右美托咪定预处理对急性肺损伤保护的实验研究

发布时间：2019-04-19 21:55

【摘要】：目的:利用脂多糖（LPS）诱导建立大鼠急性肺损伤模型，观察α2受体激动剂——右美托咪定预先给药后，各组血气分析，肺组织病理变化及肺组织匀浆MPO活性和肺湿干重比，血清细胞因子TNF-α和IL-6变化的情况，探讨右美托咪定预先给药对大鼠急性肺损伤（ALI）的保护作用。方法:经气管滴注LPS5mg/kg，建立大鼠ALI模型。45只250~300g雄性SD大鼠，按随机数字表法分为3组，每组15只：生理盐水组(NS组，，单纯输注生理盐水)、肺损伤组（ALI组，腹腔注射等剂量生理盐水，30min后气管滴注LPS)、右美托咪定预先给药组(Dex组，腹腔注射右美托咪定50μg/kg，30min后气管滴注LPS)。滴注LPS后6h再次腹腔注射水合氯醛麻醉大鼠，开腹腹主动脉取血，离心检测血清中肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)，并行动脉血气分析。随后放血处死大鼠，开胸取出肺组织，留取左上肺叶立刻放入液氮冷冻，制备成组织匀浆，检测肺组织髓过氧化物酶(MPO)活性。右肺叶用于肺湿干重比(W/D)的测定，左下肺用于病理学检查，光镜下观察肺组织病理学改变。结果:①肺组织大体观，NS组大鼠肺组织呈淡粉红色，表面光滑触之弹性较好，无水肿及出血灶；ALI组大鼠肺组织呈现暗红色弹性较差，肺包膜下可见广泛出血点；Dex组大鼠可见肺组织色泽暗红，有散在出血点但较LPS组少。②光镜下，ALI组肺泡壁增厚，肺泡结构紊乱，肺间隔断裂，中性粒细胞弥漫浸润，肺泡腔内出现大量水肿液，亦可见红细胞漏出；Dex组的病理改变较ALI组轻。③ALI组大鼠肺组织W/D和MPO活性水平明显增高，与NS组相比差异有统计学意义(P0.05)，Dex组肺组织W/D和MPO活性水平与ALI组相比明显下降，差异有统计学意义(P0.05)。④ALI动脉血氧分压与NS组相比明显降低，Dex组动脉血氧分压较ALI组升高，差异均有统计学意义(P0.05)。⑤与NS组比较，ALI组和Dex组中血清TNF-α和IL-6浓度显著升高(P0.05)，与ALI组比较，Dex组中血清TNF-α和IL-6浓度明显降低(P 0.05)。结论:右美托咪定预先给药对LPS诱导大鼠急性肺损伤有一定的保护作用，与抑制中性粒细胞在肺内聚集、激活和TNF-α、IL-6等炎性因子的释放有关。
[Abstract]:Objective: to establish a rat model of acute lung injury induced by lipopolysaccharide (LPS). To observe the changes of blood gas, pathological changes of lung tissue, the activity of MPO in lung homogenate and the ratio of wet to dry weight of lung after preadministration of 伪 2 receptor agonist, right metomide. The changes of serum cytokines TNF- 伪 and IL-6 were studied in order to investigate the protective effect of right metomidine on (ALI) in rats with acute lung injury. Methods: a rat model of ALI was established by intratracheal infusion of LPS5mg/kg,. Forty-five male SD rats were randomly divided into three groups, 15 rats in each group: normal saline group (NS group, infused saline alone), lung injury group (ALI group, n = 15), control group (n = 15). After intraperitoneal injection of equal dose of normal saline, LPS), was injected into the trachea of the Dex group (Dex group), and LPS). Was injected into the trachea after intraperitoneal injection of 50 渭 g / kg,30min of right metametridamidine (LPS).) in the trachea of the 30min group (Dex group). The rats were anesthetized with chloral hydrate again 6 hours after infusion of LPS. The blood was collected from the open abdominal aorta. The serum levels of tumor necrosis factor-伪 (TNF- 伪) and interleukin-6 (IL-6) were detected by centrifugation, and the blood gas analysis was performed. Then the rats were killed by bloodletting, the lung tissue was removed from the chest, and the left upper lung lobe was immediately frozen with liquid nitrogen to prepare tissue homogenate, and the activity of myeloperoxidase (MPO) in lung tissue was measured. The right lobe was used to measure the wet-dry-weight ratio (WW) of the lung, the left lower lung was used for pathological examination, and the pathological changes of the lung tissue were observed under light microscope. Results: (1) the lung tissue of NS group was light pink, smooth touch elasticity was better, no edema and bleeding foci were found in the lung tissue of ALI group, dark red elasticity was poor in the lung tissue of the ALI group, and extensive bleeding spots were found under the lung capsule. In Dex group, the lung tissue was dark red in color, scattered in bleeding point but less than that in LPS group. 2 under light microscope, alveolar wall thickened, alveolar structure disorder, pulmonary septum broken, neutrophil diffuse infiltration, and plenty of edema fluid appeared in alveolar cavity in ALI group. Red blood cell leakage was also observed. The pathological changes in the Dex group were lighter than those in the ALI group, and the levels of WFD and MPO activity in the lung tissue in the 3ALI group were significantly higher than those in the NS group (P 0.05), and the levels of WFD and MPO activity in the lung tissue in the), Dex group were significantly lower than those in the ALI group. (4) the partial pressure of arterial oxygen in Ali group was significantly lower than that in NS group, and the partial pressure of arterial oxygen in Dex group was significantly higher than that in ALI group (P0.05). 5 compared with NS group, the partial pressure of arterial oxygen in Ali group was significantly higher than that in NS group (P0.05). The levels of serum TNF- 伪 and IL-6 in ALI group and Dex group were significantly higher than those in ALI group (P0.05). Compared with ALI group, the serum TNF- 伪 and IL-6 concentrations in Dex group decreased significantly (P0.05). Conclusion: pre-administration of dexmetomidine has some protective effects on LPS-induced acute lung injury in rats, which is related to the inhibition of neutrophil aggregation, activation and the release of inflammatory factors such as TNF- 伪, IL-6 and so on.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614

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