significantly decreased (5.80±0.44 vs. 6.82±0.59,P 〈 0.01), serum IL-1, IL-6 levels and lung tissue MDA content were significantly decreased [IL-1 (μg/L): 18.38±0.28 vs. 20.04±0.39, IL-6 (μg/L): 12.64±0.67 vs. 14.28±1.33, MDA (nmol/mg): 3.95±0.28 vs. 5.17±0.29, allP 〈 0.05], the activity of SOD in lung tissue was significantly increased (U/mg: 48.75±2.41 vs. 45.09±1.69,P 〈 0.01), histological and pathological changes were significantly reduced, and the positive expression of TNF-α in lung tissue was significantly reduced [positive cell rate: (25.80±3.44)% vs. (38.82±3.59)%,P 〈 0.01].Conclusion Penehyclidine hydrochloride can effectively improve the oxygenation, alleviate lung injury and reduce pulmonary edema in oleic acid induced ARDS rat by decreasing lung W/D ratio, inhibiting oxidative stress and inflammatory response.
作者
许惠仙
谢晶
类延娜
崔青松
金明根
Xu Huixian;Xie Jing;Lei Yanna;Cui Qingsong;Jin Minggen(Department of Intensive Care Unit,Yanbian University Affiliated Hospital,Yanji 133000,Jilin,China;Department of Intensive Care Unit,Shuyang Hospital of Traditional Chinese Medicine,Suqian 223600,Jiangsu,China)
出处
《中华危重病急救医学》
CAS
CSCD
北大核心
2018年第8期764-767,共4页
Chinese Critical Care Medicine
关键词
盐酸戊乙奎醚
急性呼吸窘迫综合征
油酸
氧化应激
炎症反应
Penehyelidine hydrochloride
Acute respiratory distress syndrome
Oleie acid
Oxidativestress
Inflammatory reaction