【摘要】：目的:利用脂多糖（LPS）誘導(dǎo)建立大鼠急性肺損傷模型，觀察α2受體激動(dòng)劑——右美托咪定預(yù)先給藥后，各組血?dú)夥治�，肺組織病理變化及肺組織勻漿MPO活性和肺濕干重比，血清細(xì)胞因子TNF-α和IL-6變化的情況，探討右美托咪定預(yù)先給藥對(duì)大鼠急性肺損傷（ALI）的保護(hù)作用。 方法:經(jīng)氣管滴注LPS5mg/kg，建立大鼠ALI模型。45只250~300g雄性SD大鼠，按隨機(jī)數(shù)字表法分為3組，每組15只：生理鹽水組(NS組，，單純輸注生理鹽水)、肺損傷組（ALI組，腹腔注射等劑量生理鹽水，30min后氣管滴注LPS)、右美托咪定預(yù)先給藥組(Dex組，腹腔注射右美托咪定50μg/kg，30min后氣管滴注LPS)。滴注LPS后6h再次腹腔注射水合氯醛麻醉大鼠，開(kāi)腹腹主動(dòng)脈取血，離心檢測(cè)血清中腫瘤壞死因子-α(TNF-α)和白介素-6(IL-6)，并行動(dòng)脈血?dú)夥治�。隨后放血處死大鼠，開(kāi)胸取出肺組織，留取左上肺葉立刻放入液氮冷凍，制備成組織勻漿，檢測(cè)肺組織髓過(guò)氧化物酶(MPO)活性。右肺葉用于肺濕干重比(W/D)的測(cè)定，左下肺用于病理學(xué)檢查，光鏡下觀察肺組織病理學(xué)改變。 結(jié)果:①肺組織大體觀，NS組大鼠肺組織呈淡粉紅色，表面光滑觸之彈性較好，無(wú)水腫及出血灶；ALI組大鼠肺組織呈現(xiàn)暗紅色彈性較差，肺包膜下可見(jiàn)廣泛出血點(diǎn)；Dex組大鼠可見(jiàn)肺組織色澤暗紅，有散在出血點(diǎn)但較LPS組少。②光鏡下，ALI組肺泡壁增厚，肺泡結(jié)構(gòu)紊亂，肺間隔斷裂，中性粒細(xì)胞彌漫浸潤(rùn)，肺泡腔內(nèi)出現(xiàn)大量水腫液，亦可見(jiàn)紅細(xì)胞漏出；Dex組的病理改變較ALI組輕。③ALI組大鼠肺組織W/D和MPO活性水平明顯增高，與NS組相比差異有統(tǒng)計(jì)學(xué)意義(P0.05)，Dex組肺組織W/D和MPO活性水平與ALI組相比明顯下降，差異有統(tǒng)計(jì)學(xué)意義(P0.05)。④ALI動(dòng)脈血氧分壓與NS組相比明顯降低，Dex組動(dòng)脈血氧分壓較ALI組升高，差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。⑤與NS組比較，ALI組和Dex組中血清TNF-α和IL-6濃度顯著升高(P0.05)，與ALI組比較，Dex組中血清TNF-α和IL-6濃度明顯降低(P 0.05)。 結(jié)論:右美托咪定預(yù)先給藥對(duì)LPS誘導(dǎo)大鼠急性肺損傷有一定的保護(hù)作用，與抑制中性粒細(xì)胞在肺內(nèi)聚集、激活和TNF-α、IL-6等炎性因子的釋放有關(guān)。
[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 偽 2 receptor agonist, right metomide. The changes of serum cytokines TNF- 偽 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-偽 (TNF- 偽) 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- 偽 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- 偽 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- 偽, IL-6 and so on.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R614

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