雷公藤红素对小鼠盐酸吸入导致的急性肺损伤的保护机制的研究

发布时间：2018-01-27 03:06

本文关键词： 盐酸吸入急性肺损伤雷公藤红素　出处：《青岛大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:围术期急性肺损伤/急性呼吸窘迫综合症是临床常见的肺部并发症,胃内容物误吸是其中的主要原因之一。对于此类急性肺损伤,目前主要是通过给氧、机械通气等呼吸支持措施治疗以及糖皮质激素药物治疗,然而疗效均不满意。本研究试图通过观察预先使用药物雷公藤红素对盐酸吸入性肺损伤是否具有保护作用,以其为临床治疗提供理论依据,进而探讨雷公藤红素对小鼠盐酸吸入性急性肺损伤的保护机制。方法:将24只健康清洁级小鼠按随机数字表法分成4组(n=6):A组,正常对照组;B组,雷公藤红素腹腔给药组;C组,盐酸吸入性急性肺损伤组;D组:盐酸吸入性急性肺损伤+雷公藤红素腹腔给药组。四组小鼠预先连续3天腹腔注射药物处理:A组和C组每天用3ml/kg生理盐水腹腔内注射,B组和D组用雷公藤红素3mg/kg(约为3ml/kg)腹腔注射,每天一次。实验开始时四组小鼠禁食12h但不禁水,用戊巴比妥钠(50mg/kg)腹腔注射麻醉,用24号套管针的外套管进行气管插管,操作成功后C组和D组气管内先注射盐酸(PH=1.5,2ml/kg),然后注入少许空气使药液完全进入肺内制作小鼠肺损伤模型;A组和B组注射等量生理盐水和空气。然后拔除气管插管由小鼠自主呼吸空气,并允许小鼠自由接触水和食物。采用气管内滴注盐酸的方法制备小鼠吸入性急性肺损伤模型。于滴注后6 h时处死小鼠取肺组织,观察小鼠盐酸吸入6 h后肺组织病理切片,测定肺组织匀浆中超氧化物岐化酶(SOD)活力与丙二醛(MDA)含量,并检测肺组织中肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)含量的变化以及巨噬细胞移动抑制因子(MIF)和髓过氧化物酶(MPO)的改变。结果:1、肺组织病理学结果显示:与C组相比,D组肺组织结构清晰,肺间质肿胀、炎性细胞浸润及出血明显减轻。2、与A组相比,C组、D组MDA值升高(P0.01),SOD活力降低(P0.01),且C组MDA值比D组高(P0.01),SOD活力比D组低(P0.01)。3、TNF-α、IL-6含量均以A组和B组为低,C组为最高,D组居中。与A组相比,C组、D组TNF-α值、IL-6值均升高(P0.01),且C组TNF-α值、IL-6值均高于D组(P0.01)/4、MIF、MPO含量以A组和B组为低,C组为最高,D组居中。与A组相比,C组、D组MIF值、MPO值均升高(P0.01),且C组MIF值、MPO值均高于D组(P0.01)。结论:1.盐酸吸入可引起肺弥漫性急性损伤,表现为呼吸急促、氧分压下降,肺组织病理改变。2.盐酸吸入导致的急性肺损伤/急性呼吸窘迫综合征通过促进肺组织的脂质过氧化反应,破坏氧化-抗氧化平衡以及产生大量炎症因子TNF-a、IL-6而造成。3.雷公藤红素对小鼠盐酸吸入性急性呼吸窘迫综合征有保护作用,其机制可能与其抑制肺组织炎症因子TNF-a、IL-6的产生和释放,抑制脂质过氧化反应,提高抗氧化能力、以及抑制肺组织MIF表达、减少中性粒细胞浸润有关。
[Abstract]:Objective: perioperative acute lung injury / acute respiratory distress syndrome (ARDS) is a common pulmonary complication, and gastric misprision is one of the main causes. Respiratory support measures such as mechanical ventilation and glucocorticoid therapy. However, the curative effect is not satisfactory. This study attempts to observe the protective effect of tripterygium tripterygium on inhaled hydrochloric acid lung injury in order to provide theoretical basis for clinical treatment. To explore the protective mechanism of tripterygium wilfordii on acute lung injury induced by hydrochloric acid inhalation in mice methods: 24 healthy and clean grade mice were randomly divided into 4 groups (n = 4) and normal control group (n = 6: a). Group B, Tripterygium wilfordii intraperitoneal administration group; Group C: acute lung injury induced by hydrochloric acid inhalation; Group D: Tripterygium wilfordii was administered intraperitoneally with hydrochloric acid inhaled acute lung injury. Four groups of mice were intraperitoneally injected with 3 ml / kg physiological saline for 3 ml / kg per day for 3 consecutive days. Group B and group D were intraperitoneally injected with tripterine 3 mg / kg (about 3 ml / kg) once a day. At the beginning of the experiment, the mice of the four groups fasted for 12 hours but could not help drinking water. 50 mg / kg pentobarbital sodium was used intraperitoneally to anesthetize and endotracheal intubation was performed with the outer tube of cannula 24. After successful operation, PH1.5 hydrochloride was injected into the trachea of group C and group D. Then a little air was injected into the lung to make the model of lung injury in mice. Group A and group B were injected with the same amount of saline and air. Then tracheal intubation was pulled out and the air was breathed autonomously by the mice. Mice were given free access to water and food. The model of acute lung injury was established by intratracheal instillation of hydrochloric acid. The mice were killed at 6 h after infusion. The pathological sections of lung tissue were observed after inhalation of hydrochloric acid for 6 h, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the homogenate of lung tissue were determined. The changes of tumor necrosis factor- 伪 (TNF- 伪) and interleukin-6 (IL-6) in lung tissue and the changes of macrophage migration inhibitory factor (MIF) and myeloperoxidase (MPO) were also detected. Change. Result: 1. The results of lung histopathology showed that compared with group C, lung tissue structure was clear, interstitial swelling, inflammatory cell infiltration and hemorrhage were significantly alleviated in group D, and group C was significantly less than group A. The activity of MDA in group D was higher than that in group D, and the activity of MDA in group C was higher than that in group D, and the activity of MDA in group C was lower than that in group D. The content of TNF- 伪 IL-6 in group A and group B was the highest in group C, and the TNF- 伪 value in group D was higher than that in group A (P 0.01). Moreover, the level of TNF- 伪 and IL-6 in group C was higher than that in group D (P 0.01 / 4). The MPO content in group A and group B was the highest in group C, and the highest in group D, and in comparison with group A, group C was higher than that in group A. The MIF value of group D was higher than that of group D (P 0.01), and the value of MIF in group C was higher than that of group D (P 0.01). Conclusion: 1. Inhaled hydrochloric acid can induce diffuse acute lung injury. Acute lung injury / acute respiratory distress syndrome induced by inhalation of hydrochloric acid promotes lipid peroxidation in lung tissue. Tripterygium tripterygium has protective effect on acute respiratory distress syndrome induced by hydrochloric acid. The mechanism may be related to the inhibition of the production and release of TNF-a IL-6, the inhibition of lipid peroxidation, the enhancement of antioxidant capacity, and the inhibition of MIF expression in lung tissue. The decrease of neutrophil infiltration is related to.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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