【作者】 林慧庆；

【导师】 黄杰；

【作者基本信息】 武汉大学 ， 外科学， 2004， 硕士

【摘要】 目的：比较硝酸银和滑石粉浆在大鼠自发性气胸模型中产生胸膜固定术的效果；探讨TNF-α、ICAM-1和NF-κB在硝酸银和滑石粉浆诱导的胸膜固定术中的作用及产生胸膜固定术的机制。 方法：健康成年雄性Sprague-Dawley大鼠66只，随机分为正常对照组(6只)、滑石粉T组(30只)和硝酸银A组(30只)。建立大鼠气胸模型，正常对照组胸腔内注入0.9％生理盐水，A组注入硝酸银(0.1％硝酸银1ml)，T组注入200mg／kg滑石粉+1.0ml 0.9％生理盐水。A组和T组分别在第1d、4d、7d、2w、4w时，进行剖胸探查收集标本，观察大鼠胸膜粘连积分、胸膜炎性积分、胸膜纤维化积分及检测肺组织中髓过氧化物酶(MPO)的活性；ELISA法检测24小时收集的血清和胸液中TNF-α的含量及各时点血清中TNF-α的含量；观察肺组织病理学改变及检测肺组织中NF-κB及ICAM-1的活性。 结果：滑石粉浆组产生胸膜粘连在初期较硝酸银组快，但从第二周开始，硝酸银组产生胸膜粘连效果好于滑石粉浆组，到第四周，滑石粉浆组粘连积分为1.8±0.1，而硝酸银组积分为3.3±0.2，显著高于滑石粉浆组；炎性积分和纤维化积分均为硝酸银组高于滑石粉浆组，两组肺组织内MPO活性随着注入硬化剂的时间延长而逐渐增加，其活性均在注入硬化剂后开始增高，第二周时达到高峰值，到第四周时降至正常水平。硝酸银组24小时胸液量多于滑石粉浆组；两组肺组织内ICAM-1和NF-κB活性表达随着注入硬化剂的时间延长而逐渐增加，其活性均在注入硬化剂后开始增高，第二周时达到高峰值，到第四周时降至正常水平，且肺组织内ICAM-1和NF-κB活性有明显的相关性。血清中各观察时点TNF-α的含量均为滑石粉浆组高于硝酸银组，但两组24小时胸液中TNF-α的含量均高于血清中的含量，且在硝酸银组中显著增高。 结论：0.1％硝酸银1ml产生胸膜固定术的效果好于200mg／kg滑石粉，具有临床使用价值。TNF-α是炎症前细胞因子，对滑石粉浆和硝酸银所致的胸膜粘连起关键性作用；NF-κB的激活和ICAM-1的表达增强了胸膜粘连的作用。胸膜固定术的主要机制是无菌性炎症反应以及炎性细胞的豁附过程。更多还原

【Abstract】 Objective: To study the mechanisms of experimental pleurodesis in rats induced by silver nitrate or talc, and the role of TNF- a, ICAM-1 and NF- kB in the mechanisms of experimental pleurodesis in rats induced by silver nitrate or talc. To compare the pleurodesis results from the intrapleural injection of silver nitrate and talc slurry over an observation period of one month in rats.Methods: 66 Adult Sprague-Dawley rats underwent pleurodesis as follows: 6 rats received 1ml 0.9% Natrii Chloride solution; 30 rats received 1ml of 0.1% silver nitrate; and 30 rats received 200mg/kg of talc slurry in 1 ml intrapleurally. Six rats in each group were killed at day1, day4, day7, day 14 and day28 after intrapleural injection. The degree of gross pleurodesis, the amount of microscopic pleural fibrosis and inflammation were graded on a scale of 0 to 4. Pleural fluid at the first 24 hours, hisopathological alternation of experimental lung were observed. TNF-a in plasma and 24h pleural fluid were determined by ELISA. The NF-kB activation and ICAM-1 expression of the experimental lung tissues were examined by immunohistochemistry and image analysis. The accumulation of polymorphonuclear leukocytes in lung tissues was determined by the myeloperoxidase(MPO) assay.Results: The mean+SEM gross pleurodesis score in the rats that received silver nitrate was 3.3+0.2, which was significantly higher than the score of 1.8+0.1 in the rats that received talc. The mean gross pleurodesis score was significantly higher at each of the observation times(P<0.05), except at the first seven days, in the rats that received silver nitrate. The NF- kB activation and ICAM-1 expression were both positive staining in the cytoplasm for each observation times of two groups. They began to increase at the dayl and peak at the week2, and then decreased gradually to the contrast level at the week4. The ICAM-1 expression was positively correlated with the NF- k B activation in lung tissues. The MPO activation began to increase at the dayl and peak at the week2, and then decreased gradually to the contrast level at the week4, and was significantly higher (P<0.05) in the rats that received silver nitrate at each of the observation times. So does the microscopic pleural fibrosis and inflammation grades. The volume of pleural fluid at 24h following silver nitrate administration were significant higher thanthat of talc, while the TNF-a in plasma were on the contrary. The TNF-a in 24h plasma were significant lower in 24h pleural fluid at the same experimental group. Conclusion: The intrapleural injection of 1ml of 0.1% silver nitrate produces a better pleurodesis than does the intrapleural injection of 200mg/kg of talc slurry in rats. The up-regulation of NF- k B activation and ICAM-1 expression is important in the process of pleurodesis. TNF- a is important in the process of pleurodesis. The mechanisms responsible for the pleurodesis is that the inflammatory reaction to the administration of sclerosing agent. The efficacy of silver nitrate as a sclerosing agent in humans should be evaluated.更多还原